A Brief Introduction of transcontinnental railroad

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sequenceforEcoli：对大肠杆菌序列

Solutions Systems Microbiology 1.084J/20.106J PROBLEM SET #3Problem 3.1a.Describe the stringent response, and at what level and what components of cellular activity it regulates.The stringent response is triggered in response to two modified nucleotides called alarmones—guanosinetetraphostpate (ppGpp) and guanosine pentaphosphate (pppGpp). These nucleotides accumulate rapidly duringa shift-down from amino acid excess to starvation and are synthesized by an STP-dependent protein, RelA thatis associated with the ribosomal 50S subunit. These alarmones have global control effects that inhibit rRNA and tRNA synthesis, and thus adjust the cell’s biosynthesis in response to amino acid limitation.b.Most biosynthetic operons need only be under negative control for effective regulation, while mostcatabolic operons need to be under both negative and positive control. Why might this be?Biosynthetic operons normally require only negative control for effective regulation because the cell only needs to know when there is “enough” of that biosynthetic product for growth. Catabolic operons, on the other hand, have to be regulated both positively and negatively, since these operons provide the ATP for biosynthesis, and also the carbon intermediates for biosynthesis.c.Why are promoters from E. coli under positive control not close matches to the promoter consensussequence for E. coli?If a promoter closely matches the DNA consensus sequence one would expect RNA polymerase to bind to that promoter and induce transcription in the absence of other factors. Therefore, promoters under positive control would be expected to be quite different.d.The attenuation control of some of the pyrimidine biosynthetic pathway genes in E. coli actually involvescoupled transcription and translation. Can you propose a mechanism whereby the cell could somehowmake use of translation to help it measure the level of pyrimidine nucleotides?If there were a shortage of pyrimidine nucleotides, one would expect transcription to go more slowly. Such a system might include a termination loop that forms unless the ribosome is closely following the RNA polymerase.When polymerase is functioning at maximal rates, it moves out ahead of the ribosome, allowing the termination loop to form. When transcription slows because of pyrimidine shortage, the ribosome follows RNA polymerase closely enough so that the loop does not form.e. How could quorum sensing be considered a regulatory mechanism for conserving cell resources?Quorum sensing systems can be considered a regulatory mechanism for conserving cell resources is that the genes under its control are all induced at the same times in response to cell density, and conditions that enhance productive use of those resources. For example, pathogenesis in many Pseudomonas aerugenosa requires high cell densities for invasion and colonization, and also for production of biofilms that increase pathogenicity and protect the cells from antibiotics.Problem 3.2a.How does homologous recombination differ from site-specific recombination?Homologous recombination refers to recombination involving extensive homology between two regions of DNA.In site-specific recombination, a site on the DNA, usually a few base pairs in length, is recognized by a specific protein and results in recombination between two DNA molecules that often do not share homology.b.What does an F+ cell need to do before it can transfer chromosomal genes?Before a donor cell can transfer chromosomal genes it must initiate DNA replication and continue DNA synthesis during transfer.c.What do you think are the most useful transposons for isolating a variety of bacterial mutants? Why aresuch transposons so useful for this purpose?Transposons containing antibiotic resistance genes are useful for obtaining a variety of mutants since theintroduction of the transposons into a population of cells allows the use of antibiotic selection to identify viable cells containing the transposon while counter selecting against those cells not stably integrating the transposon.d.Describe why the discovery and use of transformation and the use of the F plasmid were importantmilestones in the history of genetics. What insights did they contribute?Transformation experiments lead to proof that DNA was the genetic material. F plasmids allow for chromosomal mapping.e.Describe three different ways that foreign DNA can enter the cell. How can homologous recombinationfavor the integration of more than a single or a few genes into the chromosome?Conjugation--Direct cell-to-cell transfer of plasmid DNA through pili or channels between bacteria.Transduction--Transfer of DNA mediated by independently replicating bacterial viruses (bacteriophages).Bacteriophages have variations in specificity, but typically DNA transferred via transduction is among closely related bacteria.Transformation--Uptake of naked DNA from the environment either naturally (via transport proteins) or artificially (electroporation, or other methods of making holes in cell walls).Homologous recombination requires sequence homology, thus with prokaryotes this is likely to be triggered by multiple genes.Problem 3.3a.Explain why in generalized transduction one always refers to a transducing particle but in specializedtransduction one refers to a transducing virus or phage.Generalized transduction refers to the “accidental”, random incorporation of host DNA into the virus particle.Thus, in a given population of phage particles, only a few will contain host DNA. For this reason, the particles are called transducing particles. Specialized transduction involves a mutant phage that has lost some of its original DNA and has picked up a specific fragment of host genetic material. In a suspension of a specialized transducing phage, essentially all of the virus particles will contain the transduced gene.b.What are the essential characteristics of a cloning vector? What characteristics of plasmids make themespecially useful as vectors for molecular cloning? What characteristic(s) of the F plasmid makes it lessuseful for use in vitro?The essential characteristics of a cloning vector are 1) small size making DNA isolation and manipulation easier,2) independent origin of replication, 3) multiple copy number allowing for amplification of cloned DNA, and 4)selectable markers for identification of the cells containing the cloning vector or recombinant clone.Characteristics that make plasmids especially useful for molecular cloning (including those just stated) include 1)a polylinker, or multiple cloning site, 2) color selection for immediate identification of recombinant plasmids, and3) promoters for expression of the cloned gene. (e.g. M13 phage promoters for generation of single-strandedDNA, etc). The F plasmid is much too large to be useful as a cloning vector and does not contain any selectable markers.c.What are the general properties of insertion elements? Class II transposons?Insertion elements (or sequences) have no genes other than hose required for them to move to a new location.They are ~1000bp in length and become interated at specific sites on the genome (both plasmids andchromosomal DNA, and a few bacteriophages). Homologous recombination often occurs between IS elements causing the integration of new DNA. Transposons are larger than IS elements and contain other genes such as antibiotic resistance. Conjugative transposons are able to move between bacterial species via conjugation, not solely around in one genome.Problem 3.4Five Hfr strains A through E are derived from a single F+ strain of E. coli. The following table shows the time of entry (in minutes) of the first 5 genetic markers observed in interrupted mating experiments. Please answer a-c, below, based on the data.STRAIN A STRAIN B STRAIN C STRAIN D STRAIN Emal+ 1 ade+ 3 pro+ 3 pro+10 his+7str s11 his+28 met+29 gal+16 gal+17ser+16 gal+32 xyl+32 his+26 pro+23ade+36 pro+44 mal+37 ade+41 met+49his+51 met+70 str s47 ser+61 xyl+52a)Draw a map of the F+ plasmid, showing the positions of all the genes relative to the origin, andtheir distance apart in minutes.See figure.b)Show the insertion point and orientation of each Hfr strain.See figure.c)In using each of these strains, which gene would you chose to use as a marker, to get the greatestnumber of “exconjugants” (eg. recipient cells that have successfully received an F plasmid)?In each strain one should use the last gene to be expressed to ensure that the full plasmid is present.Thus Strain A = xyl, Strain B = ser, Strain C = gal, Strain D = met, Strain E = adeHrf A t = 0mOrigin t=0Hfr B t = 33m his t = 51m。

NBTI degradation From physical mechanisms to modelling

Introductory Invited PaperNBTI degradation:From physical mechanisms to modellingV.Huarda,*,M.Denaisb,c,C.ParthasarathybaPhilips R&D Crolles,850rue Jean Monnet,38926Crolles,FrancebSTMicroelectronics,Central R&D Labs,850rue Jean Monnet,38926Crolles,France cLaboratoire Mate´riaux et Microe ´lectronique de Provence (L2MP –UMR CNRS 6137)–ISEM,Maison des Technologies,Place Georges Pompidou,83000Toulon,FranceReceived 18January 2005Available online 26April 2005AbstractAn overview of the evolution of transistor parameters under negative bias temperature instability stress conditions commonly observed in p-MOSFETs in recent technologies is presented.The physical mechanisms of the degradation as well as the diﬀerent defects involved have been discussed according to a systematic set of experiments with diﬀerent stress conditions.According to our ﬁndings,a physical model is proposed which could be used to more accurately pre-dict the transistor degradation.Finally,based on our new present understanding,a new characterization methodology is proposed,which would open the way to a more accurate determination of parameter shifts and thus allowing imple-menting the degradation into design rules.Ó2005Elsevier Ltd.All rights reserved.1.IntroductionBias temperature instability (BTI)is a degradation phenomenon occurring mainly in MOS Field Eﬀect Transistors (MOSFETs),known since the late 1960s [1,2].Even though the exact root causes of the degrada-tion are not yet well understood,it is now commonly admitted that under a constant gate voltage and an ele-vated temperature a build up of positive charges occurs either at the interface Si/SiO 2or in the oxide layer lead-ing to the reduction of MOSFET performances.Never-theless,this degradation remained marginal for many years,especially when compared to hot carrier injection(HCI)degradation,thanks to the exclusive use of buried channel devices at this time.As a result of aggressive scaling of MOS transistors,the thickness of the gate oxide layer was decreased down to 1.4nm or even lower.In order to improve the transis-tors performances,nitrogen atoms were introduced into the oxide layer by diﬀerent nitridation processes,but mostly by thermal annealing.This nitridation step is in-tended both to give a better control on the gate leakage current and to avoid the boron atoms,used to dope the polysilicon gate,to ﬂow through the oxide into the sub-strate.Besides,the general trend was that most of the de-vices turned out to be surface-channel devices instead of buried-channel ones in recent technologies to counter the short-channel eﬀects inherent of the downscaling process and to improve the performances.As a conse-quence of both the introduction of the nitridation pro-cess step and the use of surface-channel devices,many0026-2714/$-see front matter Ó2005Elsevier Ltd.All rights reserved.doi:10.1016/j.microrel.2005.02.001*Corresponding author.E-mail address:vincent.huard@ (V.Huard).Microelectronics Reliability 46(2006)1–23researchers ascribed an enhanced BTI-like degradation of p-MOSFETs under negative bias and elevated tem-peratures,the so-called NBTI eﬀect[3–5].This work aims to investigate the evolution of tran-sistor parameters under NBTI stress conditions,leading to a general deﬁnition of the Negative Bias Temperature Instability in p-MOSFETs in recent technologies.Sys-tematic sets of experiments have been performed with diﬀerent stress conditions to identify the physical mech-anisms lying behind the degradation.According to our ﬁndings,the interface traps creation is not the sole source of degradation but a major hole trapping eﬀect also occurs.This trapping behaviour is at the origin of a strong recovery eﬀect which makes an accurate mea-surement of the degradation diﬃcult.We propose a new characterisation methodology which gives a more accurate view of the actual degradation.2.Device fabrication and experimental detailsThe devices used in this study were n-and p-MOS-FETs with dual gate process,i.e.n+and p+polysilicongate,respectively,with pure or nitrided(NO)gate oxide layers.Source and drain junctions were formed with ar-senic/phosphorous ion implantations for n-MOSFET and a boron-based implantation for p-MOSFET.Exper-iments were carried out on MOSFETs with oxide thick-ness ranging from 1.6nm to10nm.The MOSFETs have gate lengths ranging from0.1l m to10l m and typ-ically a width of10l m.NBTI stress was applied with the gate electrode held at a low constant negative bias(rang-ing fromÀ0.75V toÀ3.5V)under a temperature ranging from25°C to200°C while the source/drain and n-well electrodes were grounded.In order to characterize the NBTI eﬀect,we primarily used a conventional methodol-ogy based on periodic stops during the stress to measure MOS parameters and/or the two-level charge pumping (CP)current as a measure of the interface traps density. The CP curves are measured with a frequency of105Hz and low gate bias V gl ranging fromÀ0.7V to0.3V and a voltage swing from1V to1.5V.A new characterization methodology will be introduced later in the paper,as it is based on recentﬁndings.Most of the experiments were carried out at125°C unless it is mentioned diﬀerently.2.1.Bias temperature instabilities2.1.1.Degradation of electrical parametersBy deﬁnition,bias temperature instabilities are ob-served when either a capacitor or a transistor is stressed at relatively high temperatures(typically ranging from 80°C to150°C)under a low and constant gate voltage while the source/drain and well electrodes are grounded. The symmetry of stress conditions along the channel proves that this degradation is not related to channel carrier transport.Fig.1shows the typical evolution of I dÀV g curves in linear regime for a p-MOSFET once degraded under NBTI stress conditions for10,000s. Generally,it is observed that after an NBTI stress,the saturated drain current value(I dsat)is reduced.The for-ward and reverse values of the saturated drain current both degrade identically,demonstrating the symmetry of the stress.By the same time,the threshold voltage (V th)is increased as well as the S/D series resistance.Fi-nally,the mobility,as described through the g mÀV g curve is also reduced(cf.Fig.1).Altogether,the degra-dation of these parameters demonstrates the build-up of positive charges close or at the interface of Si/SiO2and yields to a lower level of performance for the transistor. For short stress times,the oﬀ-leakage current is decreas-ing due to the shift of the I dÀV g curves linked to the threshold voltage shift.Nevertheless,in some cases,an increase of the GIDL observed at lowﬁelds may over-come this decrease and limit the performances of the cir-cuit by an increased consumption.The instabilities exist in most of the conﬁgurations, for either p-MOSFETs or n-MOSFETs,and whatever a negative bias and/or a positive bias is applied,except for the n-MOSFET under positive bias,which does ex-hibit almost no degradation.Nevertheless,as shown in Fig.2,applying NBTI stress conditions(i.e.negative gate voltage)on p-MOSFETs represents the most degrading case.That is why the rest of this paper will mainly focus on the mechanisms of p-MOSFET degra-dation under NBTI conditions,but all the conclusions would also apply to the other conﬁgurations.2V.Huard et al./Microelectronics Reliability46(2006)1–232.2.Interface traps creation under NBTI stress conditionsSo far,the microscopic details of the NBTI degrada-tion are not clearly understood but there is a general agreement to say that there is generation of traps at the Si–SiO2interface during negative BT aging.2.3.Nature of interface trapsDue to the lattice mismatch between the bulk silicon and the silicon dioxide and considering the amorphous nature of the dielectrics,some Si atoms at the interface are left unbound when the great majority is bound to oxygen atoms(or nitrogen atoms for the case of nitrided oxides).This trivalent Si atom at the Si/SiO2interface has an unpaired valence electron in a dangling orbital (dangling bond),and is often called Pb centers[6].On (100)-oriented wafers,commonly used for ICs,two de-fects named Pb0and Pb1have been detected by electron spin resonance(ESR)methods,and showed to result from strain relaxation at the interface.These two types of defects have slightly diﬀerent local atomic conﬁgura-tions and so are expected to have slightly diﬀerent elec-trical behaviours.In both cases,these defects have an amphoteric nature.This means that the dangling orbital can be occupied by zero,one or two electrons,which would make the same defect positively charged(donor-like),neutral or negatively charged(acceptor-like), depending on the Fermi level at the interface[7,8].Dur-ing the consecutive process steps,these dangling bonds are generally annealed by hydrogen atoms,which create SiH bonds at the interface.Though considerably improving the initial parameters of the transistor,these bonds might be broken during the operating lifetime of the device,which in turn will lead to a degradation of its parameters.2.4.Role of charge transportIn most of wearout mechanisms,such as hot-carrier injection,oxide breakdown or electromigration,experi-ments pointed out that the charge transport activated directly or indirectly the degradation.Naturally, whether or not the charge transport is related to the NBTI degradation is a question,which has to be an-swered.It should be pointed out that the symmetrical nature of the stress with no drain-to-source potential drop implies that there is no charge transport along the channel.The only remaining displacement of chan-nel carriers is based on their thermal activity.Concern-ing the role of carriersﬂowing through the oxide layer by either direct tunnelling and/or Fowler–Nordheim mechanism,it is interesting to compare both ultra-thin oxides(about2nm-thick)and thicker oxides(about 6.5nm-thick)degradations.In the latter case,the NBTI degradation can be important for these oxides when stressed with a low oxideﬁeld below the detection limit of Fowler–Nordheim current(cf.Fig.3).In that case, the tunnelling probability of carriers through the oxide layer is close to zero which is not the case for thinner oxides under similar oxideﬁeld.Nevertheless,the NBTI degradation monitored in this case is rather similar in spite of the diﬀerent conduction probabilities through the oxide layer.In agreement with many researchers, we have to conclude that the NBTI degradation isV.Huard et al./Microelectronics Reliability46(2006)1–233closely related to the presence of‘‘cold channel holes’’. This assumption is also supported by the small level of degradation for an n-MOSFET under PBTI conditions (cf.Fig.2),where only negligible hole densities can be found on both sides of the oxide layer.Nevertheless, the exact mechanism of degradation involving cold holes remains unknown at this point.2.5.Inﬂuence of channel hole populationIf the channel cold holes are responsible for the NBTI degradation,theﬁrst thing to check out is the ef-fect of varying the hole population by keeping the other stress conditions constant.This conﬁguration can be ob-tained experimentally by two diﬀerent ways.Theﬁrst one is to increase the initial threshold voltage V th0by adding an additional implant.For a similar gate voltage value V g,the oxideﬁeld value would be similar(due to the channel potential grounded to zero)but the channel hole population(proportional to V gÀV th)would de-crease when the threshold voltage is increased.Another way is to change the initial threshold voltage value V th0 by applying a positive bulk bias.In this case,for an increasing positive bulk bias,the threshold voltage value is increased and so that the channel hole population is decreased.Fig.4shows that though V gÀV th is varying by about10%,no changes can be observed in the inter-face traps creation dynamics.In the latter case,some precautions are taken in order to avoid additional degra-dation due to hot holes injection resulting from impact ionisation phenomenon induced by electronsﬂowing through the oxide layer.Basically,for gate voltage up to2.5V,hot electrons coming from the gate demon-strated no impact on electrical parameters.Under hot carrier stress conﬁguration,degradation rates have been found similar whatever the presence of electronsﬂowing through the gate.Fig.4shows that,over a relatively large range of channel hole population(large gate volt-ages range for varying bulk voltages),the electrical parameters shifts are similar and not impacted by vary-ing the hole population(i.e.the bulk voltage).As a con-clusion,if the channel holes are responsible for the observed degradation,their population is not a limiting factor.Ourﬁndings are in agreement with conclusionsof Mitani et al.[9].2.6.Gate voltage or oxideﬁeld dependenceSymmetrically,for diﬀerent bulk biases,the gate volt-age V g is changed in a way to keep V gÀV th constant and so that the channel hole population is made similar. In this case,only the oxideﬁeld is modiﬁed.When the oxideﬁeld is increased,the electrical parameters show a clear increase of their degradation(cf.Fig.5).These results demonstrate the importance of the oxideﬁeld and/or the gate voltage in the degradation.The question of whether the oxideﬁeld or the gate voltage is the driving factor of the degradation remains. Typically,gate voltage dependence is linked to a carrier-energy driven degradation similarly to the case of the gate oxide breakdown and the Channel Hot Carrier (CHC)-induced degradation[10,11].But,as discussed in Fig.3,NBTI degradation occurs also for thick oxides for oxideﬁelds where the gate leakage current is below the detection limit.Therefore,it is diﬃcult to assign the NBTI degradation to energetic carriersﬂowing through the oxide,either holes or electrons,such as pro-posed in[12].In order to investigate the oxideﬁeld4V.Huard et al./Microelectronics Reliability46(2006)1–23dependence,the interface traps creation under NBTI degradation is investigated for diﬀerent gate oxide thick-nesses,ranging from2.1nm to10nm-thick,considering both pure oxides and nitrided oxides with various nitrid-ation processes.Fig.6a shows that for pure oxides stressed with a similar gate voltage the interface traps creation is reduced when the oxide thickness is in-creased.Summarizing a set of pure oxides with four dif-ferent thicknesses stressed with various gate voltages for three diﬀerent stress times,Fig.6b shows that for a given stress time the number of interface traps created are identical for similar oxideﬁelds.These results clearly demonstrate that the oxideﬁeld is the driving force of the interface traps creation during NBTI degradation for pure oxides[13,14].It is questionable if the incorporation of nitrogen atoms into the oxide network will modify this oxide-ﬁeld dependence.As already discussed previously in the introduction,incorporation of nitrogen is known to en-hance the NBTI degradation.Following the approach that NBTI degradation is solely linked to the creation of interface traps,it means that the nitrogen atoms should modify the properties of the interface.Several possibilities have been already discussed in literature as the introduction of mechanical stresses in the atomic structure close to the SiO2/Si interface,a catalytic role [15],an increase of Pb1proportion with respect to the Pb0center[16],a reduction of the activation energy of SiH bond[17].Whatever the mechanism which might be involved here,the incorporation of nitrogen atoms should modify the interface degradation rate.To solveout that question,both n-MOSFETs and p-MOSFETS devices with either pure or nitrided oxides have been stressed under NBTI stress conditions with thicknesses ranging from 2nm to 10nm.Fig.7shows that the inter-face traps creation is identical for pure and nitrided oxi-des over a wide range of oxide thicknesses.It means that for interface traps creation the oxide ﬁeld is the major driving force and not the nature of the oxide itself.A crucial point is raised here because the strong impact of the incorporation of nitrogen on the NBTI degrada-tion is well documented in the literature.But,the inter-face traps creation is not modiﬁed by the presence of nitrogen atoms.This contradiction shows that the inter-face traps cannot be the sole root cause of the device parameter shifts.This point will be discussed further in this paper.2.7.Temperature dependenceBesides the importance of the oxide ﬁeld,the NBTI degradation is also activated with temperature.Fig.8shows the inﬂuence of the temperature on the interface traps creation for temperatures ranging from 50°C to 200°C under similar oxide ﬁeld.The time dynamics present two main characteristics:power law behaviour at low stress times and saturation phenomenon for long stress times.Besides it should be noticed that for low stress times,the power law exponent increases with tem-perature.Fig.9shows that it increases linearly with tem-perature.The combination of these two factors implies that the apparent activation energy E a (as determined through degradation levels in an Arrhenius plot)at a given time is not a constant value.Fig.10shows that E a varies with the stress time,increasing for low stress times and ﬁnally decreasing for long stress times.As a consequence,the interface traps creation is a non-Arrhenius phenomenon [18],which requires a deeper analysis to understand both the temperature dependence and at the end the physical mechanisms lying behind.This analysis is required in order to be able to determine realistic extrapolation laws for various temperatures.2.8.Time dynamicsUnderstanding the physics that lies behind the NBTI degradation requires to understand not only the oxide ﬁeld and temperature dependences of the interface traps creation but also the time dynamics.It is also a strong requirement in order to develop an accurateextrapola-6V.Huard et al./Microelectronics Reliability 46(2006)1–23tion model for device lifetime.A characteristic feature of the interface traps creation during NBTI degradation is its fractional power law time dependence(cf.Fig.11). As most of the published data,our experiments span a range from0.2to0.3for the power law exponent.Nev-ertheless,the fractional time dependence of NBTI degra-dation decreases at longer stress times and indicates a tendency towards saturation.Several phenomenological models have been pro-posed to explain the formation of interface traps associ-ated with NBTI degradation.Jeppson et al.[19] proposedﬁrst a diﬀusion-controlled mechanism to ex-plain the observed time dependence of interface trap generation.Other authors suggested a similar mecha-nism and examined the time dependence of diﬀerent charged diﬀusing species[4,20].Their common assump-tion is that as reaction-limited time dependence obeys a linear relationship,the observed fractional time depen-dence has toﬁnd its origin in a diﬀusion-limited mode. Diﬀusion of hydrogenated species away from the inter-face could possibly explain the power law dependence (t a)of the interface traps creation down to t1/2[4],and indeed,at the time,observed values of power law expo-nents ranged between0.75and0.5.However,in more re-cent years,time-dependencies below t1/2and saturation eﬀects are common for sub-micron devices.Recent stud-ies proposed new evolutions of such approach to explain power law exponents ranging about0.25[21,22].In light of the analysis of such Reaction–Diﬀusion(RD)models, it is possible to distinctly observeﬁve diﬀerent regimes of evolution(cf.Fig.12from[21]).At short times(t<s reac) (regime1),the system is reaction limited with a charac-teristic slope of1,linked directly to the dissociation en-ergy of SiH bonds.In this approach,it is important to notice that all bonds are identical and the system can be described by a single dissociation energy E d.In re-gime2,the reaction is in equilibrium but theﬂux of hydrogen away from the interface is negligible.Regime 3is characterized by the hydrogen diﬀusion limited time dependence described by a power law exponent,which is independent of the oxideﬁeld and/or the temperature but is only determined by the nature of the diﬀusing hydrogenated species.In regime4,the power law expo-nent increases up to0.5due to hydrogen diﬀusion into the gate which is supposed to occur with inﬁnite diﬀu-sion velocity.Finally,in regime5,the generationslowsdown due to saturation of the process and the lack of new bonds to be broken.In order to check the validity of this approach to de-scribe the NBTI degradation,it is important to get some new insights into the interface traps creation during NBTI degradation.One way is to apply preliminary stresses(pre-stress)on the devices in order to break some SiH bonds present at the interface previous to the stress.By doing so,according to the RD model, the regime1should not be impacted since its slope and time constant are only deﬁned by the dissociation energy E d of the bonds.But,a parallel shift downwards of the regime3power law part is expected due to the reduction of the maximum saturation level linked to the maximum number of SiH bonds present previously to the stress.Actually,Fig.13shows that pre-stressing a transistor modiﬁes the reaction-limited part,with a decreasing linear slope(i.e.increasing associated dissoci-ation energy E d)when pre-stress lasts longer.It strictly means that SiH bonds can have various dissociation energies.Concerning the interface traps generation, many authors[23,24]have already reported that the de-fect activation energy of SiH bonds at the interface show a broadened Fermi derivative distribution g(E,r)(with r about0.1eV).In case of distributed dissociation ener-gies,for a given pre-stress time,the slope of the linear part is proportional to the number of SiH bonds for that particular dissociation energy over the characteristic time constant related to this dissociation energy.Our analysis led for two oxideﬁelds on large number of pre-stress times shows that the dissociation energies can beﬁtted by a broadened Fermi derivative distribu-tions with a spread r about0.1eV(cf.Fig.14),as found by other experimental approaches[23,24].In conclusion, we have presented in this section experimental proofs that the SiH bonds at the interface have dispersed disso-ciation energies according to a broadened Fermi deriva-tive distribution.This is an important statement,which will be driven the way we understand and model the interface traps creation.2.9.Model for interface traps creationBreaking a Si–H bond at the interface is often de-scribed by aﬁrst-order reaction such asRðt;sÞ¼1ÀeÀt sÀÁð1Þwhere s represents the time constant of the reaction and is supposed to be directly related to the dissociation en-ergy of the bond E d.Dissociation energy is deﬁned in8V.Huard et al./Microelectronics Reliability46(2006)1–23this case either as the energy to break the SiH bond or the migration barrier the H atoms have to pass over to be released.For degradation times shorter than the time constant(t<s),the degradation rate presents a linear behaviour with time and so a constant defect generation rate P gen=1/s.As shown previously,SiH bonds at the interface do not present a single dissociation energy E d but a contin-uum of energies which,in agreement with other authors [23,24],will be further described by a broadened Fermi derivative distribution g(E d,r)due to disorder-induced variationsgðE d;rÞ¼1re E dmÀE drÀÁ1þe E dmÀE drÀÁ2ð2Þwhere E dm is the median dissociation energy and r is the spread of the distribution with experimental values about0.1eV.In this approach,every single bond is broken accord-ing to aﬁrst-order equation,but each of them with a speciﬁc time constant depending on their own dissocia-tion energy.In consequence,given a range of bond ener-gies,lower-energy bonds would be broken relatively quickly leaving higher-energy bonds to be broken more slowly.The degradation rate results from the combina-tion of every single defectﬁrst-order equation rate, which has been analytically derived as[25]D N it it max ðtÞ¼Z1gðE d;rÞRðt;sðE dÞÞd E d/11þtsÀÁÀað3Þassuming s¼s0expðE dðE oxÞÞand a¼kT for s min<t<s,T being the bond temperature and s min the time constant of the weakest defect.The resulting evolution of the interface traps genera-tion with stress time according to Eq.(3)is shown in Fig.15.For very short times(t<s min),the degradation is lin-ear,with a slope linked to the defect generation rate of the weakest bonds.For longer stress times,more and more diﬀerent bonds participate to the degradation, yielding to power-law dependence such as described in Eq.(3)with aﬁnal saturation when less and less bonds are left to be broken.Fig.16shows that experimentaldynamics for various temperatures can be well repro-duced by Eq.(3),even the saturation eﬀect that is clearly visible at higher temperatures.An important point in describing the temperature behaviour of the interface traps creation is the capability of the model to predict the temperature dependence of the power law exponent.The linear temperature depen-dence of the power law exponent was already pointed out above in Fig.9.In Fig.17,according to Eq.(3), the spread of the distribution r is determined byﬁtting experimental power law exponentsÕevolution and is found to be about0.1eV,as previously deduced by non-related methodologies.Due to the various temperature measurements,not only the spread of the distribution is known but it is also possible to have a close idea of what is the saturation value N it max.For a given value of oxideﬁeld and various temperatures,studying the evolution of the time con-stant s,it is possible to extract the constant s o for 2.1nm nitrided oxide.Its value was found to be 1.34·10À8s in this case(cf.Fig.18).This value was found to be identical for various oxideﬁelds.Once thisV.Huard et al./Microelectronics Reliability46(2006)1–239constant is known,it is possible to study the variation of s with oxideﬁeld.This study yields to the determination of the mean dissociation energy E dm,function of theoxideﬁeld.Fig.19shows that the dissociation energy evolves almost linearly with the oxideﬁeld with aﬂat band limit of about1.5eV,which spans in the range of theoretical values(1.5-1.8eV)proposed by Pantelides et al.[26]for the migration barrier;depending if the hydrogen species migrate away in the substrate or in the oxide.Fig.20shows that using this model allows a good evaluation of the evolution of the apparent activation energy of the interface traps creation.It has to be noted here that if the overall interface traps creation phenom-enon seems to have a non-Arrhenius behaviour,every single bonds considering its own dissociation energy follow an arrhenius behaviour.The deviation from the10V.Huard et al./Microelectronics Reliability46(2006)1–23Arrhenius behaviour only occurs through the existence of the distribution of dissociation energies of the SiH bonds.Besides,this set of parameters allows reproducing not only ultra-thin oxides but also thicker oxides as shown in Fig.21(Nit creation for pure thick oxides with various oxideﬁelds).In conclusion,we have developed a consistent physi-cal-based model of the interface traps creation,which al-lows reproducing all features including oxideﬁeld and temperature dependence over a large range of oxide thickness.3.Threshold voltage degradationSo far,we have made the assumption that the NBTI degradation is only related to the creation of interface traps.We have carefully studied how they are created and how it is inﬂuenced by the various stress parameters. But,to understand the impact of the NBTI degradation up to circuit level,it is important to make the link with device parameters such as threshold voltage.As NBTI degradation is mainly a build-up of charges at the inter-face in a symmetrical conﬁguration along the channel, the threshold voltage parameter is more relevant to de-scribe the degradation than other parameters such as the saturated drain current.3.1.Methodology of measurementsFor the NBTI stress characterization,the devices are typically stressed under a constant gate voltage,gener-ally higher than V dd in order to beneﬁt from an acceler-ated degradation,while the source,drain and bulk are grounded.But the stress is periodically interrupted on a linear or a logarithmic time scale,and device parame-ters(threshold voltage,drive current,etc.)are measured at nominal voltage to monitor the degradation.This ap-proach is based on the assumption that the degradation is permanently generated and cannot be removed once the stress is switched oﬀ.But,as already shown by Ershov et al[27],inserting a delay between stress inter-ruption and measurements yields to a recovery of at least a part of the degradation.Similar experiments were led measuring both the threshold voltage and the inter-face traps creation through CP measurement.As shown in Fig.22,artiﬁcially increased delay between stress interruption and measurements yields also in our case to a partial recovery of the threshold voltage shift.But it is important to notice that the number of interface traps created during the stress is similar.By the way,it is important here to consider the number of interface traps as determined through the integration of the bell-like CP curve and not to make a direct link with the maximum value of the CP current I cpmax.Actually,dur-ing the recovery phase,I cpmax is slightly reduced but the width of the bell-like CP curve is also changed.Leading the integration of this curve shows that the total number of interface traps created during the stress remains con-stant in spite of the reduction of I cpmax.The combination of the unchanged interface traps density,the partial recovery of threshold voltage and the modiﬁed edges of the bell-like CP curve with an increased delay points out the fact that the NBTI-induced threshold voltage degradation is not only related to the creation of inter-face traps but a second component has to be taken intoaccount.。

inTroDUCTion：我roducNTT离子

i n T r o D U C T i o nString theory is a mystery. it’s supposed to be the the-ory of everything. But it hasn’t been verified experimen-tally. And it’s so esoteric. it’s all about extra dimensions, quantum fluctuations, and black holes. how can that be the world? Why can’t everything be simpler?String theory is a mystery. its practitioners (of which i am one) admit they don’t understand the theory. But calculation after calculation yields unexpectedly beautiful, connected results. one gets a sense of inevitability from studying string theory. how can this not be the world? how can such deep truths fail to connect to reality?String theory is a mystery. it draws many talented gradu-ate students away from other fascinating topics, like super-conductivity, that already have industrial applications. it attracts media attention like few other fields in science. And it has vociferous detractors who deplore the spread of its influence and dismiss its achievements as unrelated to em-pirical science.Briefly, the claim of string theory is that the fundamental objects that make up all matter are not particles, but strings. Strings are like little rubber bands, but very thin and very strong. An electron is supposed to be actually a string, vibrat-ing and rotating on a length scale too small for us to probe even with the most advanced particle accelerators to date. in2some versions of string theory, an electron is a closed loop of string. in others, it is a segment of string, with two endpoints. Let’s take a brief tour of the historical development of string theory.String theory is sometimes described as a theory that was invented backwards. Backwards means that people had pieces of it quite well worked out without understanding the deep meaning of their results. first, in 1968, came a beautiful for-mula describing how strings bounce off one another. The formula was proposed before anyone realized that strings had anything to do with it. Math is funny that way. formulas can sometimes be manipulated, checked, and extended without being deeply understood. Deep understanding did follow in this case, though, including the insight that string theory in-cluded gravity as described by the theory of general relativity. in the 1970s and early ’80s, string theory teetered on the brink of oblivion. it didn’t seem to work for its original pur-pose, which was the description of nuclear forces. While it incorporated quantum mechanics, it seemed likely to have a subtle inconsistency called an anomaly. An example of an anomaly is that if there were particles similar to neutrinos, but electrically charged, then certain types of gravitational fields could spontaneously create electric charge. That’s bad because quantum mechanics needs the universe to maintain a strict balance between negative charges, like electrons, and positive charges, like protons. So it was a big relief when, in 1984, it was shown that string theory was free of anomalies. it was then perceived as a viable candidate to describe the universe. This apparently technical result started the “first super-string revolution”: a period of frantic activity and dramatic advances, which nevertheless fell short of its stated goal, to produce a theory of everything. i was a kid when it got going,i n T r o D U C T i o n3 and i lived close to the Aspen Center for Physics, a hotbed of activity. i remember people muttering about whether super-string theory might be tested at the Superconducting Super Collider, and i wondered what was so super about it all. Well, superstrings are strings with the special property of supersym-metry. And what might supersymmetry be? i’ll try to tell you more clearly later in this book, but for now, let’s settle for two very partial statements. first: Supersymmetry relates particles with different spins. The spin of a particle is like the spin of a top, but unlike a top, a particle can never stop spinning. Sec-ond: Supersymmetric string theories are the string theories that we understand the best. Whereas non-supersymmetric string theories require 26 dimensions, supersymmetric ones only require ten. naturally, one has to admit that even ten dimensions is six too many, because we perceive only three of space and one of time. Part of making string theory into a theory of the real world is somehow getting rid of those extra dimensions, or finding some useful role for them.for the rest of the 1980s, string theorists raced furiously to uncover the theory of everything. But they didn’t under-stand enough about string theory. it turns out that strings are not the whole story. The theory also requires the existence of branes: objects that extend in several dimensions. The sim-plest brane is a membrane. Like the surface of a drum, a membrane extends in two spatial dimensions. it is a surface that can vibrate. There are also 3-branes, which can fill the three dimensions of space that we experience and vibrate in the additional dimensions that string theory requires. There can also be 4-branes, 5-branes, and so on up to 9-branes. All of this starts to sound like a lot to swallow, but there are solid reasons to believe that you can’t make sense of string theory without all these branes included. Some of these reasons havei n T r o D U C T i o n4to do with “string dualities.” A duality is a relation between two apparently different objects, or two apparently differ-ent viewpoints. A simplistic example is a checkerboard. one view is that it’s a red board with black squares. Another view is that it’s a black board with red squares. Both viewpoints (made suitably precise) provide an adequate description of what a checkerboard looks like. They’re different, but related under the interchange of red and black.The middle 1990s saw a second superstring revolution, based on the emerging understanding of string dualities and the role of branes. Again, efforts were made to parlay this new understanding into a theoretical framework that would qualify as a theory of everything. “everything” here means all the aspects of fundamental physics we understand and have tested. gravity is part of fundamental physics. So are electromagnetism and nuclear forces. So are the particles, like electrons, protons, and neutrons, from which all atoms are made. While string theory constructions are known that reproduce the broad outlines of what we know, there are some persistent difficulties in arriving at a fully viable theory. At the same time, the more we learn about string theory, the more we realize we don’t know. So it seems like a third superstring revolution is needed. But there hasn’t been one yet. instead, what is happening is that string theorists are trying to make do with their existing level of understanding to make partial statements about what string theory might say about experiments both current and imminent. The most vigorous efforts along these lines aim to connect string theory with high-energy collisions of protons or heavy ions. The connections we hope for will probably hinge on the ideas of supersymmetry, or extra dimensions, or black hole horizons, or maybe all three at once.i n T r o D U C T i o n5 now that we’re up to the modern day, let’s detour to con-sider the two types of collisions i just mentioned.Proton collisions will soon be the main focus of experi-mental high-energy physics, thanks to a big experimental fa-cility near geneva called the Large hadron Collider (LhC). The LhC will accelerate protons in counter-rotating beams and slam them together in head-on collisions near the speed of light. This type of collision is chaotic and uncontrolled. What experimentalists will look for is the rare event where a collision produces an extremely massive, unstable particle. one such particle—still hypothetical—is called the higgs boson, and it is believed to be responsible for the mass of the electron. Supersymmetry predicts many other particles, and if they are discovered, it would be clear evidence that string theory is on the right track. There is also a remote possi-bility that proton-proton collisions will produce tiny black holes whose subsequent decay could be observed.in heavy ion collisions, a gold or lead atom is stripped of all its electrons and whirled around the same machine that carries out proton-proton collisions. When heavy ions collide head-on, it is even more chaotic than a proton-proton collision. it’s believed that protons and neutrons melt into their constituent quarks and gluons. The quarks and gluons then form a fluid, which expands, cools, and eventually freezes back into the particles that are then observed by the detectors. This fluid is called the quark-gluon plasma. The connection with string theory hinges on comparing the quark-gluon plasma to a black hole. Strangely, the kind of black hole that could be dual to the quark-gluon plasma is not in the four dimensions of our every-day experience, but in a five-dimensional curved spacetime. it should be emphasized that string theory’s connections to the real world are speculative. Supersymmetry might simplyi n T r o D U C T i o n6not be there. The quark-gluon plasma produced at the LhC may really not behave much like a five-dimensional black hole. What is exciting is that string theorists are placing their bets, along with theorists of other stripes, and holding their breaths for experimental discoveries that may vindicate or shatter their hopes.This book builds up to some of the core ideas of modern string theory, including further discussion of its potential applications to collider physics. String theory rests on two foundations: quantum mechanics and the theory of relativ-ity. from those foundations it reaches out in a multitude of directions, and it’s hard to do justice to even a small fraction of them. The topics discussed in this book represent a slice across string theory that largely avoids its more mathemati-cal side. The choice of topics also reflects my preferences and prejudices, and probably even the limits of my understand-ing of the subject.Another choice i’ve made in writing this book is to dis-cuss physics but not physicists. That is, i’m going to do my best to tell you what string theory is about, but i’m not going to tell you about the people who figured it all out (although i will say up front that mostly it wasn’t me). To illustrate the difficulties of doing a proper job of attributing ideas to people, let’s start by asking who figured out relativity. it was Albert einstein, right? yes—but if we just stop with that one name, we’re missing a lot. hendrik Lorentz and henri Poincaré did important work that predated einstein; her-mann Minkowski introduced a crucially important math-ematical framework; David hilbert independently figured out a key building block of general relativity; and there are several more important early figures like James Clerk Max-well, george fitzgerald, and Joseph Larmor who deservei n T r o D U C T i o n7 mention, as well as later pioneers like John Wheeler and Subrahmanyan Chandrasekhar. The development of quan-tum mechanics is considerably more intricate, as there is no single figure like einstein whose contributions tower above all others. rather, there is a fascinating and heterogeneous group, including Max Planck, einstein, ernest rutherford, niels Bohr, Louis de Broglie, Werner heisenberg, erwin Schrödinger, Paul Dirac, Wolfgang Pauli, Pascual Jordan, and John von neumann, who contributed in essential ways—and sometimes famously disagreed with one another. it would be an even more ambitious project to properly as-sign credit for the vast swath of ideas that is string theory. My feeling is that an attempt to do so would actually de-tract from my primary aim, which is to convey the ideas themselves.The aim of the first three chapters of this book is to in-troduce ideas that are crucial to the understanding of string theory, but that are not properly part of it. These ideas— energy, quantum mechanics, and general relativity—are more important (so far) than string theory itself, because we know that they describe the real world. Chapter 4, where i introduce string theory, is thus a step into the unknown. While i attempt in chapters 4, 5, and 6 to make string the-ory, D-branes, and string dualities seem as reasonable and well motivated as i can, the fact remains that they are un-verified as descriptions of the real world. Chapters 7 and 8 are devoted to modern attempts to relate string theory to experiments involving high-energy particle collisions. Supersymmetry, string dualities, and black holes in a fifth dimension all figure in string theorists’ attempts to under-stand what is happening, and what will happen, in particle accelerators.i n T r o D U C T i o n8In various places in this book, I quote numerical values for physical quantities: things like the energy released in nuclear fission or the amount of time dilation experienced by an Olympic sprinter. Part of why I do this is that physics is a quantitative science, where the numerical sizes of things matter. However, to a physicist, what’s usually most interesting is the approximate size, or order of magnitude, of a physical quantity. So, for example, I remark that the time dilation experienced by an Olympic sprinter is about a part in 1015 even though a more precise estimate, based on a speed of 10 m/s, is a part in 1.8 × 1015. Readers wishing to see more precise, explicit, and/or extended versions of the calculations I describe in the book can visit this website: /titles/9133.html.Where is string theory going? String theory promises to unify gravity and quantum mechanics. It promises to provide a single theory encompassing all the forces of nature. It promises a new understanding of time, space, and additional dimensions as yet undiscovered. It promises to relate ideas as seemingly distant as black holes and the quarkgluon plasma. Truly it is a “promising” theory!How can string theorists ever deliver on the promise of their field? The fact is, much has been delivered. String theory does provide an elegant chain of reasoning starting with quantum mechanics and ending with general relativity. I’ll describe the framework of this reasoning in chapter 4. String theory does provide a provisional picture of how to describe all the forces of nature. I’ll outline this picture in chapter 7 and tell you some of the difficulties with making it more precise. And as I’ll explain in chapter 8, string theory calculations are already being compared to data from heavy ion collisions.I N TR O D U C TI O N9i don’t aim to settle any debates about string theory in this book, but i’ll go so far as to say that i think a lot of the disagreement is about points of view. When a noteworthy result comes out of string theory, a proponent of the theory might say, “That was fantastic! But it would be so much bet-ter if only we could do thus-and-such.” At the same time, a critic might say, “That was pathetic! if only they had done thus-and-such, i might be impressed.” in the end, the pro-ponents and the critics (at least, the more serious and in-formed members of each camp) are not that far apart on matters of substance. everyone agrees that there are some deep mysteries in fundamental physics. nearly everyone agrees that string theorists have mounted serious attempts to solve them. And surely it can be agreed that much of string theory’s promise has yet to be delivered upon.i n T r o D U C T i o n。

b823236a

Experimental evidence for interactions between anions and electron-deﬁcient aromatic ringsOrion B.Berryman ab and Darren W.Johnson*abReceived (in Austin,TX,USA)5th January 2009,Accepted 2nd February 2009First published as an Advance Article on the web 9th April 2009DOI:10.1039/b823236aThis feature article summarizes our research aimed at using electron-deﬁcient aromatic rings to bind anions in the context of complementary research in this active ﬁeld.Particular attention is paid to the diﬀerent types of interactions exhibited between anions and electron-deﬁcient arenes in solution.The 120+references cited in this article underscore the ﬂurry of recent activity by numerous researchers in this ﬁeld,which was relatively nascent when our eﬀorts began in 2005.While the interaction of anions with electron-deﬁcient aromatic rings has recently garnered much attention by supramolecular chemists,the observation of these interactions is not a recent discovery.Therefore,we begin with a historical perspective on early examples of anions interacting with electron-deﬁcient arenes.An introduction to recent (and not so recent)computational investigations concerning anions and electron-deﬁcient aromatic rings as well as a brief structural survey of crystallineexamples of this interaction are provided.Finally,the limited solution-based observations of anions interacting with electron-deﬁcient aromatic rings are summarized to introduce our currentinvestigations in this area.We highlight three diﬀerent systems from our lab where anion–arene interactions have been investigated.First,we show that tandem hydrogen bonds and anion–arene interactions augment halide binding in solution.Second,a crystallographic and computational study highlights the multiple types of interactions possible between anions and electron-deﬁcient arenes.Third,we summarize the ﬁrst example of a class of designed receptors that emphasize the diﬀerent types of anion–arene interactions possible in solution.1.IntroductionThis article highlights our progress towards designing receptors that bind anions in solution using electron-deﬁcient arenes inthe context of the current state-of-the-art in the ﬁeld.Parti-cular emphasis is placed on reviewing examples of these interactions in solution from other researchers and summarizing our complementary studies.Due to the burgeoning examples of reversible anion–arene attractions,it is easy to assume that this is a modern discovery.1–4However,it is important not to overlook the origins of attractions between anions and electron-deﬁcient aromatic rings.A recent review by Bryantsev and Hay alsoaDepartment of Chemistry and Materials Science Institute,University of Oregon,Eugene,OR 97403-1253,USA.E-mail:dwj@;Fax:+15413460487;Tel:+15413461695bThe Oregon Nanoscience and Microtechnologies Institute (ONAMI),OR,USA.Web:Orion B.BerrymanOrion B.Berryman was born and raised in Homer,Alaska.While attending college at the University of New Hampshire,Orion earned a minor in music and a BA in Chemistry under the supervision of Glen ler.In 2008he received his PhD in Chemistry under the guidance of Darren W.Johnson,where his work focused on studying subtle interactions between anions and electron-deﬁcient aromatic rings.Orion is currently a post-doctoral fellow working for Dr Julius Rebek,Jr.at the Scripps ResearchInstitute.Darren W.JohnsonDarren W.Johnson received his BS in Chemistry at the University of Texas at Austin in 1996,where he performed undergraduate research under the direction of Jonathan L.Sessler.He earned his PhD in Chemistry in 2000from the University of California at Berkeley working with Kenneth N.Raymond,and he then spent two years at the Scripps Research Institute as a National Institutes of Health post-doctoral fellow with Julius Rebek,Jr.He joinedthe chemistry faculty at the University of Oregon as an assistant professor in 2003and is also a member of the UO Materials Science Institute.This journal iscThe Royal Society of Chemistry 2009mun.,2009,3143–3153|3143FEATURE ARTICLE /chemcomm |ChemCommhighlights this perspective.5Initial reports from Jackson et al. in the late1800s of highly colored complexes formed when electron-deﬁcient picryl ethers were mixed with potassium alkoxides6,7eventually led to isolation of the covalent Jackson–Meisenheimer complexes,which are considered to be isolable intermediates on the nucleophilic aromatic substitution pathway (Fig.1).8The isolation and characterization of Jackson–Meisenheimer complexes were initially complicated by a number of both reversible and non-reversible interactions between the anion (a strong nucleophile in this case)and the p-system.The various interaction types are characterized by the degree of participation of the donor(anion)atom’s electron pair.9For instance,p-complexes(also known as donor–acceptor or charge-transfer complexes)can form as a result of partial transfer of electron density from an electron-rich donor(or anion)through the LUMO orbital of an electron-deﬁcient aromatic ring(Fig.2,1).10Additionally,s-complexes(Jackson–Meisenheimer complexes)arise as a result of the donor atom forming a covalent bond with an atom of the electron-deﬁcient aromatic ring(Fig.2,3).Other possible interactions include proton transfer from the electron-deﬁcient aromatic ring to the donor atom(Fig.2,4and5),as well as substitution of aromatic substituents or complete transfer of an electron from the donor to the electron-deﬁcient aromatic ring (Fig.2,2).The subtleties of many of these interactions have been appreciated since the late1960s with a number of reviews devoted to the subject.9,11–16Early examples of anion–arene interactions:computations and mass spectrometryThe assortment of possible anion–arene interactions identiﬁed suggested a dependence on both the nucleophilicity of the anion and the degree of electron-deﬁciency of the aromatic ring.This multitude of binding geometries was later experimentally and theoretically established from electron aﬃnities measured from gas-phase ion-molecule equilibrium measurements with pulsed electron high ion source pressure mass spectrometers17–23 and supporting molecular orbital discussions/calculation.24–28 Interestingly,gas-phase techniques have resurfaced as a popular method to study related anion–arene interactions.29,302.Renaissance of anion–arene interactions Computations:anion–p,weak r and C–HÁÁÁXÀhydrogen bonds The recent publication of higher level computations quantifying the interaction of anions with electron-deﬁcient aromatic rings has spurred interest in the supramolecular chemistry community.31–33As a result,a renaissance in computational studies has emerged looking at a variety of anions.This section serves as an overview on this topic,as relevant computations have been thoroughly reviewed elsewhere.1a,2,4,5 The most computationally studied anions to date are simple monoatomic ions,34–62but recent studies have progressed to more complicated polyatomic anions with an assortment of geometries.31–35,53,63–71As for the electron-deﬁcient aromatic ring,the most popular targets for study have beenﬂuorinated aromatic rings like hexaﬂuorobenzene or heterocyclic rings such as triazine.31–34,36,37,39,41,44–54,56–59,61,62,64,66,68,71However, most of these computations have focused on symmetric non-covalent interactions,coined‘anion–p interactions’(Fig.3,A). Other forms of attractive interactions between anions and electron-deﬁcient aromatic rings have not received such scrutiny despite their emerging relevance in solution-phase studies(see Sections3and4).In fact,the anion–p interaction was promulgated so comprehensively that in our early solution studies we neglected to consider other binding motifs in our receptor design.72Upon further crystallographic and compu-tational study,32,73,74we began to appreciate the rich variety of attractive interactions between anions and electron-deﬁcient aromatic rings.These include a centered electrostatic inter-action(A),an oﬀ-centered weak s interaction(B and C),and when available,aryl C–H hydrogen bonds(D,Fig.3).Aﬂourish of anion–arene crystal structuresThe numerous computational descriptions of anion–arene complexes have coincided with increasing reports of crystal structures illustrating anions positioned appropriately close to electron-deﬁcient aromatic rings.This section brieﬂy high-lights several representative examples of diﬀerent interaction types found in crystal structures,and the references cited provide a more complete list of structural examples.WehaveFig.3MP2/aug-cc-pVDZ optimized geometries for ClÀinteractionswith1,2,4,5-tetracyanobenzene:(A)an unstable anion–p complex,(B and C)weak s complexes,(D)an aryl C–H hydrogen bondcomplex.3144|mun.,2009,3143–3153This journal is c The Royal Society of Chemistry2009omitted examples of aryl C–H hydrogen bonds,as these have been elegantly described in recent publications and reviews.5,75–85In addition to interactions between the anion and an electron-deﬁcient arene,many of these solid state examples also exhibit additional supporting forces.For instance,in many cases the electronics of the aromatic ring is perturbed by direct coordination of a metal cation.35,73,77,86–103In other cases,the anion is present to balance charge or to ﬁll space in porous networks formed from metal organic frameworks.Such interactions have been shown to inﬂuence the solid state morphology of these frameworks.70,104A representative example of a counter anion interacting with metal-coordinated pyridine rings is shown in Fig.4,where a chloride ion is sandwiched between four pyridyl groups coordinated to two diﬀerent copper ions within an octapyridyl ligand.91In the solid state,two of the non-coordinating chloride counterions each exhibit four short contacts with aromatic centroids of adjacent copper-coordinated pyridine moieties.Additional solid state examples of these interactions come from crystal structures where both anion–arene inter-actions and ion pairing are employed to attract anions to a receptor.105–109One illustrative example of tandem ionic hydrogen bond formation and anion–arene interactions is shown in Fig.5,where a cyanuric acid derivative adorned with an ammonium substituent crystallizes with the Cl Àcounter anion over the face of the arene ring (Fig.5).41The other examples from this article show that the anions (Cl À,Br Àand I À)are located slightly oﬀ-center from the aromatic ring centroid and are stabilized by both hydrogen bonds with the positively charged ammonium substituent and contacts with the electron-deﬁcient cyanuric acid derivative.Numerous otherstructural examples augment the interaction of an anion with electron-deﬁcient arenes by stabilizing the complex using,e.g.,hydrogen bonding,and many of these are highlighted in Section 3.50–51,69,110–114Another example of tandem ion pairing and interaction with electron-deﬁcient aromatic rings comes from Mascal and co-workers.56,112A cyanuric acid-based cylindrophane was computationally designed and experimentally synthesized to bind ﬂuoride.The ﬂuoride anion in this structure is contained within this cage structure surrounded by three ammonium substituents around the equator and two electron-deﬁcient rings above and below.The multitude of interactions present in crystal structures makes the exclusive isolation of only anion–arene interactions a challenging endeavor.Examples that utilize only anion–arene interactions to position anions near electron-deﬁcient aromatic rings are quite rare.74,115For example,Kochi and co-workers co-crystallized electron-deﬁcient p -systems with alkyl ammonium Br Àand I Àsalts.The solid state structures of electron-deﬁcient arenes such as tetracyanopyrazine with Br Àreveal multiple close contacts in the solid state depending on the ratio of starting materials (Fig.6).In addition to the recent solid state highlights of anion–arene interactions,Cambridge Structure Database (CSD)searches reveal numerous structures exemplifying anion–arene interactions.In fact,a recent review on the subject even noted that due to the abundance of such contacts in the CSD,‘‘anion–p contacts are ...not particularly exceptional in solid state structures.’’1b The following sections highlight solution evidence for anion–arene interactions,and,when present,complementary crystallographic studies are also described.3.Evidence for anion–arene interactions in solutionEarly evidenceWhile there is a large body of research on strongly covalent anion–arene (Jackson–Meisenheimer)complexes,we were interested in designing anion receptors that incorporate electron-deﬁcient aromatic rings to bind anions reversibly in solution.This section of the review focuses on non-covalent or weakly covalent,reversible anion–areneinteractions.Fig.4Single crystal X-ray structure from Reedijk and co-workers illustrating chloride–pyridine contacts in a copper (II )-coordinated octadentate pyridine ligand.91Hydrogen atoms (left)and additional chloride counter anions have been omitted for clarity.Chlorides are represented as spheres while ligands and metals are represented assticks.Fig.5Single crystal X-ray structure of ethyl ammonium-substituted thiocyanuric acid,illustrating both ionic hydrogen bonding and anion–arene interactions with chloride.41Fig.6A portion of the tetracyanopyrazine–Br Àsingle crystal X-ray structure.Halides exhibit multiple oﬀ-center contacts in the solid state;the number of electron-deﬁcient aromatic rings surrounding the anion is dependent on the starting ratio.74This journal iscThe Royal Society of Chemistry mun.,2009,3143–3153|3145Given the relatively weak nature of anion–arene inter-actions,only a handful of attempts have been made to measure these interactions in solution.Indeed,only two such examples existed at the outset of our research.Furthermore,at that point in time,no designed receptors had been shown to exhibit anion–arene interactions in solution.However,in 1991,Schneider measured associations between sulfonate-substituted aromatic rings and charge neutral aromatic rings in solution.116These insightful measurements likely represent contributions from both p-stacking and anion–arene inter-actions that are occurring in solution and provide an early observation of anion–arene interactions.More recently,Kochi and co-workers utilized UV-Vis spectroscopy to measure association constants between halides and commercially available electron-deﬁcient p-systems.74Association constants of alkyl ammonium salts of BrÀand IÀwith1,2,4,5-tetra-cyanobenzene,1,3,5-trinitrobenzene and tetracyanopyrazine were found to range from0.8to9MÀ1in acetonitrile–dichloromethane solutions.Measuring anion–arene interactions in solution:tandem hydrogen bonds and electron-deﬁcient aromatic ringsOur initial study aimed to design a receptor capable of binding anions in solution utilizing an electron-deﬁcient aromatic ring. Based on the existing computational studies at the time,we felt it was necessary to incorporate an electron-deﬁcient aromatic ring and a complementary hydrogen bond donor into ourﬁrst generation receptor design.This two-point recognition motif was compared to a control receptor lacking the electron-deﬁcient aromatic ring to provide us an estimation of the strength of anion–arene interactions in this system.72 Synthesis and crystal structuresOwing to the synthetic accessibility and abundant computational studies onﬂuorinated aromatics at the time,we chose the electron-deﬁcient pentaﬂuorophenyl substituent as the aromatic binding motif and a sulfonamide proton as the hydrogen bond donor.Receptor5and control receptor6were synthesized as shown in Scheme1.Single crystals suitable for X-ray diﬀraction were obtained illustrating that receptors5and6are preorganized to bind anions in the solid state.117Notably,the sulfonamide proton is positioned directly above the aromatic ring so that receptors5 and6are in an optimal conformation to interact with an anion through both a hydrogen bond and an aromatic ring.Receptor 5crystallizes as a hydrogen bonded dimer with one sulfonamide oxygen positioned directly above the pentaﬂuorophenyl substituent(3.1A)of another molecule(Fig.7,upper left). Receptor6also adopts a dimeric conformation in the solid state(Fig.7,upper right).However,the sulfonamide oxygen is positioned signiﬁcantly farther away from the adjacent aromatic ring(3.6A)suggesting that the electron-rich species (sulfonamide oxygen in this case)is less attracted to the more electron-rich aromatic ring.Solution studiesWith receptors5and6synthesized we turned to1H NMR spectroscopic titrations to measure association constants between each receptor and tetra-n-butyl ammonium halides (ClÀ,BrÀand IÀ).Receptor5exhibited modest binding with ClÀ,BrÀand IÀresulting in average association constants of 34MÀ1,20MÀ1and30MÀ1,respectively.The measured association constants for5were similar in magnitude to the only other previously reported anion–arene binding constants at that time.74,116Interestingly,control receptor6—notably lacking an electron-deﬁcient aromatic ring—exhibited no measureable binding for the halides.By comparing the association constants for the nearly isosteric receptors we arrived at an initial estimation for the strength of anion–arene interactions in solution.This solution data emphasized our suggestion that electron-deﬁcient aromatic rings can be successfully incorporated as a key component to a design strategy to bind anions in solution.CocrystalsCocrystals of receptor5with tetra-n-butyl ammonium halides were sought to illustrate the anion–arene interaction in the solid state.Unfortunately,after Herculean eﬀort to isolate cocrystals of these complexes,the only structure obtained contained receptor5and tetra-n-butyl ammonium bromide (Fig.8).Prominent in this structure is the strong polymericionFig.7Stick(top)and CPK(bottom)representations of receptors5and6in the solid state.72Carbon is colored gray,nitrogen blue,oxygen red,ﬂuorine light blue,sulfur yellow and hydrogen white. 3146|mun.,2009,3143–3153This journal is c The Royal Society of Chemistry2009pair formed between the tetra-n -butyl ammonium counterions and the bromide anions.As a result receptor 5rotates out of conjugation to form a weak hydrogen bond with the bromide anion with a Br–H–N angle of 129.71.This structure does not likely represent what is occurring in solution.First,the polymeric ion pair observed in the solid state is not completely maintained in CDCl 3solutions.Furthermore,this ion pairing in solution would not explain the chemical shift dependence of the N-H resonance of 5on anion concentration.Moreover,the structural similarities between receptors 5and 6would allow them both to adopt the same twisted conformation which would result in similar binding constants for the two receptors,which was not putational studiesComplementary computational studies were also performed which supported our solution studies and contest the observed solid state conformation.In collaboration with Prof.Fraser Hof at the University of Victoria we showed that the chloride anion is repulsed by the aromatic ring in 6while being attracted to the electron-deﬁcient aromatic ring of 5according to Hartree–Fock (6-31+G*)geometry minimizations performed on both Cl Àcomplexes (Fig.9).These studies provided support for anion–arene interactions in solution,and the encouraging preliminary evidence suggested that this inter-action could be used to bind anions by design.Recent examples of anion–arene interactions in solution More recently,elegant receptor molecules illustrate or have been designed to illustrate anion–arene interactions.However,the large number of competing interactions in solution often requires the use of additional attractive forces to measure the relatively weak anion–arene interactions.Hydrogen bonds have been employed in receptors most often to assist in attracting anions to electron-deﬁcient aromatic rings.72,75,107,111,118,119An elegant example of a series of calix[4]pyrrole receptors that contain varying degrees of electron-deﬁcient aromatic rings to assist in halide binding was reported by Ballester and co-workers.118An enhancement of anion binding is observed over a similar control receptor even when only modestly electron-deﬁcient nitrobenzene substituents are attached to the receptor core.A single crystal X-ray structure illustrates the position of the chloride within the receptor’s electron-deﬁcient cavity (Fig.10),and solution studies show that each nitrobenzene functionality provides B 0.1kcal mol À1binding energy in this system.Other supporting attractive interactions that have been employed include ionic hydrogen bonding.For instance,Ghosh and co-workers developed both amine and urea tripodal anion receptors containing pentaﬂuorophenyl arenes attached to a tris(2-aminoethyl)amine scaﬀold.When three of the amines are protonated,the amine receptor binds halides in d 6-DMSO with binding constants for the p -toluene sulfonate derivative ranging from 363to 110M À1for Cl Àand Br À,respectively.The tetraﬂuoroborate derivative exhibited slightly enhanced binding at 479M À1for Cl Àand 141M À1for Br À.The X-ray crystal structure also reveals close anion–arene contacts (Fig.11).107The analogous urea receptor exhibits anion binding in solution with association constants of 3.31Â105M À1measured for H 2PO 4Àand 2.82Â104M À1for CH 3COO À.111The crystal structure reveals that the urea forms a cage around a H 2PO 4Àdimer in the solid state exhibiting multiple hydrogen bonds and contacts with the pentaﬂuorophenyl substituents.Metal coordination has also been employed to assist anion binding in solution.An excellent review based on a keynote lecture addresses some key aspects of this topic.120As one representative example,Holman and Fairchild were the ﬁrsttoFig.8Stick representation of the X-ray crystal structure of 5and tetra-n -butyl ammonium bromide where the ion pairing in the solid state forces the sulfonamide N-H away from the preferred conformation.72The inset shows the polymeric ion pair formed in the solidstate.Fig.9HF (6-31+G*)geometry minimizations of receptors 5and 6.(a)Energy minimization of receptor 5with chloride (green)illustrating the halide over the face of the electron-deﬁcient aromatic ring.(b)One of the representative minimizations of receptor 6with chloride (green)oﬀset from the center of the aromaticring.Fig.10Single crystal X-ray structure of a neutral calix[4]pyrrole anion receptor hydrogen bonding to Cl Àand forming four Cl À–nitrobenzene contacts.118This journal iscThe Royal Society of Chemistry mun.,2009,3143–3153|3147highlight a fully ruthenium metallated cryptophane that binds anions within its cavity.921H and 19F NMR spectroscopy unequivocally showed in solution the encapsulation of anions such as CF 3SO 3À,SbF 6Àand PF 6Àin the metallated molecular container.CF 3SO 3Àor SbF 6Àare also contained within the cavity in the solid state and a representative crystal structure is shown in Fig.12.A recent report by Wang and co-workers presents a macro-cyclic dichloro-substituted tetraoxacalix[2]arene[2]-triazine molecule that forms complexes with F Àand Cl Àin solution and Cl Àand Br Àin the solid state.114In the crystalline assembly two calixarene molecules form ternary complexes with one water and one halide (Cl Àor Br À),suggesting an intricate association of H 2O hydrogen bonding,anion–arene attractions and lone pair–p interactions (Fig.13).Amazingly,association constants for these complexes measure about 4000M À1for F Àand Cl À,orders of magnitude larger than the only other reported association constants for neutral electron-deﬁcient arenes with halides.72,74,116These appealing complexes represent a rare example of neutral electron-deﬁcient arene-bearing receptors interacting with anions.The strong association of Cl Àand F Àin this system certainly warrants further investigation.Supporting solution evidence for anion–arene interactions Recently,a number of reports have surfaced providing evidence for the importance of anion–arene interactions in chemical reactivity and anion transport.In one example,Matile and co-workers have introduced rigid oligo-(p -phenylene)-N ,N -naphthalenediimide rods to transport anions across lipid bilayers.121–123The transport activity of these rods was aﬀected by external anion exchange,but largely unaﬀected by external cation exchange supporting the assertion that anion –arene interactions are operative in this system.122Inter-estingly,selectivity for chloride over other halides is achieved when certain termini are employed.Additionally,rigid anion slides which incorporate electron-deﬁcient naphthalene diimides are capable of demonstrating artiﬁcial photosynthetic activity in their transport of anions and electrons across membranes.123Preference was observed for OH Àover SO 42À,NO 3À,ClO 4Àand Cl À.Other exciting applications of anion–arene interactions involve stabilizing transition states and accelerating reactions.One such observation is exempliﬁed in a series of macro-cyclization reactions en route to the total synthesis of acerogenins A,B,C and L:anion–arene interactions stabilize a bent conformation leading to the product.124,125Anion–arene interactions have also been invoked to explain the rates of free radical halogen-abstraction reactions in a series of anthracene derivatives,1-phenyl-4-bromodecane and a non-aromatic control molecule.126DFT calculations and experimentally measured reaction rates suggest that the presence of an aromatic ring in these systems stabilizes the electron-rich transition state.Nearly an 8-fold increase in reaction rate is observed for a nitro-substituted anthracene derivative over a nearly isostructural methyl derivative.The fact that practical examples of anion–arene interactions are being presented in the literature is an exciting prospect for this ﬁeld of research.As our collective understanding of anion–arene interactions broadens,additional applications of anion–arene interactions will certainlyemerge.Fig.11X-Ray crystal structure of a tripodal receptor–Cl Àcomplex.The receptor binds anions using both ionic hydrogen bonds and electron-deﬁcient aromatic rings.107The tripodal receptor molecule is represented as a wireframe and the Cl Àas asphere.Fig.12Single crystal X-ray structure of a ruthenium permetallatedcryptophane that encapsulates CF 3SO 3Àaided by six anion–arene interactions.Hydrogen atoms have been removed for clarity and the enclosed CF 3SO 3Àis represented as spheres.92Fig.13Stick representation of dichloro-substituted tetraoxacalix[2]-arene[2]triazine receptor forming a ternary complex with H 2O and Cl À.114C is colored gray,Cl green,N blue,O red and H white.Tetra-n -ethyl ammonium cations and one disordered O were removed for clarity.3148|mun.,2009,3143–3153This journal iscThe Royal Society of Chemistry 20094.A structural and computational study of the interaction of halides with electron-deﬁcient aromatic ringsWhile we were encouraged by our initial success in designing a system to measure anion–arene interactions in solution,we were frustrated with the ambiguity that surfaced by incorpor-ating two diﬀerent interaction types into one receptor.The next logical step was to remove additional supporting inter-actions and focus exclusively on anion–arene interactions.The subsequent section focuses on the interaction of anions with only electron-deﬁcient aromatic rings and provides solid state and computational scrutiny that redirects the focus of anion–arene interactions from centered electrostatic interactions to oﬀ-center weakly covalent s complexes.Having an accurate model for predicting the geometry of complexes between anions and electron-deﬁcient arenes is vital to the design of receptors incorporating these interactions.Thediscrepancy we and others were noting between theory and experiment,coupled with the general paucity of structural data for‘‘centered’’anion–p interactions with arenes,prompted us to undertake further investigations.Most of the initial theoretical studies focused primarily on the electrostatic anion–p interaction,in which the anion is positioned over the centroid of the arene.The earlier work by Kochi and co-workers,however,suggested that a CT binding motif may be operating in these systems,based on the intense color changes observed in their complexes.74By deﬁnition a predominantly electrostatic anion–p interaction would exhibit negligible CT(Fig.3,A).Solid state investigations of anion–arene interactionsOur research to this end began with a solid state investigation of the geometry of halide–arene interactions.Single crystals suitable for X-ray diﬀraction were grown from acetonitrile–dichloromethane solutions of alkali halides(KBr,KI and NaI), 1,2,4,5-tetracyanobenzene(TCB)and18-crown-6.Interestingly, each of these components is colorless when dissolved individually in organic solutions;however,when mixed together colored solutions are obtained with the color dependent on which halide is present.These colored solutions are consistent with previous studies and suggest that the operative binding mode is a CT or weak s interaction.Speciﬁcally,when KBr is present a bright yellow solution is obtained producing orange single crystals while NaI or KI produces red solutions and purple single crystals.When single crystals from these experiments were analyzed by X-ray diﬀraction it revealed four distinct interactions between each halide and diﬀerent TCB molecules(Fig.14).Much to our surprise the anion was positioned over the periphery of the arene rings rather than over the center as would be anticipated for electrostatic bonding.Halide–carbon distances range from 3.34to3.73A for BrÀand3.45to3.90A for IÀ. Computational investigations of anion–arene interactionsOur subsequent investigations sought to address the discrepancies in binding geometries we were observing between previous computational studies and our crystal structures.To accomplish this task we turned to high level quantum calculations of charge neutral electron-deﬁcient aromatic rings with halide anions.Four distinct anion geometries were observed from these calculations and are pictorially represented in Fig.3.The three possible geometries with the anion located above the plane of the aromatic ring can be described by the amount of covalent character present in the interaction.Anion–p interactions are by deﬁnition primarily electrostatic with the anion positioned above the centroid of the aromatic ring (Fig.3,A).Alternatively we have shown that in many cases the anion prefers to adopt a position over the periphery of the aromatic ring.We phrase these oﬀ-center attractions as weak s interactions(Fig.3,B and C),which are composed of considerably more covalent character than the anion–p interactions.The last anion–arene interaction that we calculated was an aryl C–H hydrogen bond with the anion located in the same plane as the aromatic ring(Fig.3,D).It is important to note that three of the calculated geometries(Fig.3,B–D)are the same as those that are observed in our crystal structures(Fig.14). In collaboration with Dr Benjamin P.Hay and Dr Vyacheslav S.Bryantsev,electronic calculations at the MP2/aug-cc-pVDZ level of theory were performed to evaluate the structure and interaction energies of1:1complexes formed between the arenes TCB,1,3,5-triazine and hexaﬂuorobenzene and the halides FÀ,ClÀand BrÀ.Interestingly,when calculations were performed with the nucleophilic FÀit was observed that the only stable geometry with the anion located over the ring is a strongly covalent s complex with the FÀlocated at the ring periphery.These complexes are distinguished by the large amount of charge-transfer from the anion to the electron-deﬁcient aromatic ring.Calculations with the less nucleophilic ClÀand BrÀshowed that weakly covalent s complexes are formed.These complexes contain binding geometries that are consistent with a smaller degree of covalent character. Halide–arene distances were longer(2.6to3.1A)and the carbon atoms remained nearly planar.The only stable geometry observed for ClÀwith all aromatic rings studied except C6F6was the weak s interactions with the halide located over the edge of the arene.BrÀexhibits the same behavior while also forming a stable anion–p complex with 1,3,5-tricyanobenzene.Calculations concerning either ClÀor Fig.14Single crystal structures of TCB with BrÀ(left)and IÀ(right) highlighting the anion positioned over the edge of the arenes.73This journal is c The Royal Society of mun.,2009,3143–3153|3149。

brifing in bioinformatics 模板

BRIEFING IN BIOINFORMATICSBIOINFORMATICS is a rapidly growing field that uses computer and information science methods to study biological data. It has become an essential part of modern biology, allowing researchers to analyze vast amounts of data and generate new insights. In this article, we will provide a brief introduction to bioinformatics, including its applications, tools, and resources.BIOINFORMATICS APPLICATIONSBioinformatics has a wide range of applications across biology, including genomics, proteomics, transcriptomics, and metagenomics. Here are some examples:1. Genomics: Sequencing and analysis of entire genomes, identification of genetic variants, and studies of population genetics.2. Proteomics: Characterization of protein expression, post-translational modifications, and interactions with other proteins.3. Transcriptomics: Analysis of RNA expression levels and alternative splicing events in different tissues and conditions.4. Metagenomics: Study of microbial communities in various environments, including the human microbiome.BIOINFORMATICS TOOLSBioinformatics tools are used to process, analyze, and visualize biological data. Here are some commonly used tools:1. Sequencing Read Manipulation Tools: Such as FASTQ/A Utils and Picard Tools for quality control, trimming, and alignment of sequencing reads.2. Genome Annotation Tools: Such as GATK, Augustus, and MAKER for gene prediction and annotation of whole genomes.3. Comparative Genomics Tools: Such as Mauve, BLAST, and HMMER for sequence alignment and identification of conserved protein domains.4. Visualization Tools: Such as Integrative Genomics Viewer (IGV), Tablet, and Circos for exploration andinterpretation of large-scale datasets.BIOINFORMATICS RESOURCESThere are numerous resources available for bioinformatics education and training, including:1. Online Courses: Many universities and institutions provide free or paid online courses in bioinformatics, such as Coursera's "Genome Science" series or edX's "Bioinformatics: Algorithms for Analyzing Biological Data" course.2. Tutorials and Workshops: Many bioinformatics software and tools provide detailed documentation and tutorials, such as the Galaxy Project's documentation or the GATK Best Practices guide. Additionally, many conferences and workshops provide training on specific topics.3. Public Databases: Such as NCBI's GenBank and Ensembl, as well as protein databases like UniProt, provide a wealth of information for bioinformatics research.4. Communities of Practice: These include bioinformatics-specific mailing lists, such as the Galaxy Helpdesk or theGATK forum on BioStar, as well as preprint servers like bioRxiv for sharing and discussing unpublished research. 5. MOOCs (Massive Open Online Courses): These courses are open to anyone with an internet connection and provide an opportunity to learn from top experts in the field, such as the XSeries on bioinformatics at Coursera or the University of Washington's Introduction to Bioinformatics course on edX.6. Books: There are several excellent textbooks available for bioinformatics education, including "Biological Data Analysis: The Complete Workflow" by Michael Brudno et al., "Bioinformatics: A Practical Guide to the Analysis of Genes and Proteins" by John Cummings et al., and "Introduction to Bioinformatics" by Pavel Pevzner et al.。

(英文)合成,与DNA和两个新的铜(II)的抗增殖活性相互作用配合甲斑蝥素和苯并咪唑衍生物

Synthesis,interaction with DNA and antiproliferative activities of two novel Cu(II)complexes with norcantharidin and benzimidazolederivativesWen-Ji Song a ,b ,Qiu-Yue Lin a ,b ,⇑,Wen-Jiao Jiang b ,Fang-Yuan Du b ,Qing-Yuan Qi b ,⇑,Qiong Wei ba Zhejiang Key Laboratory for Reactive Chemistry on Solid Surfaces,Zhejiang Normal University,321004,PR China bCollege of Chemical and Life Science,Zhejiang Normal University,321004,PR Chinah i g h l i g h t sTwo novel Cu(II)complexes withnorcantharidin derivatives have been synthesized.Complexes structure was determined by X-ray diffraction.The complexes and ligands bound DNA moderately via partial intercalation modes.Complexes could cleave plasmid DNA via hydroxyl radical mechanism. Complex(1)has strongest activity against human hepatoma cells.g r a p h i c a l a b s t r a c tTwo novel complexes [Cu(L)2(Ac)2]Á3H 2O(1)(L =N-2-methyl benzimidazole demethylcantharate imide,C 15H 13N 2O 3,Ac =acetate,C 2H 3O 2)and [Cu(bimz)2(DCA)](2)(bimz =benzimidazole,C 7H 6N 2;DCA =dem-ethylcantharate,C 8H 8O 5)were synthesized and characterized.The DNA-binding properties of complexes were investigated by electronic absorption spectra,ﬂuorescence spectra,viscosity measurements and agarose gel electrophoresis.The interaction between the complexes and bovine serum albumin (BSA)was investigated by ﬂuorescence spectra.The antiproliferative activities of the complexes against human hepatoma cells (SMMC7721)were tested in vitro .a r t i c l e i n f o Article history:Received 23June 2014Received in revised form 17August 2014Accepted 23August 2014Available online 1September 2014Keywords:NorcantharidinBenzimidazole derivatives Copper complex DNA bindingAntiproliferative activitya b s t r a c tTwo novel complexes [Cu(L)2(Ac)2]Á3H 2O (1)(L =N-2-methyl benzimidazole demethylcantharate imide,C 16H 15N 3O 3,Ac =acetate,C 2H 3O 2)and [Cu(bimz)2(DCA)](2)(bimz =benzimidazole,C 7H 6N 2;DCA =dem-ethylcantharate,C 8H 8O 5)were synthesized and characterized by elemental analysis,infrared spectra and X-ray diffraction techniques.Cu(II)ion was four-coordinated in complex 1,Cu(II)ion was ﬁve-coordi-nated in complex 2.A large amount of intermolecular hydrogen-bonding and p –p stacking interactions were observed in these complex structures.The DNA-binding properties ofthese complexes were inves-tigated using electronic absorption spectra,ﬂuorescence spectra,viscosity measurements and agarose gel electrophoresis.The interactions between the complexes and bovine serum albumin (BSA)were investi-gated by ﬂuorescence spectra.The antiproliferative activities of the complexes against human hepatoma cells (SMMC7721)were tested in vitro .And the results showed that these complexes could bind to DNA in moderate intensity via partial intercalation,and complexes 1and 2could cleave plasmid DNA through hydroxyl radical mechanism.Title complexes could effectively quench the ﬂuorescence of BSA through/10.1016/j.saa.2014.08.0691386-1425/Ó2014Elsevier B.V.All rights reserved.⇑Corresponding authors.Address:Zhejiang Key Laboratory for Reactive Chemistry on Solid Surfaces,Zhejiang Normal University,321004,PR China (Q.Y.Lin).Tel.:+8657982283353;fax:+8657982282269.E-mail addresses:sky51@ (Q.-Y.Lin),Qingyuanqi@ (Q.-Y.Qi).static quenching.Meanwhile,title complexes had stronger antiproliferative effect compared to L and Na2(DCA)within the tested concentration range.And complex1possessed more antiproliferative active than complex2.Ó2014Elsevier B.V.All rights reserved.IntroductionIn recent years,the interactions of Cu(II)complexes with DNA and protein molecules drew more and more scholars’attention [1,2].Copper(II)complexes are well suited for DNA hydrolysis due to the strong Lewis acid properties of the cupric ion.Several copper(II)complexes have been developed as artiﬁcial nucleases, and showed versatile DNA cleavage properties in the absence or presence of a redox agent[3,4].Planar heterocyclic based complexes have received consider-able interest in nucleic-acid chemistry because of their diverse chemical reactivity,unusual electronic properties,and peculiar structure,which results in non-covalent interactions with DNA [5].Benzimidazole derivatives possess a variety of biological activ-ities and pharmacological effects.Several compounds containing benzimidazole group,have been reported to exhibit antimicrobial, anticancer,antifungal and anti-inﬂammatory activities[6]. Especially,the combinations of the pharmaceutical agents with some metal ions can further improve their biological activity.Demethylcantharidin(NCTD,7-oxabicyclo[2,2,1]heptane-2,3-dicarboxylc acid anhydride)and disodium demethylcantharate (Na2(DCA)),as the derivatives of cantharidin,have been applied in clinical use[7].Meanwhile,demethylcantharate(DCA)could inhibit the activities of protein phosphatases1(PP1)and2A(PP2A)effec-tively[8,9].A range of amines were applied to react with norcantha-ridin,and results showed high level of cytotoxicity[10,11].Based on our previous investigations and as a continuation of our research program on complexes containing demethylcanthari-din[12,13],we synthesized two novel Cu(II)complexes containing demethylcantharidin.The interactions of these complexes with DNA and bovine serum albumin(BSA)were investigated.In addi-tion,antiproliferative activities against human hepatoma cells (SMMC-7721)were tested in vitro.Experimental sectionsMaterials and instrumentsAll reagents and chemicals were obtained from commercial sources.Demethylcantharidin(NCTD,C8H8O4)was obtained from Nanjing Zelang Medical Technology Co.Ltd.;Na2(DCA)was prepared in accordance with the literature described technique[14];2-ami-nomethylbenzimidazole dihydrochloride(ambiÁ2HCl)was pre-pared using the literature technique[15];benzimidazole(bimz, C7H6N2)and ct-DNA were obtained from Sinopharm Chemical Reagent Co.Ltd.;ct-DNA(q=200l g mLÀ1,c=3.72Â10À4mol LÀ1), with A260/A280=1.8–2.0,was prepared using50mmol LÀ1NaCl; Plasmid DNA(pDsRed2-C1)was purchased from Clontech Co.Ltd. America;Bovine Serum Albumin(BSA)was purchased from Beijing BioDee BioTech Co.Ltd.and was stored at4°C;BSA(q= 500l g mLÀ1,c=7.47Â10À6mol LÀ1)was prepared using 5mmol LÀ1NaCl solution;MTT(methyl thiazolyl tetrazolium)was purchased from the Sigma Company;Human hepatoma cells (SMMC-7721)was purchased from Shanghai Institute of Cell Bank. Other chemical reagents in analytical reagent grade were used with-out further puriﬁcation.Elemental analyses of C,H and N were carried out in Vario EL III elemental analyzer.Infrared spectra were obtained using the KBr disc method by NEXUS-670FT-IR spectrometer in the spectral range of4000–400cmÀ1.Diffraction intensities of the complexes were collected at293K on Bruker SMART APEX II CCD diffractom-eter.Electronic absorption spectra were obtained using UV-2501 PC spectrophotometer.Viscosity experiments were carried on Ubbelodhe viscometer.Fluorescence emission spectra were obtained by Perkin–Elmer LS-55spectroﬂuorometer.Agarose gel electrophoresis was performed on PowerPac Basic electrophoresis apparatus(BIO-RAD).Gel image formation were obtained on UNI-VERSAL HOOD11-S.N.(BIO-RAD Laboratories).Synthesis of LN-2-methyl benzimidazole demethylcantharate imide (L=C16H15N3O3)was prepared in accordance to the literature tech-niques[16].Mixture of1mmol norcantharidin(NCTD),1mmol2-aminomethylbenzimidazole dihydrochloride,1mmol cadmium acetate,and10mL distilled water was sealed in a25mL Teﬂon-lined stainless vessel and heated at433K for3d,then cooled slowly to room temperature.The solution was thenﬁltered and was allowed to stand still for3weeks until forming colorless crystals.Anal.Calcd. (%)for C16H15N3O3:C,64.65;H,5.05;N,14.14.Found(%):C,64.62;H, 5.03;N,14.16.IR(KBr pellet,cmÀ1):1617,1392(t(C@O));1446 (t(C@N));1258,1033,1001(t(C A O A C)).Synthesis of the complexesSynthesis of the complex1In a20mL weighing bottle,Cu(Ac)2ÁH2O(0.06g,0.3mmol)was dissolved in water(2mL).The L(0.089g,0.3mmol)solution in mixed solvents of water and ethanol(2:1,v/v)(10mL)was then added dropwisely with stirring under room temperature.The mix-ture solution wasﬁltered after two hours.One week after,blue crystals with suitable size for single-crystal X-ray diffraction were obtained.Anal.Calcd.(%)for C36H42N6O13Cu(1):C,52.05;H,5.06; N,10.12.Found(%):C,52.01;H,5.03;N,10.29.IR(KBr pellet, cmÀ1):3445(t(OH));1572,1395(t(C@O));1464(t(C@N));1254, 1057,984(t(C A O A C)).Synthesis of the complex2A mixture of Cu(Ac)2ÁH2O(0.5mmol)and Na2DCA(0.5mmol) was dissolved in water.And1.0mmol benzimidazole(bimz)in ethanol was added dropwisely into the mixed solution and stirring at room temperature.The solution wasﬁltered after two hours. One week later,blue crystals with suitable size for single-crystal X-ray diffraction were obtained.Anal.Calcd.(%)for Cu(C22H20 N4O5)(2):C,54.55;H,4.13;N,11.57.Found(%):C,54.25;H, 4.01;N,11.78.IR(KBr pellet,cmÀ1):3432(t(OH));1635,1396 (t(C@O));1432(t(C@N));1251,1032,981(t(C A O A C)).DNA bindingElectronic absorption spectraElectronic absorption spectra were collected at25°C byﬁxing the concentrations of the complexes,with DNA concentration ranging from0to7.44Â10À5mol LÀ1.Absorption spectra mea-surements were carried out at200–400nm,and DNA in Tris–HCl buffer solution(pH=7.4)was used as reference.W.-J.Song et al./Spectrochimica Acta Part A:Molecular and Biomolecular Spectroscopy137(2015)122–128123Fluorescence spectraFluorescence quenching experiments were carried out by add-ing DNA solutions(0–7.44Â10À4mol LÀ1)to the samples contain-ing2.00Â10À5mol LÀ1complexes.The mixture were diluted by Tris–HCl buffer solution(pH=7.4).Fluorescence for1was recorded at excitation wavelength(k ex)of248nm and emission wavelength(k em)between250nm and500nm.Fluorescence for 2was recorded at244nm excitation wavelength(k ex)and emis-sion wavelength(k em)between255nm and450nm(k em).Viscosity measurementViscosity measurements were pounds were added to DNA solution(3.72Â10À4mol LÀ1)with microsyringes. The concentration of the compounds were controlled within the range of0–3.33Â10À6mol LÀ1.The relative viscosities g were cal-culated using equation[17]:g=(t–t0)/t0,where t0and t represent theﬂow time of DNA solution through the capillary in the absence and presence of complex.The average values of three replicated measurements were used to evaluate the viscosity of the samples. Data were presented as(g/g0)1/3versus the ratio of the concentra-tion of compounds to DNA,where g was the viscosity of DNA in the presence of compound and g0was the viscosity of DNA. Interaction with pDsRed2-C1plasmid DNAInteractions between the complexes and pDsRed2-C1plasmid DNA were studied using agarose gel electrophoresis.The samples were incubated at37°C for3h,followed by addition of0.25% bromo-phenol blue and1mmol LÀ1EDTA.The DNA cleavage prod-ucts were submitted to electrophoresis in1.0%agarose gel contain-ing0.5l g mLÀ1ethidium bromides.The bands were photographed.Interaction with BSAFluorescence spectraThe complexes(0–26.7Â10À9mol LÀ1)were added to solution containing4.98Â10À7mol LÀ1BSA and Tris–HCl buffer(pH=7.4). Fluorescence spectra were obtained by recording the emission spectra(285–480nm)at excitation wavelength of280nm.Antiproliferative activity evaluationThe antiproliferative activities of the compounds(1,2,L and Na2(DCA))were evaluated by human hepatoma cells(SMMC-7721).The MTT assay was applied to measure the antiproliferative activities[18].The compounds were dissolved in DMSO as 100mmol LÀ1stock solutions,and diluted in culture medium before using.The target concentration of DMSO in the medium was less than0.1%,and it did not interfere with the tested bioactiv-ity results[19].Cells were seeded for24h before adding com-pounds,and incubated for72h.Then100l L MTT(1mg mLÀ1, dissolved in DMEM nutrient solution)was added into each well and incubated for4h(37°C).The absorbance was measured by microplate reader at570nm.The inhibition rate was calculated accordingly.The errors quoted were standard deviations,which three replicates were involved in the calculation[20].Crystal structure determinationSingle crystals,sized0.345mmÂ0.279mmÂ0.214mm(1) and0.345mmÂ0.287mmÂ0.156mm(2),were used for X-ray diffraction analysis.The structures were solved by direct methods and reﬁned by full-matrix least-squares techniques using the SHEL-XTL-97program package[21,22].All non-hydrogen atoms were reﬁned anisotropically.Besides the hydrogen atoms on oxygen atoms,which were located from the difference Fourier maps,other hydrogen atoms were generated geometrically.Crystal data and experimental details for structural analyses are listed in Table1. Results and discussionStructural description of complexesTwo novel complexes have been characterized by X-ray single crystal diffraction.The spectral results indicated that the space groups of the complexes were C2/C(1)and Pna21(2).Selected bond lengths and angles of complexes1,2were listed in Tables2and3. Hydrogen bond lengths and angles of complex1,2were listed in Tables S1and S2.Molecular structures of the title complexes were shown in Fig.1.The packing diagram was shown in Fig.S1.In complex1,the Cu(II)ion was four-coordinated.Each Cu(II) coordinated with two imine nitrogen N(2)(or N(2A))from ligand (L),and two oxygen atoms of different carboxyl groups from acetate ions,forming electrically neutral complex.This molecule was cen-trally symmetric,with the symcenter at the centre of CuN2O2.The bond angles of O(1)A Cu(1)A O(1)#1,O(1)A Cu(1)A N(2),O(1)#1A Cu(1)A N(2)#1and N(2)A Cu(1)A N(2)#1are88.38(14)°,90.23 (10)°,90.23(10)°and97.25(14)°,respectively,all of which are close 90°.Thus,a slightly distorted quadrangle was formed around Cu(1) by N(1),N(2),O(1),and O(3).The composition of the complex was [Cu(L)2(Ac)2]Á3H2O(1).Fig.S1showed that the hydrogen-bonding formed due to the presence of the nitrogen atoms and the oxygen atoms from the imide(L)and acetate ligands,and crystallization water molecules.The complex is rich in intramolecular and intermo-lecular hydrogen bonds,such as N(1)A H(1A)...O(1W);O(3W)A H(3WA)...O(4);O(2W)A H(2WA)...O(2).These hydrogen-bonding stabilized this crystal structure.In complex2,Cu(II)ion wasﬁve-coordinated.Each Cu(II)coor-dinated with two azomethine nitrogen N(1)(or N(3))from two bimz,two carboxylate oxygen atoms O2and O3in two different carboxylate groups,and one bridge oxygen atoms O1from dem-ethylcantharate,forming a distorted tetragonal pyramid structure. The composition of the complex was[Cu(bimz)2(DCA)](2).Fig.S1 showed that the hydrogen-bonding formed due to the presence of the nitrogen atom from the bimz and the oxygen atoms from demethylcantharate,such as N(2)A H(2A)...O(5)#1,N(4)A H(4A)... O(3)#2.Meanwhile,complexes1and2contain the benzimidazole group,resulting k–k stacking effects among the complexes.There-fore,we concluded that the synergistic effect,including p–p stack-ing and hydrogen-bonding interactions,existed between the complexes and biomacromolecule,which could be the fundamen-tal cause of the biological activity change found in macromolecules [23].DNA binding studiesElectronic absorption spectraThe application of electronic absorption spectroscopy is one of the most useful techniques in DNA-binding studies[24].Changes observed in the UV spectra upon titration can provide evidence for the intercalative interaction mode pattern,since hypochro-mism would occur from p–p stacking interactions[25].To further investigate the possible binding modes and to obtain the binding constants(K b)of complex to DNA,we also studied the effect of DNA titration to the title complexes by electronic absorption spec-tra at298K.Results are shown in Fig.2((a):1;(b):2).The intrinsic binding constant(K b)was determined by the equa-tion:[DNA]/(e A–e F)=[DNA]/(e B–e F)+1/[K b(e B–e F)],where[DNA] was the concentration of DNA,e A,e F and e B corresponded to the apparent extinction coefﬁcient,the extinction coefﬁcient for the124W.-J.Song et al./Spectrochimica Acta Part A:Molecular and Biomolecular Spectroscopy137(2015)122–128W.-J.Song et al./Spectrochimica Acta Part A:Molecular and Biomolecular Spectroscopy137(2015)122–128125Table1Crystal data of complex1and2.Complex12Chemical formula CuC36H42N6O13CuC22H20N4O5 Formula weight794.28483.97Crystal system Monoclinic Orthorhombic Space group C2/C Pna21a(Å)21.572(4)15.8667(3) b(Å)11.3687(19)9.9975(2)c(Å)17.371(4)12.5228(2) a(°)90.0090.00b(°)111.528(18)90.00c(°)90.0090.00Volume(Å3)3963.0(13)1986.46(6) Z44Crystal size(mm)0.345Â0.279Â0.2140.345Â0.287Â0.156 Shape Block BlockFig. beled ORTEP diagrams of complex1(a)and2(b)with30%thermalprobability ellipsoids shown.complexes1and2are quenched in presence of DNA.The plexes showed strong emission bands at around297nm(1 nm(2),as shown in Fig.3.According to the Stern–Volmer equation:F0/F=1+K sv[Q],F0and F represent theﬂuorescence intensities in the absence and presence of quencher,respectively [Q]is the quencher concentration and K sv is the Stern–Volmer constant,K sv were calculated as 4.26Â103mol LÀ1(1)Â103mol LÀ1(2).The binding intensity of complex1 stronger than complex2,this is consistent to the results found electronic absorption spectra.Viscosity measurementsfurther study the binding mode of the compounds interact-with DNA,DNA viscosity at25°C was investigated(Fig.experimental data showed that the relative viscosity of steadily decreased after adding complexes and L,and it increase after adding benzimidazole.But there was no signiﬁcant viscosity change occurred after adding Na2DCA.The possible expla-nation is that the complexes and L were partially inserted to DNA base pairs and resulting in a kink in the DNA helix,therefore decreased the DNA effective length[29].Because of the planar benzimidazole ring could also insert to the DNA base pair,and the steric hindrances of complexes were enhanced due to the non-planar structure of demethylcantharate(DCA).From Fig.4, the interactions of complex(1)with DNA is signiﬁcantly stronger than complex(2).The result agrees with the electronic absorption spectra andﬂuorescence spectra conclusion.Interaction with pDsRed2-C1plasmid DNAThe cleavage reaction on pDsRed2-C1plasmid DNA can be mon-itored by agarose gel electrophoresis.When pDsRed2-C1plasmid DNA is subjected to electrophoresis,different migration speeds were observed[30].Relatively fast migrations were observed at the intact supercoil form(Form I).If scission occurs on one strand (nicking),the supercoil will partially relax to generate a slow moving open-circular form(Form II)[31].Absorption spectra of the complex1(a)and2(b)in the presence of increasing amount of DNA.[complex]=3.00Â10À6mol LÀ1,from(1)to(5):Â105=0,0.74,1.48,2.24and2.98mol LÀ1,respectively.(b).[DNA]Â103.72,5.58and7.44mol LÀ1,respectively.3.Fluorescence spectra of the complex1(a)and2(b)in the absence presence of increasing the amount of DNA;insert in Figs.3–5:ﬂuorescence quenching curve of the complex by DNA.k ex=248nm(1),k ex=244nm [complex]=2Â10À5mol LÀ1;[DNA]/(10À4mol LÀ1),from1to5:0,1.86,3.72,7.44,respectively.4.Effect of increasing amounts of the compounds on the relative viscosity[DNA]=3.72Â10À4mol LÀ1;[complex]/10À6=0,0.67,1.33,2.00,2.67mol LÀ1,respectively.5gave the electrophoretograms of the interactionRed2-C1plasmid DNA with increasing concentrations of complexes. Complexes are capable of cleaving plasmid DNA when the concen-of complexes was greater than500l M.When the concentra-complexes increased,the amount of Form I diminished gradually,and Form II paring channel4–6, cleavage ability of complexes was enhanced by adding ascorbic order to investigate the reaction mechanism,dimethylsulfox-(DMSO)was introduced to the experimental design.DMSO scavenger could inhibit the cleavage ability of complexes signiﬁcantly in channel5and7.With increasing amount of acid(V c),Cu(II)complex was reduced to Cu(I)complex.complex then reacts with dissolved oxygen generating superoxide anion(O2À),hydrogen peroxide(H2O2)and hydroxyl (ÅOH).Finally,the ROS attacks the plasmid DNA leading single and double DNA strand breaks.So the cleavage hydroxyl radical mechanism[32].Interaction with BSAFluorescence spectra and quenching mechanismresults of title complexes quenching the BSAﬂuorescence ing,which generated via intense interaction[36].Binding constants and binding sitesAssuming there were n identical and independent binding sites in protein,the binding constant K A can be calculated using equation[37]:lg(F0–F)/F=lg K A+n lg[Q].The values of K A were 1.59Â106L molÀ1(1), 5.4Â104L molÀ1(2),and 2.78Â104L molÀ1(Na2DCA).The values of n were0.88(1),0.68(2)and 0.66(Na2DCA).The results indicated that strong bindingElectrophoretic separation of pDsRed2-C1DNA induced by complexesLane1:DNA alone;lane2:DNA+complex(250l M);lane3:DNA(500l M);lane4:DNA+complex(750l M);lane5:DNA++DMSO(750l M);lane6:DNA+complex(750l M)+V c(750complex(750l M)+V c(750l M)+DMSO(750l M).[DNA]=3.06.Fluorescence spectra of BSA in the absence and the presence of complex2(b)Inset:Stern–Volmer plots of theﬂuorescence titration data ofcomplexes.[BSA]=4.98Â10À7mol LÀ1;[complex]Â109=0,6.67,13.3,20.0,mol LÀ1,from(1)to(5),respectively(a):complex1,(b):complex2.7.Inhibition effects of compounds on SMMC-7721cell growth.Data representmean+S.D.and all assays were performed in triplicate for three independentexperiments.interaction existed between the complexes and BSA.The binding intensity of complexes was stronger than Na2DCA,and the binding site of complexes was one.Antiproliferative activity evaluationAs shown in Fig.7,the antiproliferative activity of complex1, complex2,L and Na2DCA at the given concentration showed a dose-dependent manner against human hepatoma cells(SMMC-7721)in vitro.The inhibition ratios tested revealed that complex1and2had strong antiproliferative activities against human hepatoma cells (SMMC-7721)lines in vitro compare to L and Na2DCA.The inhibi-tion rates of complex(1)against SMMC-7721lines(IC50=24.55±0.48l mol LÀ1)is much higher than that of L(IC50=116.63±2.66 l mol LÀ1)[38].The inhibition rates of complex(1)against SMMC-7721lines is much higher than complex(2)(IC50=41.82±3.90 l mol LÀ1).The inhibition rates of two novel complexes were higher than that of the transition metal complexes of demethyl-cantharate and thiazole derivatives[12,13]against SMMC-7721 cells.which suggests that various compositions and structures of complexes would lead to different antiproliferative activities,and this can be important in designing and synthesizing novel anti-cancer drugs[39].It is clear that the strong interaction found between complexes and biomacromolecules(DNA or BSA)is directly correlated to the antiproliﬁferative activity of complexes.ConclusionsTwo novel Cu(II)complexes[Cu(L)2(Ac)2]Á3H2O(1)(L=N-2-methyl benzimidazole demethylcantharate imide,C16H15N3O3, Ac=acetate,C2H3O2)and[Cu(bimz)2(DCA)](2)(bimz=benzimid-azole,C7H6N2;DCA=demethylcantharate,C8H8O5)were synthe-sized and characterized.The crystal structure of complex1and2 were determined by X-ray diffraction.These complexes had strong DNA and BSA binding intensity and high inhibition rates against human hepatoma cells(SMMC-7721)in plex(1)had intense antiproliferative activities against the human hepatoma cells(SMMC-7721)in vitro,which had the potential to develop as an anti-cancer drug in the future.AcknowledgmentWe thank Institute of Zhejiang Academy of Medical Science for helping with antiproliferative activity test.Appendix A.Supplementary materialCrystallographic data for the structure reported in this article has been deposited with the Cambridge Crystallographic Data Center CCDC909444(1),918105(2).Copies of the data can be obtained free of charge on application to the CCDC,12Union Road,Cambridge CB21EZ,UK(deposit@).The packing diagrams of complexes were shown in Fig.S1.Hydrogen bond lengths and angles of complex1,2were listed in Tables S1and S2.Supplementary data associated with this article can be found,in the online version,at 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rqcen化学讲义

rqcen化学讲义（中英文实用版）英文文档：The RQCEN Chemistry Lecture Notes provide an overview of the fundamental principles and concepts in chemistry.The lecture notes are designed to serve as a comprehensive resource for students studying chemistry at the high school or undergraduate level.The first section of the lecture notes covers the basic building blocks of matter, including atoms, molecules, and ions.It also discusses the periodic table of elements, which is organized based on their atomic number and electron configuration.The second section focuses on chemical bonding and molecular structure.It explains the different types of chemical bonds, such as ionic, covalent, and metallic bonds, and describes the factors that influence bond strength and stability.The section also covers the VSEPR theory, which is used to predict the molecular geometry of molecules based on the number of bonding and non-bonding electron pairs around the central atom.The third section delves into the properties of matter, including physical and chemical properties.It discusses the concepts of solubility, boiling point, melting point, and density, and explains how these properties can be used to identify and characterize substances.The fourth section covers the principles of chemical reactions, including stoichiometry, reaction rates, and equilibrium.It explains how to balance chemical equations, calculate the amount of product formed in a reaction, and determine the rate at which a reaction occurs.The section also discusses Le Chatelier"s principle, which describes how changes in temperature, pressure, and concentration can affect the equilibrium of a chemical reaction.The fifth section explores the applications of chemistry in various fields, such as medicine, environmental science, and industry.It discusses the development of new drugs, the impact of chemical pollutants on the environment, and the use of catalysts in industrial processes.Overall, the RQCEN Chemistry Lecture Notes provide a comprehensive introduction to the study of chemistry, covering the fundamental principles and concepts that are essential for further study in the field.中文文档：RQCEN化学讲义提供了化学基本原理和概念的概述。

译文Bioconjugate Technique

Zero-Length Cross-linkersThe smallest available reagent systems for bioconjugation are the so-called zerolength有效试剂生物偶联所谓的零长度cross-linkers. These compounds mediate the conjugation of two molecules by 交联剂化合物调解结合2molforming a bond containing no additional atoms. Thus, one atom of a molecule is 形成键包含额外的原子分子covalently attached to an atom of a second molecule with no intervening linker or 共价结合干预链接器spacer. In many conjugation schemes, the final complex is bound together by virtue of间隔方案合成绑定在一起凭借chemical components that add foreign structures to the substances being cross-linked.成分结构体成分In some applications, the presence of these intervening linkers may be detrimental to 应用存在介入的连接器有害的the intended use. For instance, in the preparation of hapten-carrier conjugates the 预期用途例如制备了半抗体载体轭化物complex is formed with the intention of generating an immune response to the attached hapten. 复杂形成生成的意图免疫反应附加的Occasionally, a portion of the antibodies produced by this response偶尔一份抗体产生反应will have specificity for the cross-linking agent used in the conjugation procedure.特异性药剂结合过程Zero-length cross-linking agents eliminate the potential for this type of cross-reactivity消除潜在的交叉反应by mediating a direct linkage between two substances.中介直接联系化学成分The reagents described in this chapter can initiate the formation of three types of 本章描述的试剂开始形成bonds: an amide linkage made by the condensation of a primary amine with a carboxylic acid, a 酰胺键压缩伯胺羧酸phosphoramidate linkage made by the reaction of a organic phosphate氨基磷酸酯有机磷酸盐的反应group with a primary amine, and a secondary or tertiary amine linkage made by the伯胺二级或三级胺reductive amination of a primary or secondary amine with an aldehyde group. Therefore, using 还原氨化反应一级或二级胺醛基these reagent systems, substances containing amines can be conjugated试剂含胺类物质结合的with other molecules containing phosphates or carboxylates. Alternatively, substances含磷酸盐羧化物二选一containing amines can be cross-linked to molecules containing formyl groups. All of含胺含甲酰组the reactions are quite efficient, and depending on the reagent chosen and the desired 反应非常有效根据不同的试剂想要的application, they may be performed in aqueous or nonaqueous environments.应用在水或非水溶剂环境中执行1.Carbodiimides碳化二亚胺Carbodiimides are used to mediate the formation of amide linkages between a carboxylate and an amine or phosphoramidate linkages between a phosphate and an amine碳化二亚胺用于调解的形成酰胺羧酸盐和胺之间的联系或氨基磷酸酯和磷酸盐和胺之间的联系(Hoare and Koshland, 1966; Chu et al., 1986; Ghosh et al., 1990).They are probably the most popular type of zero-length cross-linker in use,可能最受欢迎的类型的长度为零的交联使用,being efficient in forming conjugates between two protein molecules, between a peptide and a protein,在两个蛋白质分子之间形成配合,肽和蛋白质,between oligonucleotides and proteins, or any combination of these with small mole cules. There are two basic types of carbodiimides: water-soluble and water-insoluble.寡核苷酸和蛋白质之间,或与小摩尔cul。

Analog Integrated Circuits And Signal Processing

ANALOG INTEGRATED CIRCUITS AND SIGNAL PROCESSING
An International Journal
Volume 9, No. 2, March 1996
Translinear rcuits in Subthreshold MOS
..............
Andreas G. Andreou and Kwabena A. Boahen'
141
PHOTOCOPYING.In the U.S.A.: Thisjournal is registered at the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, U.S.A. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Kluwer Academic Publishers for users registered with the Copyright Clearance Center (CCC) Transactional Reporting Service, provided that the base fee of $8.50 per copy per article is paid directly to CCC. For those organizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged. The fee code for users of the Transactional Reporting Service is 09251030/95/$8.50. Authorization does not extend to other kinds of copying, such as that for general distribution, for advertising or promotional purposes, for creating new collective works, or for resale. In the rest of the world: Permission to photocopy must be obtained from the copyright owner. Please apply to Kluwer Academic Publishers, P.O. Box 17,3300 AA Dordrecht, The Netherlands.

2016 SID 74-1 混合显示柔性OLED+反射式液晶-----日本半导体能源所

Application of Transfer Technology to Manufacturing of Transmissive OLED and Reflective LC Hybrid (TR-Hybrid) Display Takayuki Ohide*, Seiji Yasumoto*, Masataka Nakada*, Hiroki Adachi*, Satoru Idojiri*, Kenichi Okazaki*, Yoshiharu Hirakata**, Johan Bergquist**, and Shunpei Yamazaki***Advanced Film Device Inc., Tochigi, Japan**Semiconductor Energy Laboratory Co., Ltd., Kanagawa, JapanAbstractOur previously established transfer technology using an inorganic separation layer was applied to enable a novel through electrode structure including a conductive material exposed after separation. Using this structure, we succeeded in fabricating a transmissive OLED and reflective LC hybrid display.Author KeywordsTR-Hybrid display; through electrode structure; reflective LCD; OLED display; inorganic separation layer; transfer technology.1. IntroductionRecently, small- to medium-sized mobile devices such as smartphones and tablet PCs have become increasingly popular. Such mobile devices require some of the same properties as general displays, including high image quality and moving image function, and low power consumption. With a focus on reducing power consumption, we fabricated a display that includes two types of display devices between two glass substrates. This display exhibits sufficient display quality in both the reflective and transmissive modes. However, the general structure of the display requires four glass substrates to bond an organic light-emitting diode (OLED) panel to a reflective liquid-crystal display (LCD) panel, making the product heavy. Moreover, since the light-emitting portion of the structure is far from the opening, the light-extraction efficiency cannot be improved.We fabricated a semiconductor device on our novel through electrode structure in which a pixel, terminal, and common contact are exposed after separation through the inorganic-separation-layer process. The combination of the through electrode structure and OLED and reflective LCD processes enabled the fabrication of a display that includes a reflective LCD and an OLED between two glass substrates. In this structure, the distance between a light-emitting portion and the opening is several micrometers or smaller, leading to an improvement in light-extraction efficiency or a reduction in power consumption.This study applies a transfer technology [1–8] to establish a through electrode technique in which a conductive material serving as an electrode is exposed after separation. The through electrode technique is used to expose a pixel electrode, an extraction terminal, and a common contact of a device fabricated over a separation layer on a substrate after separation.2. Structure of TR-Hybrid DisplayFigure 1 is a schematic of a transmissive OLED and reflective LC hybrid (TR-Hybrid) display that includes two types of display devices between two glass substrates. In the pixel, a reflective LCD and a bottom-emission OLED are individually fabricated. To increase the visibility of the display with low power consumption, display is performed by the reflective LCD under outside light [9,10] and by the OLED in dark environments. The transfer technology and through electrode technique are employed for these two different display devices. The through electrode structure, which involves an electrode being exposed after separation, enables the OLED and LCD in the TR-Hybrid display to be driven by one circuit.Figure 1. Schematic of TR-Hybrid display.3. Application of Transfer Technology to ThroughElectrode StructureFigure 2 shows general flexibilization processes. We fabricated flexible displays using an inorganic-separation-layer process using a separation layer containing an inorganic material [6–8]. In the fabrication of a flexible display, the inorganic separation layer lies over a glass substrate, and a passivation layer lies on the flat surface of the separation layer. The passivation layer protects an element layer, which includes field-effect transistors (FETs) and wiring, and an organic electroluminescent layer over the element layer from moisture and oxygen. In the TR-Hybrid display, the passivation layer also protects FETs and an OLED from damage during the LCD process. Owing to the inorganic separation layer, the passivation and element layers can be formed in a general manufacturing process using a glass substrate, and high workability can be obtained. Furthermore, the process temperature can be as high as that for the general manufacturing process in which a glass substrate is used, which provides favorable FET characteristics and a high-quality passivation layer.74-1 / T. Ohide1002 • SID 2016 DIGEST ISSN 0097-966X/16/4702-1002-$1.00 © 2016 SIDFigure 2. Flexibilization processes.Our transfer technology uses a highly reliable passivation layer. By combining the through electrode structure and the inorganic-separation-layer process having these advantages, we developed FET boards for TR-Hybrid displays.Figure 3 provides an overview of the manufacturing process for a TR-Hybrid display employing the through electrode structure. As illustrated in Fig. 3(a), an inorganic separation layer and a passivation layer containing through electrodes are formed on a glass substrate. Subsequently, an FET element is formed through a general FET process. Then, a bottom-emission OLED that emits light through the FET is formed on the board (Fig. 3(b)). Figure 3(c) shows a structure in which the OLED panel is provided on the FET board including the through electrodes; a glass substrate lies beneath the OLED, and the highly reliable passivation layer lies above the OLED. Separation at the passivation–separation layer interface is performed by applying the transfer technology (Fig. 3(d)). Consequently, the glass substrate is separated, and the conductive materials that pass through the passivation layer are exposed. This enables the extraction of FET signals. Using the exposed electrode, extraction terminal, and common contact, the reflective LCD can be fabricated (Fig. 3(e)). Thus, a TR-Hybrid display with the OLED below the FET element and the LCD over the FET element is completed (Fig. 3(f)). As we can see from the structure, the display includes just two glass substrates for supporting the two types of display devices: the reflective LCD and the OLED.The separation force was evaluated using a compact table-top tester (EZ-Test, Shimadzu Corporation). Each sample for evaluation was fabricated as follows: a separation layer and a passivation layer were formed over a glass substrate, the substrate was then cut to dimensions of 25 mm 126 mm, and a film was bonded to the substrate. The perpendicular force required to separate the film was measured for each sample. Figure 4 shows the results for (a) the conventional structure and (b) the through electrode structure. The separation force required for the through electrode structure was similar to that for the conventional structure. This indicates that the through electrode structure can be formed through the conventional separation process.Figure 3. Schematics of manufacturing process ofTR-Hybrid display.Figure 4. Separation force results.74-1 / T. OhideSID 2016 DIGEST • 1003To manufacture the TR-Hybrid display, glass separation was performed after the formation of the OLED panel. Thus, the FET characteristics were evaluated before and after the separation (Figs. 5(a) and 5(b), respectively). No significant differences were observed in the FET characteristics, indicating that the separation did not affect the FET element. This suggests that favorable FET characteristics are retained after the separation process.(a) (b)Figure 5. FET (L/W= 3/3 μm) characteristics (a) before separation and (b) after separation.4. Fabrication of TR-Hybrid Display usingThrough Electrode StructureWe produced a prototype 4.38-inch TR-Hybrid display including a reflective LCD and an OLED using an FET board with the through electrode structure. Table 1 lists the display specifications. The pixel density was 292 ppi. Figure 6 shows photographs of the display. The display can be used in a reflective LCD mode in bright environments (outdoors) and in an OLED display mode in dark environments (indoors). The display can also be used in a hybrid mode, a combination of the two modes. We promote the development of large-sized panels and aim to achieve large and high-definition panels with low power consumption.Table 1. Display specifications.SpecificationScreen Diagonal 4.38 inchEffective Pixels 768 ⨯ RGB ⨯ 1024Pixel Pitch 29 μm ⨯ 87 μmPanel Size 76 mm ⨯ 140.1 mmPixel Density 292 ppiOLED Bottom-emissionOLED LCD ReflectiveLCD (a)(b)Figure 6. Photographs of prototype TR-Hybrid display(a) under outside light and (b) in dark environment.5. ConclusionBy applying a transfer technology using an inorganic separationlayer, we established a novel through electrode technique in whichan electrode is exposed after separation. The technique led to thesuccessful fabrication of a TR-Hybrid display in which an OLEDand a reflective LCD can be driven by one circuit. We expect thatthe application of the display technology will lead to thedevelopment of large-sized panels with high visibility underoutside light and low power consumption.6. References[1]R. Kataishi et al., SID Digest 45, 187 (2014).[2]Y. Jimbo et al., SID Digest 45, 322 (2014).[3]R. Komatsu et al., SID Digest 45, 326 (2014).[4] D. Nakamura et al., SID Digest 46, 1031 (2015).[5] A. Chida et al., SID Digest 44, 196 (2013).[6]S. Idojiri et al., SID Digest 46, 8 (2015).[7]K. Hatano et al., SID Digest 42, 498 (2011).[8]T. Aoyama et al., AM-FPD’13, 223 (2013).[9]S. Fukai et al., SID Digest 45, 1496 (2014).[10]D. Kubota et al., SID Digest 46, 1084 (2015).74-1 / T. Ohide1004 • SID 2016 DIGEST。

psectag2_man

Methods ......................................................................................................................... 2
Cloning into pSecTag2...........................................................................................................................................2 Transformation and Transfection.........................................................................................................................6 Expression and Purification ..................................................................................................................................8
Introduction ................................................................................................................... 1
Product Overview ..................................................................................................................................................1. V900-20

A Broadband CPW-to-Waveguide Transition Using Quasi-Yagi Antenna

III. SIMULATION AND MEASUREMENT RESULTS
The transition for the X-band prototype is simulated and optimized using both Ansoft and HP HFSS. Fig. 3 shows the simulation results of the back-to-back X-band transition. The simulation results do not include metal and dielectric loss. The result shows that return loss is below -10dB across all of X-band with maximum insertion loss of -0.2dB.
Email: kaneda@
ABSTRACT
A novel CPW-to-waveguide transition utilizing a uniplanar quasi-Yagi antenna is presented. The X-band back-to-back transition demonstrates 33% bandwidth with return loss better than -10dB. This transition should find a wide variety of applications due to its high MIC/MMIC compatibility and low cost.
A irb rid g e
S u b s tra te
C P W circuit p la n e

A review on the formation of titania nanotube photocatalysts by hydrothermal

ReviewA review on the formation of titania nanotube photocatalysts by hydrothermal treatmentChung Leng Wong,Yong Nian Tan,Abdul Rahman Mohamed *School of Chemical Engineering,Engineering Campus,Universiti Sains Malaysia,14300Nibong Tebal,Pulau Pinang,Malaysiaa r t i c l e i n f oArticle history:Received 14August 2010Received in revised form 15January 2011Accepted 6March 2011Available online 29March 2011Keywords:Titania nanotubesHydrothermal method MechanismStarting materialSonication pretreatment Hydrothermal temperaturea b s t r a c tTitania nanotubes are gaining prominence in photocatalysis,owing to their excellent physical and chemical properties such as high surface area,excellent photocatalytic activity,and widespread avail-ability.They are easily produced by a simple and effective hydrothermal method under mild temperature and pressure conditions.This paper reviews and analyzes the mechanism of titania nanotube formation by hydrothermal treatment.It further examines the parameters that affect the formation of titania nanotubes,such as starting material,sonication pretreatment,hydrothermal temperature,washing process,and calcination process.Finally,the effects of the presence of dopants on the formation of titania nanotubes are analyzed.Ó2011Elsevier Ltd.All rights reserved.1.IntroductionIn the environmental technology sector,industrial wastewater treatment is gaining importance for the removal of organic pollut-ants (Neves et al.,2009).Large amounts of organic pollutants consumed in the industries are being released into the eco-system over the past few decades and they constitute a serious threat to the environment (Mahmoodi and Arami,2009).As chemical and agri-cultural wastes,these contaminants are frequently carcinogenic and toxic to the aquatic system because of their aromatic ring structure,optical stability and resistance to biodegradation (Mahmoodi and Arami,2009).Catalytic technologies are gaining recognition in the ﬁeld of environmental protection (Yu et al.,2007b ).In past decades,the traditional physical techniques for the removal of organic pollut-ants from wastewaters have included adsorption,biological treat-ment,coagulation,ultra ﬁltration and ion exchange on synthetic resins (Mahmoodi and Arami,2009and Sayilkan et al.,2006).Those methods have not always been effective and they may not actually break down the pollutants in wastewater.For example,adsorption technology does not degrade the contaminants,but essentially transfers the contaminants from one medium to another,hence,contributing to secondary pollution (Mahmoodi and Arami,2009and Sayilkan et al.,2006).Moreover,such operations are expen-sive because the pollutants are treated before the adsorption process while the adsorbent medium has to be regenerated for re-use (Mahmoodi and Arami,2009).Traditional biological treatments are often ineffective in removing and degrading pollutants because the molecules,being mostly aromatic,are chemically and physically stable (Xu et al.,2009).Hence,biodegradation of organic pollutants is usually incomplete and selective (Xu et al.,2009).In fact,some of the degradation intermediates may be even more toxic and carci-nogenic than the original pollutants (Xu et al.,2009).Chlorination and ozonation have also been used in contaminant removal,but their operating costs are high compared with other methods (Sayilkan et al.,2006).Finally,although coagulation treatments using alums,ferric salts,or limes are inexpensive,they often pose waste disposal problems of their own (Mahmoodi and Arami,2009).With the discovery of photocatalytic splitting on TiO 2electrodes by Fujishima and Honda in 1972,heterogeneous photocatalysis has attracted much attention as a new puri ﬁcation technique for air and water (Fujishima and Honda,1972;Yu et al.,2006,Yu et al.,2007a and Yu et al.,2007b ).Heterogeneous photocatalysis has been successfully used in the oxidation,decontamination or minerali-zation of organic and inorganic contaminants in wastewater without generating harmful byproducts (Thiruvenkatachari et al.,2008).This approach has attracted much attention for its ease of*Corresponding author.Tel.:þ60045996410;fax:þ60045941013.E-mail address:chrahman@m.my (A.R.Mohamed).Contents lists available at ScienceDirectJournal of Environmental Managementjournal homepage:www.elsev /locat e/jenvman0301-4797/$e see front matter Ó2011Elsevier Ltd.All rights reserved.doi:10.1016/j.jenvman.2011.03.006Journal of Environmental Management 92(2011)1669e 1680application in oxidizing and degrading organic pollutants at rela-tively lower costs(Sayilkan et al.,2006).Currently,many semiconductors have been applied in hetero-geneous photocatalysis(Costa and Prado,2009).Semiconductor photocatalysts such as CdS,SnO2,WO3,TiO2,ZrTiO4,and ZnO (Nawin et al.,2008;Seo et al.,2001and Seo et al.,2009),titania (TiO2)semiconductor photocatalysts have demonstrated advan-tages that include transparency(Nawin et al.,2008),wide band gap (Wang et al.,2008),biological and chemical inertness(Lee et al., 2007;Mahmoodi and Arami,2009;Yu et al.,2006,Yu et al., 2007a,Yu et al.,2007b and Zhang et al.,2010),strong oxidizing power(Lee et al.,2007;Yu et al.,2006and Yu et al.,2007a)and non-toxicity(Lee et al.,2007;Mahmoodi and Arami,2009;Neves et al., 2009;Yu et al.,2006,2007a and Zhang et al.,2010).Considerable effort has been made to develop TiO2semi-conductor photocatalysts for environmental protection procedures such as air and water puriﬁcation(Lee et al.,2007;Nawin et al., 2008;Yu et al.,2006and Yu et al.,2007b),antibacterial protec-tion(Vuong et al.,2009),water disinfection(Yu et al.,2006and Yu et al.,2007b),treatment of harmful gas emission(Nawin et al., 2008)and hazardous water remediation(Yu et al.,2006and Yu et al.,2007b).TiO2has been used in many areas such as in photo-catalysis,in the generation of hydrogen from water(photocatalytic water splitting),in photocatalytic oxidation of organic or inorganic compounds,and in solar cells.Despite the enormous potential of TiO2semiconductor photocatalysts,its low efﬁciency limits its role in present day photooxidation technology(Lee et al.,2007;Yu et al., 2006and Yu et al.,2007a).Thus,signiﬁcant improvements and optimizations to TiO2semiconductor photocatalysts are needed before their many promising applications can be realized(Yu et al., 2006and Yu et al.,2007a).With appropriate modiﬁcation and optimization,TiO2semiconductor photocatalysts can be develop to generate active charge carriers to degrade organic pollutants into the harmless products(Yu et al.,2006).The performance of TiO2semiconductor photocatalysts is strongly inﬂuenced by the physical and chemical properties that determine its morphology,dimension and crystallite phase(Vuong et al.,2009).From research carried with TiO2nanocrystals,it has been shown that the smaller particle size(giving rise to larger surface area-to-volume ratio)of TiO2nanocrystals increases pho-tocatalytic efﬁciency(Wang et al.,2008and Yu et al.,2007a).The disadvantages of TiO2semiconductor photocatalysts include the requirement of large amounts of TiO2semiconductor photo-catalysts,difﬁculty in re-cycling TiO2semiconductor photocatalysts, problems encountered in its recovery byﬁltration or centrifugation, and the problematic agglomeration of TiO2nanocrystals into large particles(Costa and Prado,2009;Gupta et al.,2006and Ribbens et al.,2008).The separation processes required to recover the TiO2 semiconductor photocatalysts at the end of the photocatalytic treatment are difﬁcult to perform because of the small size of the TiO2semiconductor photocatalysts and the high stability of the TiO2 semiconductor photocatalyst hydrocolloid(Costa and Prado,2009). TiO2semiconductor photocatalysts also have the tendency to lose efﬁciency when they agglomerate into larger particles(Ribbens et al.,2008).This also adds to the complications in their disposal. While immobilized TiO2nanocrystals are an option for large scale application,the overall photocatalytic efﬁciency is compromised due to the reduction in surface area and the limitation in mass transfer(Yu et al.,2007a).To overcome these difﬁculties,different titanate nanostructure preparations are being investigated with the aim of increasing photocatalytic efﬁciency(Costa and Prado,2009 and Okour et al.,2009).Nanostructured materials such as nanoﬁbers,nanoparticles, nanorods,nanospheres,nanotubes and nanowires present new features and opportunities for enhanced performance in many promising applications(Costa and Prado,2009;Seo et al.,2009; Wang et al.,2007and Wang et al.,2008).Nanostructured mate-rials are of special signiﬁcance owing to their excellent physi-cochemical properties that are catalytic,electronic,magnetic, mechanical and optical in nature(Poudel et al.,2005).They are widely applied in air and water puriﬁcation technologies,photo-catalysis,gas sensors,high effect solar cells and microelectronic devices(Nakahira et al.,2004and Yu and Yu,2006).For example, O’Regan et al.stated that titania nanotubes have been used in high quality,efﬁcient solar cells(Nakahira et al.,2004).Nanostructured materials with different morphologies have varying speciﬁc prop-erties and,hence,the new applications of such materials are related to the shape and size of the nanostructured materials(Wang et al., 2007).The synthesis of nanostructured materials with speciﬁc shape and size,as well as the understanding of their formation mechanism are two important research aspects in material science and technology(Wang et al.,2007).Nanowires,nanotubes and nanoﬁbres of TiO2have been successfully prepared by electro-chemical synthesis,template based synthesis and a chemical based route although the effectiveness and practicality of some of these materials as photocatalysts are still being evaluated(Okour et al., 2009and Yu and Yu,2006).The discovery of the carbon nanotubes in the1990s by Iijima opened newﬁelds in the material science sector(Costa and Prado, 2009).Nanotubular materials are considered important in photo-catalysis owing to their special electronic and mechanical properties, high photocatalytic activity,large speciﬁc surface area and high pore volume(Idakiev et al.,2005and Yu and Yu,2006).Several studies have shown that titania nanotubes have better physical and chemical properties in photocatalysis compared with other forms of titanium dioxide.For example,titania nanotubes have a relatively higher interfacial charge transfer rate and surface area compared with the spherical TiO2particles(Colmenares et al.,2009).The transfer of the charge carriers along the length of titania nanotubes can reduce the recombination of positive hole and electron(Colmenares et al., 2009).Li et al.(2009)found that hollow titania nanotubes were highly efﬁcient in the photocatalytic decomposition of methyl orange compared with rutile phase TiO2nanopowders.Xu et al.(2006)stated that titania nanotubes were excellent photocatalysts,which were more reactive than TiO2nanopowder(anatase P25)in long cycles. Thus,titania nanotubes have raised expectations in what nanotech-nology can achieve because of their interesting microstructure and potential photoelectrochemical applications in dye-sensitized solar cells,gas sensors,organic light-emitting diodes and photocatalysts (Yu et al.,2007a).Considerable effort is now being devoted to the production of well-structured TiO2nanotubes with novel properties such as high surface area and pore volume(Idakiev et al.,2005).The approaches in developing TiO2nanotubes include chemical vapor deposition(CVD),anodic oxidation,seeded growth,the wet chemical(hydrothermal method and the sol gel method)(Guo et al., 2008;Morgan et al.,2008and Wang et al.,2007).Among these, hydrothermal method is often the method of choice because of its many advantages like cost-effectiveness,low energy consumption, mild reaction condition and simple equipment requirement(Guo et al.,2008).This method also allows for the manipulation of a large number of variable factors by which the morphology of TiO2 nanotubes that are produced is controlled.Photocatalysis is a“green”technology with promising applica-tions in a wide assortment of chemical and environmental tech-nologies(Colmenares et al.,2009).It has been singled out as a particularly attractive means by which to oxidize and remove toxic compounds,including carcinogenic chemicals,from industrial efﬂuent.The pollutants are chemically transformed and completely mineralized to harmless compounds such as carbon dioxide,water and salts(Gupta et al.,2006).C.L.Wong et al./Journal of Environmental Management92(2011)1669e1680 1670This process is an example of an advanced oxidation process (AOP),which is deﬁned as the chemical treatment process designed to produce strong hydroxyl radicals to oxidize and remove the organic and inorganic materials in the wastewater(Thiruvenkatachari et al., 2008).Photocatalysis is a chemical process that uses light to acti-vate a catalyst that alters the reaction rate without being involved itself.In heterogeneous photocatalysis,three main components are essential for photocatalytic reaction to take place:catalyst,light source and reactant(Thiruvenkatachari et al.,2008).Heterogeneous photocatalysis using titania nanotubes as pho-tocatalysts has recently gained importance in wastewater treat-ment.It has several advantages compared with other processes:(a) no mass transfer limitations,(b)complete mineralization of organic compounds to carbon dioxide,salts and water,(c)no addition of chemicals(d)no waste-solids disposal problems,(e)utilization of sunlight or near-UV light for irradiation and(f)only mild temper-ature and pressure conditions(atmospheric oxygen is used as oxidant)are necessary(Gogate and Pandit,2004;Konstantinou and Albanis,2004and Mahmoodi and Arami,2009).TiO2nanotubes have high cation-exchange ability that allows for large active catalyst loadings with high and uniform spreading. In the photocatalytic reaction,access to active sites is optimized by three main characteristics:high speciﬁc surface area,unavailability of micropores of reactants and open mesoporous morphology of TiO2nanotubes.The high performance of TiO2nanotubes in pho-tocatalysis is due to the semiconducting behavior of titania that produces a powerful electronic interaction between titania nano-tubes and their supports to increase the catalytic activity.As titania nanotubes are very resilient during heat treatment,their applica-tion as catalysts in photocatalysis is attractive.2.Fabrication of titania nanotubesThe fabrication of titania nanotubes is achieved by one of several methods:the surfactant-directed method,alumina templating synthesis,microwave irradiation,electrochemical synthesis and the hydrothermal method.Alumina templating synthesis has been a popular method to produce TiO2nanotubes over the last decades(Bavykin et al.,2006). TiO2nanotubes produced by template replication are uniform and well-aligned(Bavykin et al.,2006).However,this method is not suitable for the preparation of smaller nanotubes because of the limitation of the pore size of the mold prepared from porous alumina(Ma et al.,2006).TiO2nanotubes produced by the alumina templating method normally have large diameters(greater than 50nm)and the walls of TiO2nanotubes are composed of nano-particles(Costa and Prado,2009and Nawin et al.,2008).They are difﬁcult to split from their template components that are then destroyed and discarded,thus adding to operating cost(Bavykin et al.,2006and Nawin et al.,2008).TiO2nanotubes produced by the surfactant-directed method have smaller diameters and thinner walls as compared with products fabricated using the other methods(Ma et al.,2006).In addition, there are two main disadvantages of the surfactant-directed method: it is elaborate and time consuming to undertake(Ma et al.,2006).With the direct anodizaiton method,titania nanotubes are not split in an organized manner and the tubes do not have well-developed gaps in between(Bavykin et al.,2006).Besides,during the preparation of titania nanotubes,they have been immobilized on the surface of titanium effectively(Bavykin et al.,2006).Thus, they can be applied in different applications such as photocatalysis, hydrogen sensors,photoanodes for water splitting,and so on (Bavykin et al.,2006).The microwave irradiation method is another means by which TiO2nanotubes are synthesized.Wu et al.(Zhao et al.,2009)synthesized TiO2nanotubes by treating TiO2(anatase or rutile) with8e10M sodium hydroxide(NaOH)aqueous solution.On applying195W microwave power,TiO2nanotubes(8e12nm in diameter and100e1000nm in length,with multi-wall and open-ended structure)were produced.Notwithstanding the methods mentioned above,high quality of TiO2nanotubes with small diameters of about10nm are normally produced via a simple hydrothermal treatment of crystalline tita-nium dioxide nanoparticles with highly concentrated sodium hydroxide(Bavykin et al.,2006;Costa and Prado,2009and Nawin et al.,2008).Alkali titanate nanotubes are generated in hydro-thermal treatment where alkali ions are exchanged with photons to form the H-titanates.In order to produce TiO2nanotubes with different crystallographic phases such as anatase,rutile and broo-kite,thermal dehydration reactions in air are carried out at high temperatures.Kasuga et al.reported theﬁrst evidence for the production of small sized titania nanotubes through the hydrothermal process in the absence of molds for template and replication(Idakiev et al., 2005and Kasuga et al.,1998).The hydrothermal synthesis method is widely regarded as a convenient and inexpensive method to produce high quality TiO2nanotubes(Yu et al.,2006).In general,TiO2nanotubes show vast pore structure and high aspect ratio owing to their unique nanotubular structure(Yu et al.,2006). This renders the nanotubes attractive candidates for photocatalytic and photoelectrochemical systems.3.Hydrothermal method:formation mechanism of titania nanotubesThe fabrication of titania nanotubes by hydrothermal synthesis is performed by reacting titania nanopowders with an alkaline aqueous solution.While the hydrothermal method of titania nan-otube production has been comprehensively investigated in the past decade,the formation mechanisms,compositions,crystalline structures,thermal stabilities and post-treatment functions still remain areas of debate(Guo et al.,2007and Qamar et al.,2008).As a low temperature technology,hydrothermal synthesis is environmentally friendly in that the reaction takes place in aqueous solutions within a closed system,using water as the reaction medium(Sayilkan et al.,2006;Wang et al.,2008and Yu et al., 2007b).This technique is usually carried out in an autoclave (a steel pressure vessel)under controlled temperature and/or pressure.The operating temperature is held above the water boiling point to self-generate saturated vapor pressure(Chen and Mao,2007and Wang et al.,2008).The internal pressure gener-ated in the autoclave is governed by the operating temperature and the presence of aqueous solutions in the autoclave(Chen and Mao, 2007).TiO2nanotubes are obtained when TiO2powders are mixed with2.5e20M sodium hydroxide aqueous solution maintained at 20e110 C for20h in the autoclave(Chen and Mao,2007).The hydrothermal method is widely applied in titania nanotubes production because of its many advantages,such as high reactivity, low energy requirement,relatively non-polluting set-up and simple control of the aqueous solution(Lee et al.,2007).The reaction pathway is very sensitive to the experimental conditions,such as pH, temperature and hydrothermal treatment time,but the technique achieves a high yield of tinania nanotubes cheaply and in a relatively simpler manner under optimized conditions.There are three main reaction steps in hydrothermal method:(a)generation of the alka-line titanate nanotubes;(b)substitution of alkali ions with protons; and(c)heat dehydration reactions in air(Hafez,2009and Wang et al.,2008).The hydrothermal method is amenable to the prepa-ration of TiO2nanotubes with different crystallite phases such as the anatase,brookite,monoclinic and rutile phases(Wang et al.,2008).C.L.Wong et al./Journal of Environmental Management92(2011)1669e16801671Kasuga et al.(1998)carried out preliminary studies on titania nanotube formation using crystalline TiO 2nanoparticles as pre-cursors.The crystalline TiO 2nanoparticles were reacted with highly concentrated NaOH solution to form titania nanotubes by the hydrothermal ing this simple technique,titania nano-tubes were produced with uniform diameter (8e 10nm),speci ﬁc surface area (380e 400m 2/g)and length (50e 200nm)(Okour et al.,2009;Yu et al.,2007a ).Titania nanotubes produced in this manner were initially considered anatase phase products.When some of the Ti e O e Ti bonds were interrupted by the addition of NaOH solutions,some Ti þions were exchanged with Na þions to form Ti e O e Na bonds (Chen and Mao,2007).In this situation,the anatase phase existed in a metastable condition that had resulted from the “soft-chemical reaction ”at low temperature.The presence of Na þions in ﬂuenced the subsequent photocatalytic activity of the titania nanotubes (Sreekantan and Lai,2010).Kasuga and his workers subsequently introduced an acid washing treatment step following the hydrothermal process to form tri-titanate nanotubes (Kasuga et al.,1999).The purpose of the acid treatment was toremove the Na þions from the samples and to form new Ti e O e Ti bonds that would improve photocatalytic activity of the titania nanotubes (Kasuga et al.,1999).When the samples were treated with hydrochloric acid,the electrostatic repulsions disappeared immediately (Kasuga et al.,1999).The charged components were only gradually removed upon further washing with deionized water (Kasuga et al.,1999).The Na þions were displaced by H þions to form Ti e OH bonds in the washing process (Chen and Mao,2007).Next,the dehydration of Ti e OH bonds produced Ti e O e Ti bonds or Ti e O .H e O e Ti hydrogen bonds (Chen and Mao,2007and Kasuga et al.,1999).The bond distance between one Ti and another on the photocatalyst surface conse-quently decreased,facilitating the sheet folding process (Chen and Mao,2007and Kasuga et al.,1999).The electrostatic repulsion from Ti e O e Na bonds enabled a joint at the ends of the sheets to form the tube structure (Chen and Mao,2007and Kasuga et al.,1999).Kasuga et al.concluded that washing with acid and with deionized water were two principal crucial steps to produce high activity of titania nanotubes (Chen et al.,2002).The simple formation mechanism for titania nanotubes is shown in Fig.1.Yuan and Su (2004)proposed a mechanism for the fabrication of titanate nanotubes that was roughly similar to Kasuga ’s.They postulated that the crystalline structure of TiO 2was represented as TiO 6octahedral and that the crystalline structure of TiO 2shared vertices and edges to form in the three-dimensional structure.Ti e O e Ti bonds were broken by a cauterization process to produce the layered titanates.The titanate sheets were then peeled off intonanosheets and subsequently folded into nanotubes.The Na þions were exchanged and eliminated after washing with acid and then with deionized water.The major difference between Yuan and Su ’s titanate nanotubes and Kasuga ’s nanotubes was the dif ﬁculty in rolling up the former product completely.There were several tri-titanate layers produced simultaneously in the hydrothermal process to form three-dimensional nanosheets,resulting in the nanosheet edges being bent at the end of the hydrothermal process.Some researchers contend that the hydrothermal treatment is signi ﬁcantly the more important step as compared with the washing process in the mechanism of nanotubes formation.For eters and lengths of a few hundred nanometers by the hydro-thermal process using NaOH (10M)at 130 C,but without HCl washings.Wang et al.(Poudel et al.,2005)reported that the acid washing procedure was not necessary for the formation of titania nanotubes,essentially contradicting the assumptions of Kasuga et al.The foregoing notwithstanding,there are other researchers who are of the view that the acid washing practice is requisite for the titanate precursor sheets rolling into nanotubes (Liu et al.,2009).For instance,in 2007,Li and his workers (Liu et al.,2009)found that some partially curled nanofoils were formed after brie ﬂy washing with nitric acid and water.The nanofoils were transformed to nanotubes only after a more thorough washing with a large quantity of nitric acid and water (Liu et al.,2009).Yao et al.(Poudel et al.,2005)observed the formation of titania nanotubes after acid washing.Sun and Li (Poudel et al.,2005)observed that the washing step was the main step to the formation of both titania and sodium titanate nanotubes.There are also researchers who think that regardless of whether the titanate nanotubes are washed or unwashed,they are capable of removing organic or inorganic pollutants ef ﬁciently.Thus,Nawin et al.(2009)stated that the presence of Na had little bearing on the ef ﬁciency of the rate at which the pollutants decomposed,as this was in ﬂuenced more by the rate of nanotube sedimentation,available surface area and tubular structure.Wang et al.(2002)carried out an in-depth probe of the titania nanotube formation mechanism.They observed that the three-dimensional titanium dioxide structures (anatase phase),whichFig.1.Formation mechanism of TiO 2nanotubes using hydrothermal method (Chen and Mao,2007and Kasuga et al.,1999).C.L.Wong et al./Journal of Environmental Management 92(2011)1669e 16801672wereﬁrst reacted with sodium hydroxide aqueous solution,were transformed into2-dimensional layered structures.These lamellar structures then scrolled or wrapped to form titania nanotubes.In their opinion,the two-dimensional lamellar structure was essential in the formation of titania nanotubes.A formation of titania nanotubes was proposed by Wang et al. (Chen and Mao,2007).During the hydrothermal reaction with NaOH,the Ti e O e Ti bonds were broken.The free octahedral shapes shared edges between the Ti ions to form hydroxyl bridges,then, a zigzag structure was formed.Thus,the crystalline sheets rolled up in order to saturate these dangling bonds from the surface.This lowered the total energy and hence TiO2nanotubes were formed.There have been recent debates over the crystal structures of TiO2e based nanotubes,possible forms of which can be summa-rized as follows:(a)anatase/rutile/brookite TiO2,(b)lepidocro-cite H x Ti2Àx/4[]x/4O4(x w0.7,[]:vacancy),(c)H2Ti3O7/Na2Ti3O7/ Na x H2Àx Ti3O7and(d)H2Ti4O9(Guo et al.,2008;Ou and Lo,2007 and Qamar et al.,2008).Some researchers were of the opinion that anatase TiO2powder formed nanotubes more readily as compared with the rutile TiO2powder due to better surface energy of the former.In this connection,Wang et al.(Poudel et al.,2005) reported that the crystallinity of nanotubes was slightly better using the anatase TiO2phase as precursor.On the other hand,Chen et al.showed that nanotubes were obtained regardless of the size and the structure of the precursor or the starting materials(Papa et al.,2009).Ma et al.(Idakiev et al.,2005)contended that the nanotubes were formed from lepidocrocite H x Ti2Àx/4[]x/4O4(x w0.7,[]:vacancy) sheets rather than the other structures.When the duration of sonication was increased,the reactants formed rolled structures that transformed to rod-like structures.The growth of the length of rod-like structures was increased during the hydrothermal treatment. The sodium ions could then be washed off by the hydrochloric acid solution.Yoshikazu et al.(Poudel et al.,2005)reported that the nanotubes were hydrated hydrogen titanate(H2Ti3O7∙n H2O(n<3)).Du et al. (Poudel et al.,2005)found that the nanotube crystalline phase was not TiO2anatase but H2Ti3O7(a monoclinic system)and that the tubes had multi-wall morphology with interlayer spacing of 0.75e0.78nm.Kukovecz et al.(2005)tried to roll the tri-titanate nanosheets directly from the assumed Na2Ti3O7intermediate in their experiment.However,since sodium tri-titanate was quite stable under the reaction conditions(10M NaOH,130 C),it was not destroyed by NaOH,and nanotube formation did not occur.With the same alkaline hydrothermal treatment,the researchers then used the assumed Na2Ti3O7intermediates as seeding materials to convert anatase TiO2into titania nanotubes.In this instance,the yield of titania nanotubes was almost100%.Fluctuation in the local concentrations of the intermediates might have initiated the formation of nanoloops from the anatase starting materials,and these served as the seeds for titania nanotube formation.Peng et al.(Idakiev et al.,2005and Ou and Lo,2007)were of the view that H2Ti3O7was produced in the hydrothermal treatment. They proposed the two most likely mechanisms in tri-titanate nanotubes formation.In the initial stage of the hydrothermal process,the reaction between titanium dioxide and concentrated sodium hydroxide solution produced a highly disordered inter-mediate,which contained Ti,O and Na.In theﬁrst proposed mechanism,single sheets of the tri-titanate(Ti3O7)2Àstarted to grow at a slow rate within the disordered intermediate phase.The slow growth was mainly due to the high concentration of NaOH that was present.As the tri-titanite sheets grew two-dimensionally, they rolled up into nanotubes.In the process,however,some H2Ti3O7plates failed to wrap up successfully,resulting in the edges of H2Ti3O7plates having a tendency to twist.In the second proposed mechanism,the lepidocrocite Na2Ti3O7was postulated to assume the form of disorder-phase nanocrystals that was not stable in the boiling water.With the excessive of Naþcations intercalating in the interlayer spaces,single layers of tri-titanate were either ﬂaked off to form nanocrystals or they were curled like wood shavings into nanotubes.Yang et al.(Idakiev et al.,2005and Ou and Lo,2007)stated that titanium dioxide particle swelling was indicative of Na2Ti2O4(OH)2 formation.After the addition of concentrated NaOH solution,the shorter Ti e O bonds split and swelled.The linear portions(one-dimensional)connected to each other in the presence of OÀe Naþe OÀbonds to produce planar fragments(two-dimensional).Titania nanotubes would then be formed by the formation of covalent bonds within the end groups.Seo et al.(2009)studied the formation mechanism of titania nanotubes by the hydrothermal process at a higher temperature of 230 C TiO2wasﬁrstly reacted with NaOH solution to form Na2Ti2O5$H2O.Next,the hydrochloric acid washing step was carried out to remove Naþions and to form the exfoliated sheets that then curled up to produce more uniform nanotube structures.At the present time,the formation mechanism is still ambiguous despite efforts that have been made to come up with an acceptable and veriﬁable explanation(Bavykin et al.,2006and Ribbens et al., 2008).Even though a complete understanding has yet to be ach-ieved,it is generally accepted that titanium dioxide(amorphous, anatase,brookite and rutile)under alkaline circumstances are converted to intermediates(single layer and multi-layered titanate nanosheets)that roll or curl into nanotubular structure(Bavykin et al.,2006).The putative driving force that is responsible for the rolling or curving nanotubular structure has been suggested by some groups(Bavykin et al.,2006).Table1shows the major steps of titania nanotube formation proposed by various researchers.4.Factors inﬂuencing the formation of titania nanotubesThere are several considerations affecting the formation of titania nanotubes(Fig.2).These include(a)the starting materials (commercial,self-prepared,amorphous,crystalline,anatase,rutile and brookite),(b)sonication pretreatment,(c)hydrothermal temperature,(d)treatment time and(e)post-treatments(washing, calcinations)(Morgan et al.,2008and Wang et al.,2008).The characteristics and morphology of titania nanotubes such as the speciﬁc surface area,crystal structure and others are dependent on the hydrothermal conditions selected.4.1.Effect of the starting materialsThe hydrothermal synthesis of titania nanotubes can start with different titania powders such as rutile or anatase TiO2,Degussa TiO2(P25)nanoparticles,layered titanate Na2Ti3O7,Ti metal, TiOSO4,molecular Ti IV alkoxide,doped anatase TiO2,or SiO2e TiO2 mixture(Wang et al.,2008).Alternatively,titania sol can also be utilized as the starting reactant in the hydrothermal process.It has been observed that the structural properties of the nanostructured TiO2products are markedly dependent on different starting TiO2 materials.Basically,nanotubes with outer diameters between10 and20nm can be obtained by the hydrothermal method when starting with titania powder of relative large particle size,such as rutile TiO2,Degussa TiO2(P25),and SiO2e TiO2mixture(Wang et al., 2008).Saponjic et al.(2005)used different starting materials to produce titania nanotubes using hydrothermal method,which are Degussa TiO2P25nanoparticles,TiO2colloids,and molecular Ti IV alkoxide.Titania nanotubes obtained from those starting materialsC.L.Wong et al./Journal of Environmental Management92(2011)1669e16801673。

Bringing_Cutting-edge_Life_Science_Technology_to_C

I t is already something to be proudof that a domestic pharmaceuticalindustry group focusing on lifesciences owns one piece of world-class cutting-edge technology in this field. However, the Canada North-ernPharm Group has a total of nine: research and development on anti-cancer drugs and new drugs combating neurological diseases, new technology for generic drugs, APIs and intermedi-ates, high-end natural health products, 3D medical printing, early stage cancer tests, autologous stem cell expansion and differentiation technology, bio-sen-sors for testing gastrointestinal diseases, and lifetime healthcare plans.Dr. Pang Jun, the chairman of the Group, is a famous scientist in the field of life science and is very familiar with the company’s cutting-edge technolo-gies. His top science and engineeringeducation in Canada and China andhis role as a research leader in the fieldof life science for many years has madehim a calm and practical man. Thecompany has gradually grown from adrug research and development labora-tory with a mere five people when itwas established in 2009 into a largediversified group company. He said thataround the end of this year, the companywill be listed on Nasdaq with a marketvalue of nearly one billion US dollars.The local media in Canada honoredhim as “a model for Chinese business-men in North America and the pride ofChinese-Canadian businessmen.”It was always his wish and goalto win glory and benefit the health ofChinese people. Today, the Group hassuccessively established subsidiariesin China and will invest RMB 7 bil-lion in research and development inthe next five years, with the purposeof granting China access to the mostcutting-edge medical technology.Steering in the right directionand building a world-class teamIn 2009, the company was just alaboratory consisting of only five sci-entists; in 2010, a drug R&D labora-tory was built where drug moleculardesign, synthesis, and characterizationcould be conducted; in 2011, a teamsof scientists consisting of doctorsand postdoctoral researchers fromrenowned universities in the UnitedStates and Canada was built; in 2012,Introducing the company’s research and development in life scienceand technology to the professors from MIT and Harvard University.Bringing Cutting-edge Life Science Technology to China— Interview with Dr. Pang Jun, Chairman of Canada NorthernPharm Group4849demic papers in the most authoritative magazines in the field, including Nature, Cell, and Cancer Research. It is such tal-ent that makes up the company’s R&D team, which ranks top in the world. Sup-ported by this team of talented scholars from different backgrounds around the world, NorthernPharm Group has a keen insight into the chemical and bio-pharmaceutical industries in order to stay strong and competitive in the market. “As a result, our products can stand out from others,” said Dr. Pang.“T o unite talents, the leader himself must be at the forefront of technology,” said Dr. Pang. After graduating from the Chinese Academy of Sciences with a PhD degree in organic chemistry, he continued his postdoctoral research at Queen’s University in Canada. He has received honors such as the Chinese Academy of Sciences President’s Schol-arship, the American Exxon Chemistry Scholarship, and the title of outstanding alumni of the Dalian Institute of Chem-ical Physics, the Chinese Academy of Sciences. Later, he worked in the Cancer Institute affiliated with the National In-stitute of Health to study new anticancer drugs. He has served as co-chair of the Major Diseases and New Drug Creation Conference of International Medicines R&D Committee, and the guest edi-tor of a special issue of the International Academic Journal about cancer. Havingthe products began selling to 15 coun-tries and regions around the globe; in 2015, breakthroughs were made in the company’s two new anti-cancer drugs and a new neurological drug which were developed and researched by themselves; and finally, in 2018, the company will be listed on Nasdaq.In terms of scientific research results, the company’s two new anti-cancer drugs have been biologically tested; a new drug for the treatment of Alzheimer’s disease has already under-gone mouse experiments; several major breakthroughs have been achieved in new generic drug technology, with an average of five to ten challenging tech-nologies being developed every year; more than 300 new pharmaceutical intermediates are designed and synthe-sized every year; andits pharmaceutical intermediates have been continuously been in the top three among a dozen similar companies in Canada and in the top ten in both Canada and the US.Based on advanced life science technologies, the Group has trans-formed scientific and technological achievements into the impetus driving the company. The Group gives priority to independent research and develop-ment, and at the same time also coop-erates with world-renowned universi-ties, such as Harvard University, the Massachusetts Institute of Technology (MIT), the University of California in San Diego, the University of Toronto, Queen’s University, the University of Waterloo, McMaster University, and the Chinese Academy of Sciences, in order to develop new drugs and new medical technology.What made the initial five-person drug R&D lab evolve into today’s large diversified group ? During the inter-view, Dr. Pang explained that, in order to achieve rapid progress, the company should steer themselves in the right di-rection, select a world-class team, focus on the world’s leading technology, and seek global cooperation. When it comes to how to choose and unite talents, he said: “Only by attracting high-level tal-ent can the subsequent technological breakthroughs be made.” These technical elites have received a world-class educa-tion, researched in leading laboratories, and published many high-quality aca-been engaged in research on drug devel-opment and in the biomedical field, Dr. Pang has published 38 papers, owns and applied for 15 patents, and possesses 68 proprietary technologies. It is based on his distinguished achievements in sci-entific research and his solid accumula-tion of honors from top universities and research institutions in China, the US and Canada, that such a world-class core R&D team can be built.“In addition to attracting outstand-ing scientific research professionals, it is also crucial to decide the company’s development direction.” He went on to explain that the company’s nine orienta-tions since its establishment are: new drugs, generic drugs, APIs and interme-diates, health products, stem cells, early stage cancer tests, 3D bioprinting, bio-sensors for testing for gastrointestinal diseases and lifetime healthcare plans. A good direction means forward-facing judgment of the future. “For example, 3D printing, early stage cancer tests, and stem cells are all the directions which we chose more than ten years ago, and they have now been proven to be correct choices,” Dr. Pang said.Providing the most cutting-edge medical technology achievement for the Chinese peopleAccording to Dr. Pang’s intro-duction, Canada NorthernPharm Group has established Sino-Canadian International Life Science Technology Co., Ltd. in Shenzhen and Shanghai, etc. In addition, Jiahuayaokang Phar-maceutical Co., Ltd., a holding sub-sidiary of the Group, was established in Shenzhen. This company was estab-lished in 2015 and focuses on the re-search and development of new drugs, generic drugs and health products. Its development goal is to become one of the top three pharmaceutical compa-nies in China. Currently, the company is developing rapidly and will be listed in Hong Kong around 2021.Regarding the general situation of the Group’s current business in China, Dr. Pang mentioned that they have signed contracts with more than 110 Chinese pharmaceutical companies (part-ners). These cooperative projects include research into both new drugs and genericdrugs as Dr. Pang hopes to achieve thegoal of entering the top three in terms of technology for anticancer drugs and new drugs for the nervous system (treating Alzheimer’s disease). In addition, the co-operation also includes 3D medical print-ing and natural products, among which the healthcare products developed and made by the company will also be on the market in China this September.As domestic consumers prefer health products from Australia and Europe,what are the advantages of their own health products? Dr. Pang said that all the health products they sell in China will be researched and manufactured in Canada. “Each raw material is systematically researched by our scientist team, and the products are strictly selection from the origin of raw materials to the nutritional value.”After years of effort, Canada NorthernPharm Group has established a sound natural product supply chain to ensure pollution-free and high-quality products. For example, they went around the world to find the best ginseng as a raw material before finally settling on-natural American ginseng from Canada. The ginseng will be cultivated for five years to guarantee that they can achieve the highest quality. With regards to the selection of deep-sea fish from which to extract oil, they chose fish rich in unsaturated fatty acids grown in the opaque zone. After purification in their laboratories, the effective ingredients forthe oil, DHA and EPA are more than90%. In another example, when select-ing the raw materials for active calcium,they discovered from cartilage in deep-sea shark fins that only shark cartilagewith a large aperture can be completelyabsorbed by the human body. They de-veloped a unique formula that combinesshark cartilage and high-purity MSMwith vitamin D to achieve the best re-sults in both enhancing bone density andpromoting cartilage tissue growth. Inorder to find natural antibiotics with thebest effects, they again searched globallyand finally decided on the Jiangxi hon-eysuckle planting base, which is one ofthe places with the best ecological envi-ronments in China. Its red land which isfull of rich minerals can be used to culti-vate honeysuckle of the highest quality.Through research, the company’s scien-tists found thatchlorogenic acid, i.e.theactive ingredient of the honeysuckle inthis place, exceeds the average standardof the one prescribed in Chinese Phar-macopoeia.The pride of Chinese-CanadianbusinessmenThrough nearly ten years of hardwork, the NorthernPharm Group haswon the attention and praise of the en-tire industry in Canada by its continu-ous record-breaking achievements andself-transcendence.The government of the city ofNiagara Falls, where the company islocated, put the Group on the coverof a paper listing important economicdevelopment in 2015 and provideda full-page introduction of the com-pany on page 5 of the paper. The mainnewspaper in this region, the NiagaraFalls Review, published an exclusiveinterview with Dr. Pang on March 12,2016. On March 11, 2017, the Groupwon the 2017 award for the Best Chi-nese Company in Canada. In Septem-ber 2017, the Group won the honorarytitle of “2017 Top Ten Most HonestChinese Enterprises in the World”.Dr. Pang has been devoted toimproving the position of Chinesebusinessmen in Canada and othercountries. The Group is setting up theNiagara International Medical Centerin Canada, and Dr. Pang is becomingthe “Number one Chinese person in thepharmaceutical industry”. As the prideof Chinese-Canadian businessmen,Dr. Pang has strong emotions towardsChina, perhaps because he went aboardafter finishing his doctorate programin China. He continued that when hewent to Canada to continue his studies,he wanted to learn the most advancedtechnology in the world and to benefitthe health of human beings. A Chineseflag has been flown outside the com-pany building since its establishment.Dr. Pang has always fulfilled hispromises, from completing his studiesto establishing a company and con-ducting business in China, and he isundertaking more responsibilities torepay society as his own company isbecoming more strong and powerful.For example, the Group sponsoredmany activities and associations, in-cluding: the “2017 NorthernPharm-SD Group Panda Cup InternationalTable Tennis Tournament”, theChinese-Canadian Cultural Relicsand Art Research Foundation, theInternational Youth Culture and ArtsFestival, the 101st Annual Chemis-try Conference of Canada, the 2018Canada Annual Pharmacy Confer-ence, the International ChemistryConference in Queen’s University, andthe Bethune Medical DevelopmentAssociation of Canada.Dr. Pang shared informations and talked about cooperation issues at University of Toronto.5051As the guest of honor to attend the prize presentation ceremony of the Canadian Bethune Medical Development Association.。

液相合成纳米二氧化钛

Review /CR
Solution-Phase Synthesis of Titanium Dioxide Nanoparticles and Nanocrystals
Matteo Cargnello,† Thomas R. Gordon,† and Christopher B. Murray*,†,‡
© XXXX American Chemical Society
Special Issue: 2014 Titanium Dioxide Nanomaterials Received: March 27, 2014
A
/10.1021/cr500170p | Chem. Rev. XXXX, XXX, XXX−XXX
†
Department of Chemistry and ‡Department of Materials Science and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States as high thermal and chemical stability, make it one of the most employed materials in pigments, UV sunscreens, cosmetics, medical implants, and sensors.1 In addition to these traditional applications, titania is being employed in many other emerging applications including optoelectronics, photovoltaics, catalysis, fuel cells, batteries, smart windows, and self-cleaning and antifogging surfaces. It is also the most heavily investigated wide band gap semiconductor for photocatalytic and photoCONTENTS electrocatalytic processes, which have gained increased interest 1. Introduction A in recent years within the scientiﬁc community.2 2. General Principles for Synthesis of Titania Titania particles and structures possessing small particle and Particles D feature size (below 100 nm) can show high visible light 2.1. Solution-Phase Synthesis of Uniform Partransparency combined with high UV light absorption, and in ticles D some cases they display iridescence.3 Small nanoparticles can 2.2. Surfactants and Protecting Ligands E also enhance the adsorption coeﬃcients of organic molecules 3. Titanium Precursors F adsorbed on their surfaces.4 In addition, altering the size, as well 3.1. Titanium Alkoxides F as the shape, of titania nanoparticles has been shown to 3.2. Titanium Halides (TiCl4 and TiF4) F strongly inﬂuence the adsorption of molecules and the rate of 3.3. Titanatranes G electron transfer events at the particle surface, which has 3.4. Titanium Metal and Carboxylate-Derived potentially important implications for a variety of applications, Compounds G including catalysis. As a result, titania particles in the size 3.5. Titanium(IV) Bis(ammoniumlactato) Dihydrregime 1−100 nm are very interesting for a variety of oxide G technological applications, and the synthesis of well-controlled 3.6. Titanium Sulfate and Oxysulfate G titania nanostructures is important in order to impart the 3.7. Oxobis(2,4-pentanedionato-O,O ′)titanium desired characteristics to the ﬁnal material. Particle size, shape, [TiO(acac)2] G and phase are critical in determining the ﬁnal properties of the 4. Aqueous Methods G nanoscale materials. 4.1. Sol−Gel Methods G Among the many methods used to prepare nanoparticles and 4.2. Hydrothermal Methods J nanostructures, a primary classiﬁcation can be made by 5. Nonaqueous Methods O distinguishing physical and chemical methods. Physical 5.1. Solvothermal Methods O methods usually rely on top-down approaches in which small 5.2. Nonhydrolytic Methods R structures are fabricated from larger ones. In contrast, chemical 6. Templated Approaches U methods most commonly proceed through a bottom-up 6.1. Soft Templates V approach, in which molecular precursors react to form the 6.2. Hard Templates W ﬁnal larger structures. Both methods have advantages and 7. Summary and Perspectives W disadvantages: physical methods can produce large quantities of Author Information X material (e.g., the preferred methods in the electronic industry Corresponding Author X are physical methods) but their resolution is limited to tens of Notes X nanometers. Chemical methods, on the other hand, are Biographies X typically performed at a smaller scale in which the precision Acknowledgments X during the preparation of small (e.g., <100 nm and often <10 References X nm) structures can approach the atomic-layer limit.5 Wet chemical or solution-phase methods, in particular, are best suited to achieve the ﬁnest control over particle size, shape, and composition as desired for several of the above-mentioned 1. INTRODUCTION Titanium dioxide or titania (TiO2) is one of the most abundant compounds on our planet and a very appealing material for a variety of applications. Unique physical and chemical characteristics combined with earth abundance and nontoxicity, as well

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1. INTRODUCTION Graphene, the two-dimensional sp2-hybridized carbon, is currently, without any doubt, the most intensively studied material. This single-atom-thick sheet of carbon atoms arrayed in a honeycomb pattern is the world’s thinnest, strongest, and stiﬀest material, as well as being an excellent conductor of both heat and electricity. It is no wonder that this two-dimensional material is considered, from the application viewpoint, to be even more promising than other nanostructured carbon allotropes, that is, 1-dimensional nanotubes and 0-dimensional fullerenes. Since the ﬁrst experimental evidence of the electronic properties of graphene in 2004,1 a major focus of experimental research has been concentrated on the development of new synthetic routes enabling an eﬀective production of well-deﬁned sheets.2−18 The commonly applied methods include the micromechanical1 or chemical exfoliation of graphite,13 chemical

Currents in the Compressible and Incompressible Regions of the 2DEG

a r X i v :c o n d -m a t /9409004v 1 1 S e p 1994Currents in the compressible and incompressible regionsof the two-dimensional electron gasMichael R.Geller and Giovanni VignaleDepartment of PhysicsUniversity of MissouriColumbia,Missouri 65211We derive a general expression for the low-temperature current distribution ina two-dimensional electron gas,subjected to a perpendicular magnetic ﬁeld and in a conﬁning potential that varies slowly on the scale of the magnetic length ℓ.The analysis is based on a self-consistent one-electron description,such as the Hartree or standard Kohn-Sham equations.Our expression,which correctly describes the current distribution on scales larger than ℓ,has two components:One is an “edge current”which is proportional to the local density gradient and the other is a “bulk current”which is proportional to the gradient of the conﬁning potential.The direction of these currents generally display a striking alternating pattern.In a compressible region at the edge of the n th Landau level,the magnitude of the edge current is simply j =−eωc ℓ2(n +12)eωc /2π,whereas in an incompressible strip with integral ﬁllingfactor νit is νeωc /2πwith the opposite sign.PACS numbers:73.20.Dx,73.40.–c,73.40.Hm,73.50.–hI.INTRODUCTIONIn the past several years,there has been tremendous interest in the low-temperature properties of a two-dimensional(2D)electron gas in a strong magneticﬁeld.The most common experimental realization of this system is at a modulation-doped semiconductor heterojunction,grown by molecular beam epitaxy.One important question,now receiving much attention,is the distribution of current when the system is subjected to a conﬁning potential,or to an applied voltage,or to both.Knowledge of the equilibrium and nonequi-librium current distributions is important for understanding the quantum Hall eﬀect,the electronic properties of low-dimensional semiconductor nanostructures such as quantum dots or quantum wires in the presence of a magneticﬁeld,and for understanding meso-scopic transport in general.The current distribution can also be used to calculate the magnetic properties(for example,the orbital magnetization)of a conﬁned2D electron gas.Two types of methods are commonly used to obtain a conﬁned2D electron gas.Litho-graphic methods result in the well-known etched structures consisting of a patterned region of the2D electron gas along with its compensating positively charged donors.The second method produces a conﬁning potential via one or more evaporated metal gates.In both cases,the actual conﬁning potential is the sum of the potential from the remote donors and gates,plus the self-consistent electrostatic potential(and possibly the exchange-correlation scalar potential)of the electrons.Typical electron sheet densities in the modulation-doped 2D electron gas vary from1011to1012cm−2.The most interesting eﬀects of an applied magneticﬁeld then occur atﬁeld strengths ranging from1to10Tesla,where only a few Landau levels are occupied.At these highﬁeld strengths,the magnetic length,ranging from50to a few hundred˚A,is small compared with the length scale over which the con-ﬁning potential changes by¯hωc,whereωc is the cyclotron frequency.In this sense,theconﬁning potential is slowly varying.Vignale and Skudlarski1have recently used current-density functional theory2to derive an exact formal relation between the ground-state current and density distributions of a three-dimensional interacting electron gas in the presence of a magneticﬁeld.In the local density approximation(LDA),valid when the density varies slowly on the scale of the magnetic length,they obtain an explicit formula for the current in terms of the density gradient with a coeﬃcient of proportionality involving thermodynamic quantities for a uniform electron gas.However,the application of this LDA result to the2D electron gas is complicated by the presence of incompressible regions,where the density gradient vanishes and the coeﬃcient diverges.Furthermore,in the2D electron gas,the density may change from one integralﬁlling factor to another over a single magnetic length,invalidating the a priori application of the LDA.This has motivated us to reexamine the relation between current and density in two dimensions,without using the LDA.Another motivation for this work is to study the equilibrium currents in edge channels.3−7 In a recent paper,Chklovskii et al.5have calculated the classical electrostatic potential and density of a gate-conﬁned2D electron gas.They show that the electrostatic potential consists of a series of wide steps of height¯hωc.In contrast to a naive single-electron picture, there are wide compressible regions where the density gradually changes from one integral ﬁlling factor to another,the so-called edge channels,and narrow incompressible regions of integralﬁlling factor.This type of bahavior had been previously noted by McEuen et al.6in the context of quantum dots.The classical electrostatic analysis of Chklovskii et al.has also been extended to narrow gate-conﬁned channels7and to quantum dots.8 The electrostatics of edge channels in mesa-etched samples has been studied by Gelfand and Halperin,9and considerable eﬀort has been recently devoted to extending the classical electrostatic treatment to self-consistent Hartree and Hartree-Fock approximations.9−13A related question is the transition between sharp and smooth density distributions as theslope of the conﬁning potential is changed.13,14Prior to the recent work on edge channels,considerable progress had already been made in understanding the distribution of current in the quantum Hall regime.In one of the early papers on this subject,MacDonald et al.15used the localized nature of the Landau states to show that the ground-state current density,directed in the y direction along a Hall bar whose conﬁning potential V(x)varies in the x direction only,is simply proportional to V′(x)in the interior of the Hall bar.Several authors15−20have calcu-lated nonequilibrium density and current distributions in particular conﬁning potentials, and the correct description of the nonequilibrium steady state is now a problem of great interest.18−23In particular,Thouless has emphasized the importance of nonequilibrium bulk currents that are induced by edge-charge redistribution.20In this paper,we derive the low-temperature(k B T<<¯hωc)density and current dis-tributions for a high-mobility spin-polarized2D electron gas in an arbitrary conﬁning po-tential V(r)and uniform magneticﬁeld B=B e z,assuming only that the potential varies slowly on the scale of the magnetic lengthℓ≡(¯h c/eB)1)∇ρn(r)×e z(1.1)2andej bulk≡−Hereωc≡eB/mc is the cyclotron frequency.The electron number density,ρ,is given byρ=12)+V(r)−µ ,(1.3)whereµis the chemical potential,f(ǫ)≡ eǫ/k B T+1 −1is the Fermi distribution function, andρn is simply the n th term in(1.3).At low temperatures,the electron density is uniform everywhere except near a number of edges,where the density changes by an amount (2πℓ2)−1.These compressible regions,or edge channels,follow lines of constant conﬁning potential.The edge current(1.1)is a sum of nonoverlapping parts;the contribution from the edge of the n th Landau level is j edge=−eωcℓ2(n+1νisνeωc/2π,independent of the strip position,geometry,and width.Similarly,the mag-nitude of the integrated current in an ideal edge channel at the edge of the n th Landau level is found to be(n+1II.EQUILIBRIUM CURRENT DISTRIBUTIONWe shallﬁrst obtain the single-particle Green’s function for the conﬁned electron gas by the following method:(i)First,a Dyson equation is obtained for the Green’s function G of the conﬁned electron gas,in terms of the Green’s function G0of the uniform electron gas and the conﬁning potential V(r);(ii)Then the short-ranged nature of G0is used to separate the potential near r into a local constant potential,V(¯r),and a gradient,(r−¯r)·∇V(¯r), for some¯r near r;(iii)Next,the local constant potential terms are summed to all orders, resulting in a Green’s function G1;(iv)The gradient terms are then treated toﬁrst order, resulting in aﬁrst order gradient expansion for G;(v)Finally,the local direction of the potential gradient is used toﬁnd a gauge in which the Green’s function takes a particularly simple form,corresponding to an expansion in eigenstates that are localized in the∇V(¯r) direction.As stated above,we consider a2D electron gas in a uniform magneticﬁeld B=B e z and in a slowly varying potential V(r),where r=(x,y).We assume that the electrons are spin-polarized by the strong magneticﬁeld,and we disregard the resulting constant Zeeman energy.The Hamiltonian may be written asH=H0+V,(2.1) where H0≡1c A 2is the Hamiltonian for an electron in the presence of the magnetic ﬁeld alone.In terms of the exact normalized eigenstatesΨαand eigenvalues Eαof H,the Green’s function for the conﬁned electron gas may be written asG(r,r′,s)= αΨα(r)Ψ∗α(r′)f[s−µ]G(r,r,s),(2.3)2πiand current density,j(r)=−e2πif[s−µ]limr′→rRe −i¯h∇+es−¯hωc(n+12)φnq.(2.6)In the gauge A=Bx e y these eigenstates areφnq=C n e−iqy e−1ℓ−qℓ)2H n x2ℓ −1 4|r−r′|2/ℓ2,except at its poles.ThenG(r,r′,s)=G0(r,r′,s)+ d2r′′G0(r,r′′,s) V(¯r)+(r′′−¯r)·∇V(¯r) G(r′′,r′,s),(2.9) where¯r is any point near r,and where higher order gradient terms have been neglected. Equation(2.9)is now solved iteratively,keeping all terms containing no gradients and all terms containing one local gradient.This leads toG(r,r′,s)=G1(r,r′,s)+ d2r′′G1(r,r′′,s)(r′′−¯r)·∇V(¯r)G1(r′′,r′,s),(2.10)where G1(r,r′,s)satisﬁesG1(r,r′,s)=G0(r,r′,s)+V(¯r) d2r′′G0(r,r′′,s)G1(r′′,r′,s).(2.11) For notational simplicity,the dependence of G1on¯r has been suppressed.The solution of the integral equation(2.11)isG1 r,r′,s =G0 r,r′,s−V(¯r) ,(2.12) valid for any¯r near r.The Green’s function G0,when renormalized by the local potential V(¯r),simply has its energy argument shifted by V(¯r).Because of the arbitrariness in the choice of¯r,G1is not unique.However,the eﬀect of a change of¯r on G1is compensated for by the corresponding change in the second term in(2.10),and the complete Green’s function(2.10)is independent of¯r toﬁrst order in the local gradient∇V(¯r).At this point we have obtained a gradient expansion for the Green’s function G.Un-fortunately,the expression(2.10)contains all matrix elements nq|r|n′q′ of r in the basis (2.7).To circumvent this,we shall perform a gauge transformation,for each¯r,which rotates the direction of the vector potential so that it is perpendicular to the local gradient of the conﬁning potential.The gauge-transformed Green’s functions may then be written in terms of eigenfunctions which are localized in the∇V(¯r)direction,resulting in a simple closed-form expression for G.To this end,we shall use the slowly varying function V(r)to deﬁne a local orthonormal basis n a(a=1,2)on the z=0plane:∇V(r)n1(r)≡ﬁxed¯r,and hence directed perpendicular to∇V(¯r),is given byA′≡B[n1(¯r)·r]n2(¯r).(2.14)We suppress the parametric dependence of A′on¯r.This vector potential describes a uniform magneticﬁeld(∇×A′=B)and is transverse(∇·A′=0).The normalized eigenstates of H0in this gauge areψnq(r)=C n e−iqηℓe−1¯h c [Λ(r)−Λ(r′)]GA′(r,r′,s).(2.16)This allows one to compute a given matrix element(r and r′regarded as matrix indices) of G A by transforming to some gauge A′where G A′is simpler.One may choose a diﬀerent gauge for each matrix element.The generator of the gauge transformation from A=Bx e y to A′is given by∇Λ(r)=B[n1(¯r)·r]n2(¯r)−Bx e y.(2.17) Then we obtainG A(r,r′,s)=e ies−¯hωc(n+1[s−¯hωc(n+12)−V(¯r)],(2.18)whereΛis given by(2.17).The matrix elements nq|r|n′q′ are now in the basis(2.15).Because∇V(¯r)points in the n1(¯r)direction,only the matrix elements of n1·r are required.In what follows,we shall always choose¯r=r;the symmetric choice¯r=12πℓ2 n f ¯hωc(n+1m ds c n1·A G(r,r′,s).(2.21)Using(2.18)leads toj1=−eωcℓ2e2πif[s−µ]Re −emcBx n2·e yρ.(2.23)A straightforward calculation leads toj2=−e2ωcℓ22)|∇ρn|+eωcℓ2|∇V|2)+V(r)−µ .Finally,after using(2.17),weﬁndj2=−eωcℓ2 n(n+1¯hωcρ.(2.25) Note that∇ρis antiparallel to∇V.Therefore,the equilibrium current density is given by the expression stated in Section I.PARISON WITH AN EXACTLY SOLVABLE CASEIn this section,we compare our results to the exact equilibrium density and current distributions of a noninteracting2D electron gas in a uniform magneticﬁeld B=B e z and a parabolic conﬁning potentialV(x)=12L)−12(xΩkL)2Hn xΩkL (3.2)E nk=¯hΩ(n+12)+V(kL2)−µ]|Ψnk|2,(3.4) whereµis the chemical ing(3.2),this may be written asρ=1ω2cn 2n n!π12)+Ω2L−K)2H2n xwell.The curvature of the conﬁning potential is chosen to be ω0=14ω2c ℓ.(3.6)Hence,the actual density proﬁle is slightly contracted relative to the proﬁle given by (1.3).The exact equilibrium current density,which is directed in the y direction,may be written asj = n ∞−∞dk f [¯h Ω(n +1m Re Ψ∗nk −i ¯h ∂c A ·e y Ψnk (3.8)is the contribution to the current density from the state Ψnk .From (3.2),we obtainj nk =eωc kℓ2−x |Ψnk |2,which may be rewritten asj nk =eL Ω2L |Ψnk |2+eωc ℓ2 V ′(x )edge current,where the bulk contribution is exactlyj bulk=eωcℓ2 V′(x)2πℓ 1+ω204 n(2n n!π12)+Ω2L e−(K−x L .(3.11)In Fig.2we compare the exact ground-state current distribution(dashed curve)to the current distribution given in Section I(solid curve).The bulk contributions to the current density are nearly identical;they diﬀer only in that the density in(1.2)and the exact density in(3.10)are slightly diﬀerent,as shown in Fig.1.The sharp steps inρlead to the sharp zig-zag structure in the solid curve of Fig.2.However,we see that the approximate edge current(1.1),which at zero temperature consists of a series ofδ-functions,does not capture the form present in the exact edge current(3.11).However,as we shall show, the edge current(1.1)correctly accounts for the net current associated with a given edge (the integrated edge current density),in accordance with the earlier assertion that our distributions correctly describe the large-scale features of the exact distributions.To prove this,we deﬁne the integrated edge currents,I+n and I−n,associated with the two edges of the n th Landau level,one edge located to the right(+)of the origin and the other located to the left(−).I+n is deﬁned byI+n≡eωcω2c72)−1 ∞dx ∞−∞dK f[¯hΩ(n+1ω2c V KL −µ]× K−x L)2H2n K−xof each Landau level are of equal magnitude and are opposite in sign,as is well-known.In Appendix I,we show that the integrated ground-state edge currents are equal toI±n=∓ n+12π 1+ω202.(3.13) This result is also valid for low temperatures such that k B T<<¯hωc.The integrated edge currents given by the distribution(1.1)are easily shown to beI±n=∓ n+12π,(3.14) which is equal to(3.13),apart from small corrections of orderω20/ω2c.Fig.2also demonstrates that the direction of the current oscillates with position. This striking feature is correctly accounted for in our general expression by noting that ∇ρis antiparallel to∇V.These oscillations,which originate from the oscillations in the magnetization of the2D electron gas as a function ofﬁlling factor,are a generic feature of the current distribution in a conﬁned2D electron gas.This is explained further in Appendix II.IV.APPLICATIONSA.Current distribution in a Hall barThe general expression we have derived for the low-temperature current distribution in a2D electron gas can be easily used with a self-consistent potential obtained by solving the Hartree,Hartree-Fock,or Kohn-Sham equations.We now apply our result to a stepped potential characteristic of the low-temperature self-consistent Hartree potential of a narrow gate-conﬁned Hall bar.The Hall bar is assumed to lie along the y direction,with a conﬁning potential V(x)and chemical potential as shown in Fig. 3.A uniform magneticﬁeld is applied in the z direction.The conﬁning potential we use is similar to that obtained classically by Chklovskii et al.6for a narrow gate-conﬁned channel,and conﬁrmed by self-consistent Hartree and Hartree-Fock calculations.9−12.However,we have approximated the potential by a series of linear potentials and we have included small slopes(10−3¯hωc/ℓ),on the plateaus and in the central region,to include,in a simple fashion,the eﬀects of imperfect screening. These slopes are too small to be resolved in Fig3.We shall show that this piecewise linear potential,which supports a low-temperature density distribution consisting of wide compressible edge channels and narrow incompressible strips,is suﬃcient to accurately characterize the low-temperature current distribution in a narrow Hall bar.In Fig.4,we plot the low-temperature(k B T=0.002¯hωc)density and current distribu-tions in the conﬁning potential of Fig.3.The large number of fractionally occupied states in the compressible edge regions leads to smooth edge proﬁles(solid curve).The edge channels occur in the plateaus of the potential,whereas the incompressible strips occur at the potential steps.The current distribution(dashed curve)consists of edge currentsin the compressible regions and bulk currents in the incompressible regions.Small steps occur in the density(at x=±15ℓ)and current density(at x=0)because of the sharp corners in our piecewise linear potential.B.Universal integrated currentsIn the ideal case of perfect compressibility and incompressibility,only one type of current contributes to a given region.We now show that,in this ideal case,the integrated currents in these regions are universal,independent of the size and position of the regions, and the geometry of the sample.It is easy to calculate total current carried in each edge channel and in each incompressible strip(we neglect incompressible strips at fractional ﬁlling factors).From(1.1),we see that the integrated edge current depends only on the net density change across the edge channel,which is(2πℓ2)−1at low temperatures,and on the index n of the Landau states which form the edge.Therefore,an edge channel at the edge of the n th Landau level carries a current of magnitudeI edge,n=(n+1,(4.1)2πindependent of the width and position of the edge channel.A central compressible region which supports no net density change across its boundaries,carries no integrated current. From(1.2),we see that the integrated bulk current in an incompressible strip with integral ﬁlling factorνis simplyeωcI bulk=νC.Quantized persistent currentsAs aﬁnal application of our result,we shall investigate the quantization of the per-sistent current(total azimuthal current through a radial cross section)in a quantum dot predicted recently by Avishai and Kohmoto24.Consider a system of noninteracting elec-trons in a slowly varying cylindrically symmetric potential V(r)subjected to a uniform magneticﬁeld B=B e z.The quantum dot is assumed to be large enough so that there are many degenerate Landau states in the bulk.The ground-state radial density and current distributions will be similar to those in Figs.1and2(with x acting as a radial coordi-nate),except that the central incompressible region will be larger and the bulk currents will vanish there because of the assumedﬂatness of the conﬁning potential.Following Ref. 24,we shall calculate the integrated azimuthal currentI= ∞0dr j(r),(4.3) when the Fermi energy lies in a bulk Landau level.We shall initially assume,for simplicity, that the Fermi energy is just below Landau level n so that theﬁlling factor isν=n in the center of the dot.Afterwards,we treat the realistic situation where the Fermi energy is somewhere in the bulk states of Landau level n.We shall evaluate the persistent current by dividing the integral(4.3)into n regions of ﬁlling factor n,n−1,...,1.The central region is from r=0(where the azimuthal current density vanishes)to r=r′where V(r′)−V(0)=¯hωc,and has constantﬁlling factor ν=n.The integrated bulk current in this region is simply neωc/2π.The edge current concentrated about r=r′comes from states with Landau level index n−1and contributes an amount−(n−1Therefore,whenever the Fermi energy lies just below the bulk states of Landau level n, the persistent current is neωc/4π.As the number of electrons in the quantum dot is changed,the Fermi energy is generally pinned in a set of bulk states,not below them.Because the bulk states carry no bulk current,the persistent current calculated above is modiﬁed by the integrated edge current −(n+1.(4.4)4πAvishai and Kohmoto24have also predicted a persitent current which is quantized in integer multiples of eωc/4πas a function of particle number.ACKNOWLEDGMENTSThis work was supported by the National Science Foundation through Grant No. DMR-9100988.We thank Rolf Gerhardts,Yigal Meir,Boris Shklovskii,and David Thou-less,for providing us with preprints of their work.Here we calculate the integrated ground-state edge currents,I+n,which may be written asI+n≡g A n ∞0dx ∞−∞dKΘ[µ−¯hΩ(n+1ω2c V KL ]× K−x L)2H2n K−x2)−1,g≡(eωc/2πℓ)[1+(ω0/ωc)2]72H n+1+n H n−1and H′n=2nH n−1 lead toI+n=−1∂XH n(X−K) ,(A2) where X≡x/L,and where K n L,deﬁned byµ=¯hΩ(n+12H′n+1/(n+1),weﬁndI+n=−1∂X H 2n+1(X−K)2gL.Therefore,the zero-temperature integrated edge currents are equal toI±n=∓ n+12π 1+ω202,(A4) as stated.In this appendix,we shall derive the current distribution given in Section I from linear response theory to provide a deeper understanding of the result and to estab-lish the connection with the distribution derived from current-density functional theory.1 We start with a uniform electron gas in a magneticﬁeld B=B e z at low temperature (k B T<<¯hωc).The static current-current response functionχµν(q)(µ,ν=0,1,2),de-ﬁned by jµ(q)=χµν(q)Aν(q),describes the Fourier components of the three-current jµ≡(ρ,j)induced by the application of an inﬁnitesimal potential Aµ≡(V,A).Combin-ingχ00(q)andχi0(q)together leads to the nonlocal relationj i(q)=χi0(q)e¯h∂ρ/∂B µ∂B µ=ρ2πℓ2 e¯h2)F−1n(µ)(B3)and∂ρ2πℓ2 n F−1n(µ),(B4) where F n(µ)≡4k B T cosh2 [µ−¯hωc(n+12)with a width of order k B T.Note that thedenominator in(B2)is positive deﬁnite,whereas the numerator is a sum of two terms with opposite signs.We shall show that theﬁrst term in(B3)largely determines the current density in the incompressible regions while the second term largely determines the current in the compressible regions.In a compressible region nearﬁlling factorν=n+12).The narrow range|µ−¯hωc|≤k B T corresponds to the entire range of compressible densities.Because only a single term contributes to the summations(apart from terms exponentially small in k B T/¯hωc),γ=−2ρ∂µ−1B+(2n+1).(B5)Then∇ρ=− ∂ρ/∂µ B∇V leads to the distribution given in(1.1)and(1.2),atﬁlling factorν=n+1REFERENCES1G.Vignale and P.Skudlarski,Phys.Rev.B46,10232(1992).See also G.Vignale, in Proceedings of the NATO ASI on Density Functional Theory,edited by E.K.U. Gross and R.M.Dreizler(in press).2G.Vignale and M.Rasolt,Phys.Rev.Lett.59,2360(1987);Phys.Rev.B37, 10685(1988).3C.W.J.Beenakker and H.van Houten,in Solid State Physics Vol.44,edited by H.Ehrenreich and D.Turnbull(Academic Press,New York,1991).4M.B¨u ttiker,in Semiconductors and Semimetals Vol.35,edited by M.Reed(Aca-demic Press,New York,1992).5D.B.Chklovskii,B.I.Shklovskii,and L.I.Glazman,Phys.Rev.B46,4026(1992). 6P.L.McEuen et al.,Phys.Rev B45,11419(1992).7D.B.Chklovskii,K.A.Matveev,and B.I.Shklovskii,Phys.Rev.B47,12605 (1993).8M.M.Fogler,E.I.Levin,and B.I.Shklovskii(to be published).9B.Y.Gelfand and B.I.Halperin,Phys.Rev.B49,1862(1994).10L.Brey,J.J.Palacios,and C.Tejedor,Phys.Rev.B47,13884(1993).11C.Wexler and D.J.Thouless,Phys.Rev.B49,4815(1994).12K.Lier and R.R.Gerhardts,(to be published).13C.de C.Chamon and X.G.Wen,Phys.Rev.B49,8227(1994).14Y.Meir,Phys.Rev.Lett.72,2624(1994).15A.H.MacDonald,T.M.Rice,and W.F.Brinkman,Phys.Rev.B28,3648(1983). 16O.Heinonen and P.L.Taylor,Phys.Rev.B32,633(1985).17D.J.Thouless,J.Phys.C18,6211(1985).18Q.Li and D.J.Thouless,Phys.Rev.Lett.65,767(1990).19D.Pfannkuche and J.Hajdu,Phys.Rev.B46,7032(1992).20D.J.Thouless,Phys.Rev.Lett.71,1879(1993).21O.Heinonen and M.D.Johnson,Phys.Rev Lett.71,1447(1993).22T.K.Ng,Phys.Rev.Lett.68,1018(1992).23S.Hershﬁeld,Phys.Rev.Lett.70,2134(1993).24Y.Avishai and M.Kohmoto,Phys.Rev.Lett.71,279(1993).FIGURE CAPTIONSFIG.1.Ground-state density,ρ(x),in a parabolic potential with curvatureω0=1¯hωc.Lengths are plotted in units of magnetic lengthℓ.2FIG.4.Equilibrium density(solid curve)and current density(dashed curve)corre-sponding to the stepped conﬁning potential and chemical potential of Fig.3,at low temperature(k B T=0.002¯hωc).The density is plotted in units ofρ0≡(2πℓ2)−1andthe current density is plotted in units of j0≡eωc/2πℓ.Lengths are plotted in units of magnetic lengthℓ.Note the alternating directions,or signs,of the edge and bulk currents.。

生物专业英语翻译

第一课Cytoplasm: The Dynamic, Mobile Factory细胞质：动力工厂Most of the properties we associate with life are properties of the cytoplasm. Much of the mass of a cell consists of this semifluid substance, which is bounded on the outside by the plasma membrane. Organelles are suspended within it, supported by the filamentous network of the cytoskeleton. Dissolved in the cytoplasmic fluid are nutrients, ions, soluble proteins, and other materials needed for cell functioning.生命的大部分特征表现在细胞质的特征上。

细胞质大部分由半流体物质组成，并由细胞膜（原生质膜）包被。

细胞器悬浮在其中，并由丝状的细胞骨架支撑。

细胞质中溶解了大量的营养物质，离子，可溶蛋白以及维持细胞生理需求的其它物质。

The Nucleus: Information Central（细胞核：信息中心）The eukaryotic cell nucleus is the largest organelle and houses the genetic material (DNA) on chromosomes. (In prokaryotes the hereditary material is found in the nucleoid.) The nucleus also contains one or two organelles-the nucleoli-that play a role in cell division. A pore-perforated sac called the nuclear envelope separates the nucleus and its contents from the cytoplasm. Small molecules can pass through the nuclear envelope, but larger molecules such as mRNA and ribosomes must enter and exit via the pores.真核细胞的细胞核是最大的细胞器，细胞核对染色体组有保护作用（原核细胞的遗传物质存在于拟核中）。