Generalized thermoelastic interaction in functional graded material with fractional order

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附引进人员教育经历及代表成果1.李博-西安石油大学

3．Aerothermoelastic stability of viscoelastic panels with aerodynamic loading on both sides,Journal of Sound and Vibration 排名 1,SCI 收录 4．Aeroelastic stability analysis of heated flexible panel to an oblick shock,Chinese Journal of Aeronautics,排名 3,SCI 收录 5. The nonlinear aeroelastic characteristics of a folding wing with cubic stiffness， Journal of Sound and Vibration, 排名 4,SCI 收录 Analysis of nonlinear aeroelastic characteristics of a trapezoidal wing in hypersonic flow, Nonlinear Dynamics, 排名 4,SCI 收录 6. Deformation behavior of isothermally forged Ti-5Al-2Sn-2Zr-4Mo-4Cr Powder compact，Journal of Materials Pro Tech，排名 3,SCI 收录 7．两面受气动载荷的粘弹性壁板热气动弹性稳定性分析，航空航天学术研讨会，排名 1 8．热处理对 β 相区热处理 TC21 钛合金锻件组织性能的影响. 航空材料学报，排名 1，EI 收录 9．损伤容限型钛合金的等温锻造温度研究.锻压技术,排名 1,中文核心 10. 600MW 机组汽轮机低压转子叶片断裂原因分析.热加工工艺，排名 2,中文核心

高分子物理名词解释

高分子物理名词解释Θ溶剂(Θ solvent)：链段-溶剂相互吸引刚好抵消链段间空间排斥的溶剂，形成高分子溶液时观察不到远程作用，该溶剂中的高分子链的行为同无扰链2.7Θ温度(Θ temperature)：溶剂表现出Θ溶剂性质的温度2.7Argon理论(Argon theory)：一种银纹扩展过程的模型，描述了分子链被伸展将聚合物材料空化的过程5.3Avrami方程(Avrami equation)：描述物质结晶转化率与时间关系的方程：--α，α为转化率，K与n称Avrami常数(Avrami constants) 4.8 =Kt1n)ex p(Bingham流体(Bingham liquid)：此类流体具有一个屈服应力σy，应力低于σy时不产生形变，当应力大于σy时才发生流动，应力高于σy的部分与应变速率呈线性关系3.13 Boltzmann叠加原理(Blotzmann superposition principle)：Boltzmann提出的粘弹性原理：认为样品在不同时刻对应力或应变的响应各自独立并可线性叠加 3.8Bravais晶格(Bravais lattice)：结构单元在空间的排列方式4.1Burger's模型(Burger's model)：由一个Maxwell模型和一个Kelvin模型串联构成的粘弹性模型3.7Cauchy应变(Cauchy strain)：拉伸引起的相对于样品初始长度的形变分数，又称工程应变3.16Charpy冲击测试(Charpy impact test)：样品以简支梁形式放置的冲击强度测试，测量样品单位截面积的冲击能5.4Considère构图(Considère construction)：以真应力对工程应作图以判定细颈稳定性的方法5.2Eyring模型(Eyring model)：一种描述材料形变过程的分子模型，认为形变是结构单元越过能垒的跳跃式运动5.2Flory-Huggins参数(Flory-Huggins interaction parameter)：描述聚合物链段与溶剂分子间相互作用的参数，常用χ表示，物理意义为一个溶质分子被放入溶剂中作用能变化与动能之比2.11.2Flory构图(Flory construction)：保持固定拉伸比所需的力f对实验温度作图得到，由截距确定内能对拉伸力的贡献，由斜率确定熵对拉伸力的贡献2.16.2Flory特征比(characteristic ratio)：无扰链均方末端距与自由连接链均方末端距的比值2.4 Griffith理论(Griffith theory)：一种描述材料断裂机理的理论，认为断裂是吸收外界能量产生新表面的过程5.4Hencky应变(Hencky strain)：拉伸引起的相对于样品形变分数积分，又称真应变3.16 Hermans取向因子(Hermans orientation factor)：描述结构单元取向程度的参数，是结构单元与参考方向夹角余弦均方值的函数4.8, 4.10Hoffman-Weeks作图法(Hoffman-Weeks plot)：一种确定平衡熔点的方法。

设计具有高热稳定性的莫内林变体

设计具有高热稳定性的莫内林变体
作者：
来源：《科学中国人》2024年第02期
天津大学生命科学学院刘斯、叶升团队通过计算设计成功创造出4种能够在沸水中仍保持甜度的莫内林（Monellin）突变体，解决了莫内林甜蛋白在开发中的一个重要挑战。

相關成果发表于《食品化学》（Food Chemistry）。

莫内林是一种源自非洲植物浆果的小型植物蛋白，具有低热量、高甜度和丰富营养的特点，是一种具有潜在高附加值的食品甜味剂。

研究团队最终得到4种突变体表现出显著改善的热稳定性，即使在沸水中加热一小时后，这些突变体仍保持溶解。

此外，它们在碱性、酸性和中性环境中表现出卓越的稳定性。

这些发现强调了这些突变体在食品和饮料行业应用中的潜力。

常用化工热力学英语词汇

体积膨胀系数
Volume expansivity
理想功
Ideal wsystem
理想气体
Ideal gas
无孔膜
Membrane-nonporous
理想溶液
Ideal solution
相对挥发度
Relative volatility
临界点
Critical point
等熵效率
Isentropic efficiency
Lewis-Randall 规则
Lewis-Randall rule
等温压缩系数
Isothermal compressibility
Poynting 因子
Poynting factor
对比态原理
Theorem of corresponding state
热容
Heat capacity
化学反应平衡转化率
Equilibrium conversion for chemical reaction
热效应
Heat effect
混合规则
Mixing rule
三相点
Triple point
混合过程
Mixing process
闪蒸
Flash
活度
Activity
熵
Entropy
焓
Enthalpy
标准态
Standard state
恒沸点
Azeotrope
部分互溶系统
Partially miscible system
热泵
Heat pump
化学位
Chemical potential
热力学效率
Thermodynamics efficiency

科技论文写作-第四章-PPT课件

注意下例中红字表示的名词、代词或名词短语。
4.2 背景资料（步骤一）
4.2.2 时态与“先旧后新”原则
例4-2
Delaminations in composite materials result typically from impact damage or manufacturing imperfections. In general, they cause a considerable reduction in compressive strength and therefore reduce the performance advantage of composite materials[1]. One mechanism of compressive strength reduction in delaminated composites is buckling out of plane of the groups of plies above and below the delamination. This buckling subjects the remaining unbuckled plies to asymmetric loading, resulting in a reduced failure load for the laminate.
第四章背景材料与文献回顾 4.1 基本内容及组织形式
几乎每一篇科技研究论文的导论中都会包含上述四个步骤。而步骤五、六可有可无。步骤五，指出本研究工作的理论价值或应用价值。步骤六，说明本研究论文的组织结构，以便读者对作者介绍研究结果的方式有大致的了解。
4.2 背景资料（步骤一） 4.2.1 背景资料的介绍
4.2.1 背景资料的介绍

生物物理化学实验报告——ITC

结构化学实验报告等温滴定量热法测定两种蛋白质间相互作用2012/5/5实验目的：了解MicroCal iTC200等温滴定量热仪在测量蛋白质相互作用中的应用，了解仪器基本工作原理，学习蛋白质相互作用的测定步骤和仪器操作，简要分析实验结果。

实验原理：在研究两种或两种以上的蛋白质的功能时，相关蛋白质之间常常存在相互作用（常常是氢键或范德华力），如果两蛋白可以彼此结合，则结合的过程中会放出一定的热量。

所以，通过测定蛋白质相互作用时放出热量的大小，可以得到蛋白相互作用时的结合常数K D、化学计量比N和焓变ΔH，从而由热力学公式ΔG = RT lnK D和ΔG = ΔH -TΔS可以进一步得到反应的自由能变化。

MicroCal iTC200等温滴定量热仪的基本原理就是实现了蛋白质之间的微量滴定操作和微小热量的精密测量。

通过滴定操作和热量的测量，量热仪可以给出热量-摩尔比曲线：图像中曲线的突跃中点对应的化学计量比就是两种蛋白质相互作用的化学计量数N ，突跃中点处曲线的斜率就是两种蛋白相互作用的结合常数K D 。

决定曲线形状的主要参数是C 值：C = 滴定池中的蛋白浓度/ KD = [M]tot/ KD × NC 值越大，曲线越陡；C 值越小，曲线越平缓，没有明显的突跃。

一般C 值在10-100之间实验效果最好。

实验材料：蛋白质tse1（17KD）蛋白质tsi1（16KD）实验步骤：1.使用紫外分光光度计在280nm检测波长下测定蛋白质溶液中蛋白质的浓度，根据所需要的蛋白质浓度比稀释蛋白质溶液。

2.在量热仪的注射器和样品池中分别加入两种不同的蛋白质样品。

⑴注射器加样①将装有约100微升样品的PCR管放入样品试管槽。

②注射器移到“Rest Position”；然后左手转动注射器上端，使注射器的连接孔对准支架上的孔。

右手将白色细管顶部的连接头水平对准注射器连接孔，先轻轻将乳白色连接头旋入连接孔，随后将乳白色连接头后的金属连接头轻轻拧紧即可。

高温超导体的红外光学响应

高温超导体的红外光学响应英文回答：High-temperature superconductors (HTS) are materials that exhibit superconductivity at relatively high temperatures, compared to traditional superconductors. These materials have a wide range of applications, including in the field of infrared (IR) optics. The IR optical response of HTS materials is of great interest due to their potential use in various devices and systems.The IR optical response of HTS materials refers to how these materials interact with infrared light. This interaction can be characterized by various parameters, such as reflectivity, transmittance, and absorbance. These parameters determine how much of the incident IR light is reflected, transmitted, or absorbed by the HTS material.One important aspect of the IR optical response of HTS materials is their reflectivity. Reflectivity is a measureof how much of the incident IR light is reflected by the material. In the case of HTS materials, their reflectivity can be influenced by factors such as the material's crystal structure, composition, and surface quality. For example, a smooth and polished surface of an HTS material may have higher reflectivity compared to a rough or oxidized surface.Another important parameter is transmittance, which refers to the fraction of incident IR light that passes through the material. The transmittance of HTS materialscan be affected by factors such as the material's thickness, impurities, and defects. For instance, a thicker HTSmaterial may have lower transmittance compared to a thinner one due to increased absorption and scattering of the IR light.Absorbance is a measure of how much of the incident IR light is absorbed by the material. The absorbance of HTS materials can be influenced by factors such as thematerial's energy gap, impurity levels, and temperature.For example, at certain IR frequencies, HTS materials may exhibit strong absorbance due to their energy gap matchingthe energy of the incident light.Understanding the IR optical response of HTS materialsis crucial for the design and optimization of devices and systems that utilize these materials. For example, in the field of IR detectors, the IR optical response of HTS materials can affect their sensitivity and performance. By studying and manipulating the IR optical response, researchers can develop HTS-based devices with enhanced performance and capabilities.中文回答：高温超导体（HTS）是相对于传统超导体而言，在相对较高的温度下表现出超导性的材料。

大环多胺

New1H-Pyrazole-Containing Polyamine Receptors Able ToComplex L-Glutamate in Water at Physiological pH ValuesCarlos Miranda,†Francisco Escartı´,‡Laurent Lamarque,†Marı´a J.R.Yunta,§Pilar Navarro,*,†Enrique Garcı´a-Espan˜a,*,‡and M.Luisa Jimeno†Contribution from the Instituto de Quı´mica Me´dica,Centro de Quı´mica Orga´nica Manuel Lora Tamayo,CSIC,C/Juan de la Cier V a3,28006Madrid,Spain,Departamento de Quı´mica Inorga´nica,Facultad de Quı´mica,Uni V ersidad de Valencia,c/Doctor Moliner50, 46100Burjassot(Valencia),Spain,and Departamento de Quı´mica Orga´nica,Facultad deQuı´mica,Uni V ersidad Complutense de Madrid,A V plutense s/n,28040Madrid,SpainReceived April16,2003;E-mail:enrique.garcia-es@uv.esAbstract:The interaction of the pyrazole-containing macrocyclic receptors3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene1[L1],13,26-dibenzyl-3,6,9,12,13,16,-19,22,25,26-decaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene2[L2],3,9,12,13,16,22,-25,26-octaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene3[L3],6,19-dibenzyl-3,6,9,12,13,-16,19,22,25,26-decaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene4[L4],6,19-diphenethyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetraene5[L5],and 6,19-dioctyl-3,6,9,12,13,16,19,22,25,26-decaazatricyclo-[22.2.1.111,14]-octacosa-1(27),11,14(28),24-tetra-ene6[L6]with L-glutamate in aqueous solution has been studied by potentiometric techniques.The synthesis of receptors3-6[L3-L6]is described for the first time.The potentiometric results show that4[L4]containing benzyl groups in the central nitrogens of the polyamine side chains is the receptor displaying the larger interaction at pH7.4(K eff)2.04×104).The presence of phenethyl5[L5]or octyl groups6[L6]instead of benzyl groups4[L4]in the central nitrogens of the chains produces a drastic decrease in the stability[K eff )3.51×102(5),K eff)3.64×102(6)].The studies show the relevance of the central polyaminic nitrogen in the interaction with glutamate.1[L1]and2[L2]with secondary nitrogens in this position present significantly larger interactions than3[L3],which lacks an amino group in the center of the chains.The NMR and modeling studies suggest the important contribution of hydrogen bonding andπ-cation interaction to adduct formation.IntroductionThe search for the L-glutamate receptor field has been andcontinues to be in a state of almost explosive development.1 L-Glutamate(Glu)is thought to be the predominant excitatory transmitter in the central nervous system(CNS)acting at a rangeof excitatory amino acid receptors.It is well-known that it playsa vital role mediating a great part of the synaptic transmission.2However,there is an increasing amount of experimentalevidence that metabolic defects and glutamatergic abnormalitiescan exacerbate or induce glutamate-mediated excitotoxic damageand consequently neurological disorders.3,4Overactivation ofionotropic(NMDA,AMPA,and Kainate)receptors(iGluRs)by Glu yields an excessive Ca2+influx that produces irreversible loss of neurons of specific areas of the brain.5There is much evidence that these processes induce,at least in part,neuro-degenerative illnesses such as Parkinson,Alzheimer,Huntington, AIDS,dementia,and amyotrophic lateral sclerosis(ALS).6In particular,ALS is one of the neurodegenerative disorders for which there is more evidence that excitotoxicity due to an increase in Glu concentration may contribute to the pathology of the disease.7Memantine,a drug able to antagonize the pathological effects of sustained,but relatively small,increases in extracellular glutamate concentration,has been recently received for the treatment of Alzheimer disease.8However,there is not an effective treatment for ALS.Therefore,the preparation of adequately functionalized synthetic receptors for L-glutamate seems to be an important target in finding new routes for controlling abnormal excitatory processes.However,effective recognition in water of aminocarboxylic acids is not an easy task due to its zwitterionic character at physiological pH values and to the strong competition that it finds in its own solvent.9†Centro de Quı´mica Orga´nica Manuel Lora Tamayo.‡Universidad de Valencia.§Universidad Complutense de Madrid.(1)Jane,D.E.In Medicinal Chemistry into the Millenium;Campbell,M.M.,Blagbrough,I.S.,Eds.;Royal Society of Chemistry:Cambridge,2001;pp67-84.(2)(a)Standaert,D.G.;Young,A.B.In The Pharmacological Basis ofTherapeutics;Hardman,J.G.,Goodman Gilman,A.,Limbird,L.E.,Eds.;McGraw-Hill:New York,1996;Chapter22,p503.(b)Fletcher,E.J.;Loge,D.In An Introduction to Neurotransmission in Health and Disease;Riederer,P.,Kopp,N.,Pearson,J.,Eds.;Oxford University Press:New York,1990;Chapter7,p79.(3)Michaelis,E.K.Prog.Neurobiol.1998,54,369-415.(4)Olney,J.W.Science1969,164,719-721.(5)Green,J.G.;Greenamyre,J.T.Prog.Neurobiol.1996,48,613-63.(6)Bra¨un-Osborne,H.;Egebjerg,J.;Nielsen,E.O.;Madsen,U.;Krogsgaard-Larsen,P.J.Med.Chem.2000,43,2609-2645and references therein.(7)(a)Shaw,P.J.;Ince,P.G.J.Neurol.1997,244(Suppl2),S3-S14.(b)Plaitakis,A.;Fesdjian,C.O.;Shashidharan,S Drugs1996,5,437-456.(8)Frantz,A.;Smith,A.Nat.Re V.Drug Dico V ery2003,2,9.Published on Web12/30/200310.1021/ja035671m CCC:$27.50©2004American Chemical Society J.AM.CHEM.SOC.2004,126,823-8339823There are many types of receptors able to interact with carboxylic acids and amino acids in organic solvents,10-13yielding selective complexation in some instances.However,the number of reported receptors of glutamate in aqueous solution is very scarce.In this sense,one of the few reports concerns an optical sensor based on a Zn(II)complex of a 2,2′:6′,2′′-terpyridine derivative in which L -aspartate and L -glutamate were efficiently bound as axial ligands (K s )104-105M -1)in 50/50water/methanol mixtures.14Among the receptors employed for carboxylic acid recogni-tion,the polyamine macrocycles I -IV in Chart 1are of particular relevance to this work.In a seminal paper,Lehn et al.15showed that saturated polyamines I and II could exert chain-length discrimination between different R ,ω-dicarboxylic acids as a function of the number of methylene groups between the two triamine units of the receptor.Such compounds were also able to interact with a glutamic acid derivative which has the ammonium group protected with an acyl moiety.15,16Compounds III and IV reported by Gotor and Lehn interact in their protonated forms in aqueous solution with protected N -acetyl-L -glutamate and N -acetyl-D -glutamate,showing a higher stability for the interaction with the D -isomer.17In both reports,the interaction with protected N -acetyl-L -glutamate at physiological pH yields constants of ca.3logarithmic units.Recently,we have shown that 1H -pyrazole-containing mac-rocycles present desirable properties for the binding of dopam-ine.18These polyaza macrocycles,apart from having a highpositive charge at neutral pH values,can form hydrogen bonds not only through the ammonium or amine groups but also through the pyrazole nitrogens that can behave as hydrogen bond donors or acceptors.In fact,Elguero et al.19have recently shown the ability of the pyrazole rings to form hydrogen bonds with carboxylic and carboxylate functions.These features can be used to recognize the functionalities of glutamic acid,the carboxylic and/or carboxylate functions and the ammonium group.Apart from this,the introduction of aromatic donor groups appropriately arranged within the macrocyclic framework or appended to it through arms of adequate length may contribute to the recognition event through π-cation interactions with the ammonium group of L -glutamate.π-Cation interactions are a key feature in many enzymatic centers,a classical example being acetylcholine esterase.20The role of such an interaction in abiotic systems was very well illustrated several years ago in a seminal work carried out by Dougherty and Stauffer.21Since then,many other examples have been reported both in biotic and in abiotic systems.22Taking into account all of these considerations,here we report on the ability of receptors 1[L 1]-6[L 6](Chart 2)to interact with L -glutamic acid.These receptors display structures which differ from one another in only one feature,which helps to obtain clear-cut relations between structure and interaction(9)Rebek,J.,Jr.;Askew,B.;Nemeth,D.;Parris,K.J.Am.Chem.Soc.1987,109,2432-2434.(10)Seel,C.;de Mendoza,J.In Comprehensi V e Supramolecular Chemistry ;Vogtle,F.,Ed.;Elsevier Science:New York,1996;Vol.2,p 519.(11)(a)Sessler,J.L.;Sanson,P.I.;Andrievesky,A.;Kral,V.In SupramolecularChemistry of Anions ;Bianchi,A.,Bowman-James,K.,Garcı´a-Espan ˜a,E.,Eds.;John Wiley &Sons:New York,1997;Chapter 10,pp 369-375.(b)Sessler,J.L.;Andrievsky,A.;Kra ´l,V.;Lynch,V.J.Am.Chem.Soc.1997,119,9385-9392.(12)Fitzmaurice,R.J.;Kyne,G.M.;Douheret,D.;Kilburn,J.D.J.Chem.Soc.,Perkin Trans.12002,7,841-864and references therein.(13)Rossi,S.;Kyne,G.M.;Turner,D.L.;Wells,N.J.;Kilburn,J.D.Angew.Chem.,Int.Ed.2002,41,4233-4236.(14)Aı¨t-Haddou,H.;Wiskur,S.L.;Lynch,V.M.;Anslyn,E.V.J.Am.Chem.Soc.2001,123,11296-11297.(15)Hosseini,M.W.;Lehn,J.-M.J.Am.Chem.Soc.1982,104,3525-3527.(16)(a)Hosseini,M.W.;Lehn,J.-M.Hel V .Chim.Acta 1986,69,587-603.(b)Heyer,D.;Lehn,J.-M.Tetrahedron Lett.1986,27,5869-5872.(17)(a)Alfonso,I.;Dietrich,B.;Rebolledo,F.;Gotor,V.;Lehn,J.-M.Hel V .Chim.Acta 2001,84,280-295.(b)Alfonso,I.;Rebolledo,F.;Gotor,V.Chem.-Eur.J.2000,6,3331-3338.(18)Lamarque,L.;Navarro,P.;Miranda,C.;Ara ´n,V.J.;Ochoa,C.;Escartı´,F.;Garcı´a-Espan ˜a,E.;Latorre,J.;Luis,S.V.;Miravet,J.F.J.Am.Chem.Soc .2001,123,10560-10570.(19)Foces-Foces,C.;Echevarria,A.;Jagerovic,N.;Alkorta,I.;Elguero,J.;Langer,U.;Klein,O.;Minguet-Bonvehı´,H.-H.J.Am.Chem.Soc.2001,123,7898-7906.(20)Sussman,J.L.;Harel,M.;Frolow,F.;Oefner,C.;Goldman,A.;Toker,L.;Silman,I.Science 1991,253,872-879.(21)Dougherty,D.A.;Stauffer,D.A.Science 1990,250,1558-1560.(22)(a)Sutcliffe,M.J.;Smeeton,A.H.;Wo,Z.G.;Oswald,R.E.FaradayDiscuss.1998,111,259-272.(b)Kearney,P.C.;Mizoue,L.S.;Kumpf,R.A.;Forman,J.E.;McCurdy,A.;Dougherty,D.A.J.Am.Chem.Soc.1993,115,9907-9919.(c)Bra ¨uner-Osborne,H.;Egebjerg,J.;Nielsen,E.;Madsen,U.;Krogsgaard-Larsen,P.J.Med.Chem.2000,43,2609-2645.(d)Zacharias,N.;Dougherty,D.A.Trends Pharmacol.Sci.2002,23,281-287.(e)Hu,J.;Barbour,L.J.;Gokel,G.W.J.Am.Chem.Soc.2002,124,10940-10941.Chart 1.Some Receptors Employed for Dicarboxylic Acid and N -AcetylglutamateRecognitionChart 2.New 1H -Pyrazole-Containing Polyamine Receptors Able To Complex L -Glutamate inWaterA R T I C L E SMiranda et al.824J.AM.CHEM.SOC.9VOL.126,NO.3,2004strengths.1[L1]and2[L2]differ in the N-benzylation of the pyrazole moiety,and1[L1]and3[L3]differ in the presence in the center of the polyamine side chains of an amino group or of a methylene group.The receptors4[L4]and5[L5]present the central nitrogens of the chain N-functionalized with benzyl or phenethyl groups,and6[L6]has large hydrophobic octyl groups.Results and DiscussionSynthesis of3-6.Macrocycles3-6have been obtained following the procedure previously reported for the preparation of1and2.23The method includes a first dipodal(2+2) condensation of the1H-pyrazol-3,5-dicarbaldehyde7with the corresponding R,ω-diamine,followed by hydrogenation of the resulting Schiff base imine bonds.In the case of receptor3,the Schiff base formed by condensation with1,5-pentanediamine is a stable solid(8,mp208-210°C)which precipitated in68% yield from the reaction mixture.Further reduction with NaBH4 in absolute ethanol gave the expected tetraazamacrocycle3, which after crystallization from toluene was isolated as a pure compound(mp184-186°C).In the cases of receptors4-6, the precursor R,ω-diamines(11a-11c)(Scheme1B)were obtained,by using a procedure previously described for11a.24 This procedure is based on the previous protection of the primary amino groups of1,5-diamino-3-azapentane by treatment with phthalic anhydride,followed by alkylation of the secondary amino group of1,5-diphthalimido-3-azapentane9with benzyl, phenethyl,or octyl bromide.Finally,the phthalimido groups of the N-alkyl substituted intermediates10a-10c were removed by treatment with hydrazine to afford the desired amines11a-11c,which were obtained in moderate yield(54-63%).In contrast with the behavior previously observed in the synthesis of3,in the(2+2)dipodal condensations of7with 3-benzyl-,3-phenethyl-,and3-octyl-substituted3-aza-1,5-pentanediamine11a,11b,and11c,respectively,there was not precipitation of the expected Schiff bases(Scheme1A). Consequently,the reaction mixtures were directly reduced in situ with NaBH4to obtain the desired hexaamines4-6,which after being carefully purified by chromatography afforded purecolorless oils in51%,63%,and31%yield,respectively.The structures of all of these new cyclic polyamines have been established from the analytical and spectroscopic data(MS(ES+), 1H and13C NMR)of both the free ligands3-6and their corresponding hydrochloride salts[3‚4HCl,4‚6HCl,5‚6HCl, and6‚6HCl],which were obtained as stable solids following the same procedure previously reported18for1‚6HCl and2‚6HCl.As usually occurs for3,5-disubstituted1H-pyrazole deriva-tives,either the free ligands3-6or their hydrochlorides show very simple1H and13C NMR spectra,in which signals indicate that,because of the prototropic equilibrium of the pyrazole ring, all of these compounds present average4-fold symmetry on the NMR scale.The quaternary C3and C5carbons appear together,and the pairs of methylene carbons C6,C7,and C8are magnetically equivalent(see Experimental Section).In the13C NMR spectra registered in CDCl3solution, significant differences can be observed between ligand3,without an amino group in the center of the side chain,and the N-substituted ligands4-6.In3,the C3,5signal appears as a broad singlet.However,in4-6,it almost disappears within the baseline of the spectra,and the methylene carbon atoms C6and C8experience a significant broadening.Additionally,a remark-able line-broadening is also observed in the C1′carbon signals belonging to the phenethyl and octyl groups of L5and L6, respectively.All of these data suggest that as the N-substituents located in the middle of the side chains of4-6are larger,the dynamic exchange rate of the pyrazole prototropic equilibrium is gradually lower,probably due to a relation between proto-tropic and conformational equilibria.Acid-Base Behavior.To follow the complexation of L-glutamate(hereafter abbreviated as Glu2-)and its protonated forms(HGlu-,H2Glu,and H3Glu+)by the receptors L1-L6, the acid-base behavior of L-glutamate has to be revisited under the experimental conditions of this work,298K and0.15mol dm-3.The protonation constants obtained,included in the first column of Table1,agree with the literature25and show that the zwitterionic HGlu-species is the only species present in aqueous solution at physiological pH values(Scheme2and Figure S1of Supporting Information).Therefore,receptors for(23)Ara´n,V.J.;Kumar,M.;Molina,J.;Lamarque,L.;Navarro,P.;Garcı´a-Espan˜a,E.;Ramı´rez,J.A.;Luis,S.V.;Escuder,.Chem.1999, 64,6137-6146.(24)(a)Yuen Ng,C.;Motekaitis,R.J.;Martell,A.E.Inorg.Chem.1979,18,2982-2986.(b)Anelli,P.L.;Lunazzi,L.;Montanari,F.;Quici,.Chem.1984,49,4197-4203.Scheme1.Synthesis of the Pyrazole-Containing MacrocyclicReceptorsNew1H-Pyrazole-Containing Polyamine Receptors A R T I C L E SJ.AM.CHEM.SOC.9VOL.126,NO.3,2004825glutamate recognition able to address both the negative charges of the carboxylate groups and the positive charge of ammonium are highly relevant.The protonation constants of L 3-L 6are included in Table 1,together with those we have previously reported for receptors L 1and L 2.23A comparison of the constants of L 4-L 6with those of the nonfunctionalized receptor L 1shows a reduced basicity of the receptors L 4-L 6with tertiary nitrogens at the middle of the polyamine bridges.Such a reduction in basicity prevented the potentiometric detection of the last protonation for these ligands in aqueous solution.A similar reduction in basicity was previously reported for the macrocycle with the N -benzylated pyrazole spacers (L 2).23These diminished basicities are related to the lower probability of the tertiary nitrogens for stabilizing the positive charges through hydrogen bond formation either with adjacent nonprotonated amino groups of the molecule or with water molecules.Also,the increase in the hydrophobicity of these molecules will contribute to their lower basicity.The stepwise basicity constants are relatively high for the first four protonation steps,which is attributable to the fact that these protons can bind to the nitrogen atoms adjacent to the pyrazole groups leaving the central nitrogen free,the electrostatic repulsions between them being therefore of little significance.The remaining protonation steps will occur in the central nitrogen atom,which will produce an important increase in the electrostatic repulsion in the molecule and therefore a reduction in basicity.As stated above,the tertiary nitrogen atoms present in L 4-L 6will also contribute to this diminished basicity.To analyze the interaction with glutamic acid,it is important to know the protonation degree of the ligands at physiological pH values.In Table 2,we have calculated the percentages ofthe different protonated species existing in solution at pH 7.4for receptors L 1-L 6.As can be seen,except for the receptor with the pentamethylenic chains L 3in which the tetraprotonated species prevails,all of the other systems show that the di-and triprotonated species prevail,although to different extents.Interaction with Glutamate.The stepwise constants for the interaction of the receptors L 1-L 6with glutamate are shown in Table 3,and selected distribution diagrams are plotted in Figure 1A -C.All of the studied receptors interact with glutamate forming adduct species with protonation degrees (j )which vary between 8and 0depending on the system (see Table 3).The stepwise constants have been derived from the overall association constants (L +Glu 2-+j H +)H j LGlu (j -2)+,log j )provided by the fitting of the pH-metric titration curves.This takes into account the basicities of the receptors and glutamate (vide supra)and the pH range in which a given species prevails in solution.In this respect,except below pH ca.4and above pH 9,HGlu -can be chosen as the protonated form of glutamate involved in the formation of the different adducts.Below pH 4,the participation of H 2Glu in the equilibria has also to be considered (entries 9and 10in Table 3).For instance,the formation of the H 6LGlu 4+species can proceed through the equilibria HGlu -+H 5L 5+)H 6LGlu 4+(entry 8,Table 3),and H 2Glu +H 4L 4+)H 6LGlu 4(entry 9Table 3),with percentages of participation that depend on pH.One of the effects of the interaction is to render somewhat more basic the receptor,and somewhat more acidic glutamic acid,facilitating the attraction between op-positely charged partners.A first inspection of Table 3and of the diagrams A,B,and C in Figure 1shows that the interaction strengths differ markedly from one system to another depending on the structural features of the receptors involved.L 4is the receptor that presents the highest capacity for interacting with glutamate throughout all of the pH range explored.It must also be remarked that there are not clear-cut trends in the values of the stepwise constants as a function of the protonation degree of the receptors.This suggests that charge -charge attractions do not play the most(25)(a)Martell,E.;Smith,R.M.Critical Stability Constants ;Plenum:NewYork,1975.(b)Motekaitis,R.J.NIST Critically Selected Stability Constants of Metal Complexes Database ;NIST Standard Reference Database,version 4,1997.Table 1.Protonation Constants of Glutamic Acid and Receptors L 1-L 6Determined in NaCl 0.15mol dm -3at 298.1KreactionGluL 1aL 2aL 3bL 4L 5L 6L +H )L H c 9.574(2)d 9.74(2)8.90(3)9.56(1)9.25(3)9.49(4)9.34(5)L H +H )L H 2 4.165(3)8.86(2)8.27(2)8.939(7)8.38(3)8.11(5)8.13(5)L H 2+H )L H 3 2.18(2)7.96(2) 6.62(3)8.02(1) 6.89(5)7.17(6)7.46(7)L H 3+H )L H 4 6.83(2) 5.85(4)7.63(1) 6.32(5) 6.35(6) 5.97(8)L H 4+H )L H 5 4.57(3) 3.37(4) 2.72(8) 2.84(9) 3.23(9)L H 5+H )L H 6 3.18(3) 2.27(6)∑log K H n L41.135.334.233.634.034.1aTaken from ref 23.b These data were previously cited in a short communication (ref 26).c Charges omitted for clarity.d Values in parentheses are the standard deviations in the last significant figure.Scheme 2.L -Glutamate Acid -BaseBehaviorTable 2.Percentages of the Different Protonated Species at pH 7.4H 1L aH 2LH 3LH 4LL 11186417L 21077130L 3083458L 4083458L 51154323L 6842482aCharges omitted for clarity.A R T I C L E SMiranda et al.826J.AM.CHEM.SOC.9VOL.126,NO.3,2004outstanding role and that other forces contribute very importantly to these processes.26However,in systems such as these,which present overlapping equilibria,it is convenient to use conditional constants because they provide a clearer picture of the selectivity trends.27These constants are defined as the quotient between the overall amounts of complexed species and those of free receptor and substrate at a given pH[eq1].In Figure2are presented the logarithms of the effective constants versus pH for all of the studied systems.Receptors L1and L2with a nonfunctionalized secondary amino group in the side chains display opposite trend from all other receptors. While the stability of the L1and L2adducts tends to increase with pH,the other ligands show a decreasing interaction. Additionally,L1and L2present a close interaction over the entire pH range under study.The tetraaminic macrocycle L3is a better(26)Escartı´,F.;Miranda,C.;Lamarque,L.;Latorre,J.;Garcı´a-Espan˜a,E.;Kumar,M.;Ara´n,V.J.;Navarro,mun.2002,9,936-937.(27)(a)Bianchi,A.;Garcı´a-Espan˜a,c.1999,12,1725-1732.(b)Aguilar,J.A.;Celda,B.;Garcı´a-Espan˜a,E.;Luis,S.V.;Martı´nez,M.;Ramı´rez,J.A.;Soriano,C.;Tejero,B.J.Chem.Soc.,Perkin Trans.22000, 7,1323-1328.Table3.Stability Constants for the Interaction of L1-L6with the Different Protonated Forms of Glutamate(Glu) entry reaction a L1L2L3L4L5L6 1Glu+L)Glu L 3.30(2)b 4.11(1)2HGlu+L)HGlu L 3.65(2) 4.11(1) 3.68(2) 3.38(4) 3Glu+H L)HGlu L 3.89(2) 4.48(1) 3.96(2) 3.57(4) 4HGlu+H L)H2Glu L 3.49(2) 3.89(1) 2.37(4) 3.71(2)5HGlu+H2L)H3Glu L 3.44(2) 3.73(1) 2.34(3) 4.14(2) 2.46(4) 2.61(7) 6HGlu+H3L)H4Glu L 3.33(2) 3.56(2) 2.66(3) 4.65(2) 2.74(3) 2.55(7) 7HGlu+H4L)H5Glu L 3.02(2) 3.26(2) 2.58(3) 4.77(2) 2.87(3) 2.91(5) 8HGlu+H5L)H6Glu L 3.11(3) 3.54(2) 6.76(3) 4.96(3) 4.47(3) 9H2Glu+H4L)H6Glu L 2.54(3) 3.05(2) 3.88(2) 5.35(3) 3.66(4) 3.56(3) 10H2Glu+H5L)H7Glu L 2.61(6) 2.73(4) 5.51(3) 3.57(4) 3.22(8) 11H3Glu+H4L)H7Glu L 4.82(2) 4.12(9)a Charges omitted for clarity.b Values in parentheses are standard deviations in the last significantfigure.Figure1.Distribution diagrams for the systems(A)L1-glutamic acid, (B)L4-glutamic acid,and(C)L5-glutamicacid.Figure2.Representation of the variation of K cond(M-1)for the interaction of glutamic acid with(A)L1and L3,(B)L2,L4,L5,and L6.Initial concentrations of glutamate and receptors are10-3mol dm-3.Kcond)∑[(H i L)‚(H j Glu)]/{∑[H i L]∑[H j Glu]}(1)New1H-Pyrazole-Containing Polyamine Receptors A R T I C L E SJ.AM.CHEM.SOC.9VOL.126,NO.3,2004827receptor at acidic pH,but its interaction markedly decreases on raising the pH.These results strongly suggest the implication of the central nitrogens of the lateral polyamine chains in the stabilization of the adducts.Among the N-functionalized receptors,L4presents the largest interaction with glutamate.Interestingly enough,L5,which differs from L4only in having a phenethyl group instead of a benzyl one,presents much lower stability of its adducts.Since the basicity and thereby the protonation states that L4and L5 present with pH are very close,the reason for the larger stability of the L4adducts could reside on a better spatial disposition for formingπ-cation interactions with the ammonium group of the amino acid.In addition,as already pointed out,L4presents the highest affinity for glutamic acid in a wide pH range,being overcome only by L1and L2at pH values over9.This observation again supports the contribution ofπ-cation inter-actions in the system L4-glutamic because at these pH values the ammonium functionality will start to deprotonate(see Scheme2and Figure1B).Table4gathers the percentages of the species existing in equilibria at pH7.4together with the values of the conditional constant at this pH.In correspondence with Figure1A,1C and Figure S2(Supporting Information),it can be seen that for L1, L2,L5,and L6the prevailing species are[H2L‚HGlu]+and[H3L‚HGlu]2+(protonation degrees3and4,respectively),while for L3the main species are[H3L‚HGlu]+and[H4L‚HGlu]2+ (protonation degrees4and5,respectively).The most effective receptor at this pH would be L4which joins hydrogen bonding, charge-charge,andπ-cation contributions for the stabilization of the adducts.To check the selectivity of this receptor,we have also studied its interaction with L-aspartate,which is a competitor of L-glutamate in the biologic receptors.The conditional constant at pH7.4has a value of3.1logarithmic units for the system Asp-L4.Therefore,the selectivity of L4 for glutamate over aspartate(K cond(L4-glu)/K cond(L4-asp))will be of ca.15.It is interesting to remark that the affinity of L4 for zwiterionic L-glutamate at pH7.4is even larger than that displayed by receptors III and IV(Chart1)with the protected dianion N-acetyl-L-glutamate lacking the zwitterionic charac-teristics.Applying eq1and the stability constants reported in ref17,conditional constants at pH7.4of 3.24and 2.96 logarithmic units can be derived for the systems III-L-Glu and IV-L-Glu,respectively.Molecular Modeling Studies.Molecular mechanics-based methods involving docking studies have been used to study the binding orientations and affinities for the complexation of glutamate by L1-L6receptors.The quality of a computer simulation depends on two factors:accuracy of the force field that describes intra-and intermolecular interactions,and an adequate sampling of the conformational and configuration space of the system.28The additive AMBER force field is appropriate for describing the complexation processes of our compounds,as it is one of the best methods29in reproducing H-bonding and stacking stabiliza-tion energies.The experimental data show that at pH7.4,L1-L6exist in different protonation states.So,a theoretical study of the protonation of these ligands was done,including all of the species shown in5%or more abundance in the potentiometric measurements(Table4).In each case,the more favored positions of protons were calculated for mono-,di-,tri-,and tetraprotonated species.Molecular dynamics studies were performed to find the minimum energy conformations with simulated solvent effects.Molecular modeling studies were carried out using the AMBER30method implemented in the Hyperchem6.0pack-age,31modified by the inclusion of appropriate parameters. Where available,the parameters came from analogous ones used in the literature.32All others were developed following Koll-man33and Hopfinger34procedures.The equilibrium bond length and angle values came from experimental values of reasonable reference compounds.All of the compounds were constructed using standard geometry and standard bond lengths.To develop suitable parameters for NH‚‚‚N hydrogen bonding,ab initio calculations at the STO-3G level35were used to calculate atomic charges compatible with the AMBER force field charges,as they gave excellent results,and,at the same time,this method allows the study of aryl-amine interactions.In all cases,full geometry optimizations with the Polak-Ribiere algorithm were carried out,with no restraints.Ions are separated far away and well solvated in water due to the fact that water has a high dielectric constant and hydrogen bond network.Consequently,there is no need to use counteri-ons36in the modelization studies.In the absence of explicit solvent molecules,a distance-dependent dielectric factor quali-tatively simulates the presence of water,as it takes into account the fact that the intermolecular electrostatic interactions should vanish more rapidly with distance than in the gas phase.The same results can be obtained using a constant dielectric factor greater than1.We have chosen to use a distance-dependent dielectric constant( )4R ij)as this was the method used by Weiner et al.37to develop the AMBER force field.Table8 shows the theoretical differences in protonation energy(∆E p) of mono-,bi-,and triprotonated hexaamine ligands,for the (28)Urban,J.J.;Cronin,C.W.;Roberts,R.R.;Famini,G.R.J.Am.Chem.Soc.1997,119,12292-12299.(29)Hobza,P.;Kabelac,M.;Sponer,J.;Mejzlik,P.;Vondrasek,put.Chem.1997,18,1136-1150.(30)Cornell,W.D.;Cieplak,P.;Bayly,C.I.;Gould,I.R.;Merz,K.M.,Jr.;Ferguson,D.M.;Spelmeyer,D.C.;Fox,T.;Caldwell,J.W.;Kollman,P.A.J.Am.Chem.Soc.1995,117,5179-5197.(31)Hyperchem6.0(Hypercube Inc.).(32)(a)Fox,T.;Scanlan,T.S.;Kollman,P.A.J.Am.Chem.Soc.1997,119,11571-11577.(b)Grootenhuis,P.D.;Kollman,P.A.J.Am.Chem.Soc.1989,111,2152-2158.(c)Moyna,G.;Hernandez,G.;Williams,H.J.;Nachman,R.J.;Scott,put.Sci.1997,37,951-956.(d)Boden,C.D.J.;Patenden,put.-Aided Mol.Des.1999, 13,153-166.(33)/amber.(34)Hopfinger,A.J.;Pearlstein,put.Chem.1984,5,486-499.(35)Glennon,T.M.;Zheng,Y.-J.;Le Grand,S.M.;Shutzberg,B.A.;Merz,K.M.,put.Chem.1994,15,1019-1040.(36)Wang,J.;Kollman,P.A.J.Am.Chem.Soc.1998,120,11106-11114.Table4.Percentages of the Different Protonated Adducts[HGlu‚H j L](j-1)+,Overall Percentages of Complexation,andConditional Constants(K Cond)at pH7.4for the Interaction ofGlutamate(HGlu-)with Receptors L1-L6at Physiological pH[H n L‚HGlu]an)1n)2n)3n)4∑{[H n L‚HGlu]}K cond(M-1)L13272353 2.44×103L2947763 4.12×103L31101324 3.99×102L423737581 2.04×104L51010222 3.51×102L6121224 3.64×102a Charges omitted for clarity.A R T I C L E S Miranda et al. 828J.AM.CHEM.SOC.9VOL.126,NO.3,2004。

First-principles study of the structural, vibrational, phonon and thermodynamic

1. Introduction Ultra-high temperature ceramics (UHTCs) with melting temperatures in excess of 3000 K are usually composed by the refractory borides, carbides and nitrides of early transition metals [1–7]. Among the UHTCs, transition metal carbides (TMC) such as TiC, ZrC and HfC are metallic compounds with unique physical and chemical properties including an extremely high melting point and hardness, chemical stability, corrosion resistance combined with metallic electrical and thermal conductivities [5–10]. These features give transition metal carbides the capability to withstand high temperatures in oxidizing environments, making them candidates for applications in the atmosphere of extreme thermal and chemical environments [6,7]. The structural, vibrational, phonon and thermodynamic properties of IVb group transition metal carbides have been investigated experimentally [10–17] and theoretically [13,18–28] in the earlier reports. In the 1970s, the phonon dispersion relations of TiC, ZrC and HfC were measured using inelastic neutron scattering by Pintschovius et al. [10] and Smith et al. [15–17]. Lattice dynamics calculation and the phonon dispersion relations of transition metal carbides such as ZrC and HfC were reported using a phenomenological ‘‘double-shell’’ model theory [18] where long-range interatomic interactions were taken into account in order to get a

识别热量限制标记物和热量限制模拟物[发明专利]

专利名称：识别热量限制标记物和热量限制模拟物
专利类型：发明专利
发明人：A·玛斯塔咯迪斯,S·伍德,T·A·波拉,J·L·巴杰,R·温德鲁奇,J·昌
申请号：CN201280039802.2
申请日：20120615
公开号：CN103732745A
公开日：
20140416
专利内容由知识产权出版社提供
摘要：通过使动物暴露于CR条件和多个对象组中选择在响应CR条件差异表达的一种或多种基因，可在选定组织中识别热量限制（CR）标记物。

通过将经所述候选化合物处理的动物与经过CR的动物中的基因表达产物的组织水平进行比较，可筛选在被给予动物时可能具有模拟CR效果能力的候选化合物。

申请人：NSE产品公司
地址：美国犹他州
国籍：US
代理机构：北京纪凯知识产权代理有限公司
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陈述物理化学热力学在药学或生物学领域中的研究文献

陈述物理化学热力学在药学或生物学领域中的研究文献热力学在药学和生物学领域中的应用是广泛的，以下是一些探讨热力学在这些领域中的研究文献的例子：1. "Thermodynamics and Kinetics of Drug Binding to Receptors" (药物结合受体的热力学和动力学)，由Born, Jancso和Bohman 于2009年在Current Medicinal Chemistry杂志上发表。

该研究探讨了药物与受体之间的相互作用，并使用热力学方法研究了药物结合和解离的过程。

2. "Thermodynamic Analysis of Protein Folding" (蛋白质折叠的热力学分析)，由Thirumalai和Woodson于2010年在Annual Review of Biophysics杂志上发表。

该研究利用热力学原理研究了蛋白质折叠的过程，并解释了蛋白质折叠的稳定性和动力学特性。

3. "Thermodynamics of Lipid Membrane Interactions with Drugs" (药物与脂质膜相互作用的热力学)，由Boggs于2009年在Biochimica et Biophysica Acta杂志上发表。

该研究探讨了药物与细胞脂质膜之间的相互作用，并使用热力学方法研究了这些相互作用的热力学特征。

4. "Thermodynamics of Enzyme-Catalyzed Reactions" (酶催化反应的热力学)，由Benkovic和Bunville于2018年在Annual Review of Biochemistry杂志上发表。

该研究利用热力学原理研究了酶催化反应的动力学和热力学特征，并解释了酶催化反应的速率和选择性。

5. "Thermodynamics of Drug-Target Interactions" (药物-靶标相互作用的热力学)，由Mobley和Dill于2009年在Annual Review of Biophysics杂志上发表。

化学反应速率常数的温度依赖性研究

化学反应速率常数的温度依赖性研究化学反应速率是描述化学反应进行快慢的一个重要指标，而反应速率常数则是描述反应速率大小的参数。

在研究化学反应速率常数的温度依赖性时，我们需要了解温度对反应速率的影响。

温度对反应速率的影响可由阿伦尼乌斯方程来描述，即Arrhenius方程：k = A * e^(-Ea/RT)其中，k是反应速率常数，A是指前因子，Ea是活化能，R是气体常数，T是反应温度。

Arrhenius方程表明，反应速率常数k与温度T呈指数关系，即随着温度的升高，反应速率常数k也会增大。

为了研究化学反应速率常数的温度依赖性，我们可以进行一系列实验。

首先，选择一个化学反应，测量在不同温度下的反应速率。

然后，根据Arrhenius方程，利用实验数据拟合出反应速率常数k与温度T之间的关系。

通过拟合得到的Arrhenius方程参数，我们可以进一步分析反应的活化能和前因子。

在实验中，我们需要注意温度的控制和测量。

通常，我们可以使用恒温槽或热电偶来控制和测量反应温度。

同时，为了减少实验误差，需要进行多次重复实验，取平均值。

在进行实验研究时，我们还可以探索其他影响化学反应速率的因素。

例如，反应物浓度、催化剂、溶剂等。

这些因素也可能对反应速率常数的温度依赖性产生影响。

因此，在研究温度对反应速率的影响时，我们需要尽可能地控制这些因素。

化学反应速率常数的温度依赖性研究对于理解化学反应动力学和反应机理具有重要意义。

通过研究反应速率常数与温度的关系，我们可以了解反应过程中的能量变化和反应物分子之间的碰撞频率。

同时，这也有助于我们优化化学反应条件，提高反应效率。

除了实验研究，理论模拟也是研究化学反应速率常数的温度依赖性的重要手段。

通过量子化学计算和分子动力学模拟，我们可以预测反应速率常数与温度的关系，并探索反应过程中的分子动力学细节。

总之，化学反应速率常数的温度依赖性研究是一个复杂而有意义的课题。

通过实验和理论研究，我们可以深入了解温度对反应速率的影响机制，为化学反应的控制和优化提供理论依据。

用于基因治疗的高温诱导表达载体及其使用方法[发明专利]

专利名称：用于基因治疗的高温诱导表达载体及其使用方法专利类型：发明专利
发明人：汤姆·昌,尤金·W·格尔纳,大卫·T·哈里斯,伊万·赫什申请号：CN98812752.0
申请日：19981103
公开号：CN1299411A
公开日：
20010613
专利内容由知识产权出版社提供
摘要：本发明提供了在靶细胞中转基因的表达的方法和组合物。

提供了使用可诱导扩增系统来驱动治疗基因或其它所关注的哺乳动物宿主细胞的基因的表达构建体以及相应的方法。

在生理性条件下的高层次上的转基因的可诱导表达来自于相对于宿主细胞的基础温度的高温条件下的诱导。

申请人：亚利桑那董事会(代表亚利桑那大学)
地址：美国亚利桑那州
国籍：US
代理机构：北京康信知识产权代理有限责任公司
代理人：余刚
更多信息请下载全文后查看。

等温滴定量热法

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ITC法测量结合/解离常数
ITC可以直接测量焓变△H，结合常数Ka，而不对反应体系产生影响，也不引 12 Page 12 入修饰基团，因此测得的结果更加可信
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作用机理研究与分析开发
（△G）与总的结合亲和力直接相，但不能了解结合机理。
等温滴定量热法
(Isothermal Titration Calorimetry, ITC)
翟丽婷 2011-10-13
Isothermal Titration Calorimetry, ITC
等温滴定量热技术（ITC）是一种监测由结合成分的添加而起始的任何
化学反应的热力学技术，即用一种反应物滴定另一种反应物，随着加入滴定剂的数量的变化，测量反应体系温度的变化
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ITC系统是通过细胞反馈网络 CFB来分别测量或者补偿样品和对照由于反应所产生或者吸收的热量。两个硬币状的东西放置在绝热的圆筒中，通过那个细细的管子与外界联通。有两个热量检测装置。一个用来检测两个样品之间的热量差，另一个检测对照和环境的热量差。当样品中发生化学反应的时候，释放或者吸收热量，因此样品和对照的温度差会通过对样品进行增加或者减少热量而稳定在一个水平，就是baseline。因此那些用来维持Δ T1=常数的热量就被系统检 7 Page 7 测画作曲线。
ITC提供了（△G）以及（△H）和（△S），产生了结合机理的真实图像。
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ITC：用生物相关模型系统架起桥梁
ITC的关键优势之一是创建生物相关实验的独特能力。再没有其他技术能提供完全无标记且液相的分析环境，同时无需靶点高分子或配体的固定。ITC的应用在相关模型生物系统的建立和验证中起了重要的作用。

tm磷脂相变温度

tm磷脂相变温度TM磷脂相变温度是指磷脂分子从一个相态转变为另一个相态所需要的温度。

磷脂是一类重要的生物大分子，在细胞膜的结构和功能中扮演着关键的角色。

研究磷脂相变温度对于了解生物膜的形成、稳定性以及细胞功能的调控具有重要意义。

磷脂分子是由一个极性的磷酸基团和两个非极性的脂肪酸基团组成的。

这种分子结构决定了磷脂能够自组装成为一个双层结构，也就是细胞膜的基本结构。

在这个双层结构中，磷酸基团朝向水相，而脂肪酸基团则朝向内部。

随着温度的升高，磷脂分子的热运动增加，分子之间的相互作用变弱，磷脂分子开始从有序状态转变为无序状态。

这个转变点就是TM 磷脂相变温度，也称为磷脂相变温度。

在低于TM的温度下，磷脂分子形成了一个有序的Gel相。

在这个相态下，磷脂分子紧密堆积，相互之间的运动受限。

这种有序结构赋予了细胞膜良好的稳定性和选择性渗透性。

当温度升高到TM以上时，磷脂分子逐渐转变为液晶相。

在液晶相中，磷脂分子的排列变得比较松散，分子之间的运动变得自由。

这种无序结构使得细胞膜的流动性增加，也使得细胞膜上的一些功能蛋白更容易进行相互作用和传递信号。

磷脂相变温度的高低对于细胞膜的功能和稳定性有着重要的影响。

过高或过低的TM都会导致细胞膜的破坏和功能异常。

例如，当TM 过高时，细胞膜的流动性增加，可能导致细胞内外物质的不正常交换；当TM过低时，细胞膜的流动性减弱，可能导致细胞内外物质的交流受限。

磷脂相变温度的研究对于生物医学领域具有重要的应用价值。

例如，在药物传递系统中，研究药物在不同温度下的释放行为可以通过调控TM磷脂相变温度来实现。

此外，还可以利用TM磷脂相变温度来设计新型的细胞膜材料，用于细胞培养、组织工程等领域。

磷脂相变温度是研究细胞膜结构和功能的重要参数。

通过研究TM 磷脂相变温度，我们可以更好地理解细胞膜的特性和行为，为生物医学领域的应用开发提供理论基础和技术支持。

西医综合知识考点：核酸相关名词注释

核酸相关名词注释
1、DNA变性
在某些理化因素作用下，DNA分子互补碱基对之间的氢键断裂，使DNA双螺旋结构松散，变为单链，即为DNA变性。

2、核酶(ribozyme)
具有催化活性的RNA，即化学本质是核糖核酸RNA，却具有酶
的催化功能。

3、增色效应
变性的DNA，分子两条互补链可完全解开成为两条单链，使得
碱基暴露，260nm 处紫外吸收增强，这种现象称为增色效应。

4、Tm值
即解链温度，DNA的变性从开始解链到完全解链，是在一个相
当窄的温度内完成，在这一范围内，紫外光吸收值达到最大值50%
时的温度称为DNA的解链温度，这一现象和结晶的融解过程类似，
又称融解温度(Tm)。

5、DNA超螺旋(DNA supercoil)
DNA双螺旋本身进一步盘绕称超螺旋。

超螺旋有正超螺旋和负
超螺旋两种。

当盘旋方向与DNA双螺旋方向相同时，其超螺旋结构
为正超螺旋，反之则为负超螺旋，负超螺旋的存在对于转录和复制
都是必要的。

6、hnDNA
即核不均一RNA，是mRNA的前体。

7、DNA复性
DNA的复性指变性DNA 在适当条件下，二条互补链全部或部分
恢复到天然双螺旋结构的现象，它是变性的一种逆转过程。

高分子物理重要知识点

高分子物理重要知识点(总43页)--本页仅作为文档封面，使用时请直接删除即可----内页可以根据需求调整合适字体及大小--高分子物理重要知识点第一章高分子链的结构高分子结构的特点和内容高分子与低分子的区别在于前者相对分子质量很高，通常将相对分子质量高于约1万的称为高分子，相对分子质量低于约1000的称为低分子。

相对分子质量介于高分子和低分子之间的称为低聚物（又名齐聚物）。

一般高聚物的相对分子质量为104~106，相对分子质量大于这个范围的又称为超高相对分子质量聚合物。

英文中“高分子”或“高分子化合物”主要有两个词，即polymers和Macromolecules。

前者又可译作聚合物或高聚物；后者又可译作大分子。

这两个词虽然常混用，但仍有一定区别，前者通常是指有一定重复单元的合成产物，一般不包括天然高分子，而后者指相对分子质量很大的一类化合物，它包括天然和合成高分子，也包括无一定重复单元的复杂大分子。

与低分子相比，高分子化合物的主要结构特点是：（1）相对分子质量大，由很大数目的结构单元组成，相对分子质量往往存在着分布；（2）主链有一定的内旋自由度使分子链弯曲而具有柔顺性；（3）高分子结构不均一，分子间相互作用力大；（4）晶态有序性较差，但非晶态却具有一定的有序性。

（5）要使高聚物加工成为有用的材料，需加入填料、各种助剂、色料等。

高分子的结构是非常复杂的，整个高分子结构是由不同层次所组成的，可分为以下三个主要结构层次（见表1－1）：表1-1高分子的结构层次及其研究内容由于高分子结构的如上特点，使高分子具有如下基本性质：比重小，比强度高，弹性，可塑性，耐磨性，绝缘性，耐腐蚀性，抗射线。

此外，高分子不能气化，常难溶，粘度大等特性也与结构特点密切相关。

高分子链的近程结构高分子链的化学结构可分为四类：（1）碳链高分子，主链全是碳以共价键相连：不易水解（2）杂链高分子，主链除了碳还有氧、氮、硫等杂原子：由缩聚或开环得到，因主链由极性而易水解、醇解或酸解（3）元素有机高分子，主链上全没有碳：具有无机物的热稳定性及有机物的弹性和塑性（4）梯形和螺旋形高分子：具有高热稳定性由单体通过聚合反应连接而成的链状分子，称为高分子链。