SYNTHESIS AND CHARACTERIZATION OF AMPHIPHILIC GRAFT COPOLYMER CONTAINING MICROPHASE SEPARAT
Al-MCM-41分子筛的制备及其催化合成聚甲氧基二甲醚
2021 年第50 卷第 2 期石油化工PETROCHEMICAL TECHNOLOGY·103·研究与开发DOI ：10.3969/j.issn.1000-8144.2021.02.001［收稿日期］2020-08-04；［修改稿日期］2020-11-06。
［作者简介］李国斌（1995—），男，甘肃省庆阳市人，硕士生，电话 183********，电邮 291988543@ 。
联系人：陈立宇，电话187********，电邮 chenly@ 。
Al-MCM-41分子筛的制备及其催化合成聚甲氧基二甲醚李国斌，徐彩霞，陈立宇（西北大学 化工学院，陕西 西安 710069）［摘要］采用水热合成法制备了不同Al 含量的Al -MCM -41介孔分子筛，考察了分子筛催化甲醇和多聚甲醛合成聚甲氧基二甲醚（PODE n ，n 为聚合度）的性能；采用XRD 、FTIR 、N 2吸附-脱附、ICP -OES 、SEM 、NH 3-TPD 等方法分析了分子筛的孔结构和酸性质对产物分布的影响，并对PODE n 的合成工艺条件进行了优化。
实验结果表明，制备的Al -MCM -41分子筛具有二维六方有序介孔结构；Al 的掺入导致分子筛的比表面积、孔体积和孔径出现不同程度的减小，但有效提高了分子筛的中强酸量，进而促进高聚合度产物的生成；硅铝比为40的Al -MCM -41（40）分子筛的催化性能最优。
PODE n 最佳合成条件为：135 ℃、5 h 、甲醇与多聚甲醛的摩尔比为1.5、催化剂的用量为2%（w ），在此条件下，甲醇转化率达74.5%，PODE 3～5选择性达31.3%。
Al -MCM -41（40）分子筛重复使用5次仍具有较好的催化活性。
［关键词］MCM -41分子筛；聚甲氧基二甲醚；铝改性；酸催化；多聚甲醛［文章编号］1000-8144（2021）02-0103-09 ［中图分类号］TQ 426.94 ［文献标志码］APreparation of Al -MCM -41 zeolite and its catalytic performance in the synthesisof polymethoxy dimethyl etherLi Guobin ，Xu Caixia ，Chen Liyu（School of Chemical Engineering ，Northwest University ，Xi ’an Shaanxi 710069，China ）［Abstract ］Al-MCM-41 mesoporous zeolite with different Al contents were synthesized by the hydrothermal method. The catalytic performances of Al-MCM-41 zeolite in the synthesis of polyoxymethylene dimethyl ethers(PODE n ，n represents degree of polymerization) with methanol and paraformaldehyde were investigated. XRD ，FTIR ，N 2 adsorption-desorption ，ICP-OES ，SEM ，and NH 3-TPD techniques were used to analyze the pore structure and acid properties of Al-MCM-41，whose influence on the product distribution was discussed. The synthesis process conditions of PODE n were further optimized. The results show that the prepared Al-MCM-41 has an ordered two-dimensional hexagonal mesoporous structure. The doping of Al causes the specific surface area ，pore volume and pore size of the zeolite decrease ，while effectively increases the amount of medium-strong acid in zeolite which promotes the formation of high polymerization products. When the molar ratio of Si/Al is 40，the Al-MCM-41(40) zeolite shows the best catalytic performance. The optimal synthesis condition for PODE n is that the reaction temperature being 135 ℃，reaction time being 5 h ，the ratio molar of methanol to paraformaldehyde being 1.5，and the amount of catalyst being 2%(w ). Under the optimal condition ，the conversion of methanol reaches 74.5% and the selectivity to PODE 3-5 is up to 31.3%. Al-MCM-41(40) zeolite catalyst exhibited good catalytic activity after being reused for 5 times.［Keywords ］MCM-41 zeolite ；polymethoxy dimethyl ether ；alumina modification ；acid catalysis ；paraformaldehyde2021 年第50 卷石油化工PETROCHEMICAL TECHNOLOGY·104·聚甲氧基二甲醚（PODE n ，n 为聚合度，1≤n ≤8）作为甲醇产业下游产物具有较高的含氧量（42%～51%（w ））和十六烷值（大于60），物性与柴油相似，是一种新型绿色柴油添加剂。
amplab原理
amplab原理The amplab principle is a concept that involves the use of technology and algorithms to enhance the performance of computer systems. Amplab原理是涉及利用技术和算法来增强计算机系统性能的概念。
This principle is crucial in the field of computer science and has a significant impact on the development of new technologies and applications. 这个原理对计算机科学领域至关重要，并对新技术和应用的开发产生了重大影响。
One perspective on the amplab principle is that it enables the efficient processing and analysis of large datasets. 一个关于amplab 原理的观点是它能够高效处理和分析大型数据集。
This is particularly important in the era of big data, where organizations and researchers are dealing with massive amounts of information that need to be managed and analyzed effectively. 这在大数据时代尤为重要，组织和研究人员需要有效地处理和分析大量信息。
Another perspective is the role of the amplab principle in advancing machine learning and artificial intelligence. 另一个视角是amplab原理在推动机器学习和人工智能方面的作用。
Synthesis and characterization of novel systems fo
专利内容由知识产权出版社提供
专利名称：Synthesis and characterization of novel systems for guidance and vectorization of molecules of therapeutic interest towards target cells
发明人：Pascal Dumy,Marie-Christine Favrot,Didier Boturyn,Jean-Luc Coll
申请号：US10528320 申请日：20030919 公开号：US07531622B2 公开日：20090512
摘要：A method for preparing a grafted homodetic cyclopeptide forming a framework that defines a grafted upper face and grafted lower face, including synthesizing a linear peptide from modified or unmodified amino acids, some of which carry orthogonal protective groups; intramolecular cyclizing the resulting protetuting some or all of orthogonal protective groups with a protected precursor; and grafting at least one molecule of interest onto one and/or the other face of the framework via an oxime bond.
堆肥腐殖酸形成及其电化学活性
补充活性腐殖酸ꎬ防止腐殖酸因修复氧化还原过程导致降解后只能作为碳源.
关键词: 垃圾堆肥ꎻ 腐殖酸ꎻ 氨基酸ꎻ 电化学
中图分类号: Ｘ７０５ 文章编号: １００１￣６９２９(２０２１)１２￣２９８０￣０９
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ｌｉｇｎｏｃｅｌｌｕｌｏｓｅꎬ ｂｕｔ ｔｈｅ ｃｏｍｐｏｓｉｔｉｏｎ ｏｆ ａｍｉｎｏ ａｃｉｄｓ ｉｎ ｔｈｅ ｃｏｍｐｏｓｔｉｎｇ ｐｒｏｃｅｓｓ ａｎｄ ｔｈｅ ｒｅａｃｔｉｏｎ ｃｈａｒａｃｔｅｒｉｓｔｉｃｓ ｂｅｔｗｅｅｎ ｈｕｍｉｃ ａｃｉｄｓ ｗｉｔｈ
ｌｉｇｎｏｃｅｌｌｕｌｏｓｅ ａｒｅ ｓｔｉｌｌ ｎｏｔ ｃｌｅａｒ. Ｈｅｎｃｅꎬ ｔｈｅ ｅｆｆｅｃｔ ｏｆ ｒｅｄｏｘ ｐｒｏｃｅｓｓ ｏｎ ｔｈｅ ｆｏｒｍａｔｉｏｎ ｏｆ ｃｏｍｐｏｓｔｉｎｇ ｈｕｍｉｃ ａｃｉｄｓ ｃａｎｎｏｔ ｂｅ ｅｖａｌｕａｔｅｄ. Ｉｎ
增加以及垃圾分类的有效推进ꎬ城市生活垃圾中易腐
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Synthesis and characterization of carbon-doped titania as an artificial solar light photocatalyst
Synthesis and characterization of carbon-doped titania as an artificial solar light sensitive photocatalystYuanzhi Lia,b,Doo-Sun Hwang a ,Nam Hee Lee a ,Sun-Jae Kima,*aSejong Advanced Institute of Nano Technologies,#98Gunja-Dong,Gwangjin-Gu,Sejong University,Seoul 143-747,KoreabDepartment of Chemistry,China Three Gorges University,8College road,Yichang,Hubei 4430002,PR ChinaReceived 1December 2004;in final form 4January 2005AbstractThe carbon-doped titania with high surface area was prepared by temperature-programmed carbonization of K-contained ana-tase titania under a flow of cyclohexane.This carbon-doped titania has much better photocatalytic activity for gas-phase photo-oxi-dation of benzene under irradiation of artificial solar light than pure titania.The visible light photocatalytic activity is ascribed to the presence of oxygen vacancy states because of the formation of Ti 3+species between the valence and the conduction bands in the TiO 2band structure.The co-existence of K and carbonaceous species together stabilize Ti 3+species and the oxygen vacancy state in the as-synthesized carbon-doped titania.Ó2005Elsevier B.V.All rights reserved.Titania is well known as a cheap,nontoxic,efficient photocatalyst for the detoxication of air and water pol-lutants.However,it is activated only under UV light irradiation because of its large band gap (3.2eV).Be-cause only 3%of the solar spectrum has wavelengths shorter than 400nm,it is very important and challeng-ing to develop efficient visible light sensitive photocata-lysts by the modification of titania.Several attempts have been made to narrow the band gap energy by tran-sition metal doping [1–3],but these metal-doped photo-catalysts have been shown to suffer from thermal instability,and metal centers act as electron traps,which reduce the photocatalytic efficiency.Recently,the mod-ification of titania by nonmetals (e.g.S,N,C,B)receive much attention as the incorporation of these nonmetals into titania could efficiently extend photo-response from UV (ultra-violet)to visible regions [4–10].Here,we re-port a method of synthesizing carbon-doped titania with a high surface area.It was found that the as-synthesizedcarbon-doped titania showed much better photocata-lytic activity for photo-oxidation of benzene under irra-diation of artificial solar light than undoped titania.The as-synthesized carbon-doped titania was pre-pared by the following procedure.0.10mol TiCl 4(98%TiCl 4,Aldrich)were added slowly drop wise into 200ml portions of distilled water in an ice bath.The ob-tained transparent TiOCl 2aqueous solution was heated rapidly to 100°C,and then kept at this temperature for 10min for hydrolysis of TiOCl 2.The precipitates formed in the solution were filtered,neutralized to pH 8.0by 0.1mol/l KOH aqueous solution,washed thor-oughly with distilled water,and then finally dried at 150°C in air for 24h.The carbon-doped titania was prepared by temperature-programmed carbonization (TPC)of anatase titania in a flow of Ar saturated by cyclohexane at 20°C in a quartz tube reactor.The load-ing of titania was 2g,and the flowing rate of Ar was 500ml (STP)/min.The sample was heated to the car-bonization temperatures between 450and 500°C at a rate of 0.5°C/min and kept at the temperature for 2h.After rapidly cooling to room temperature in a flow of Ar,a grayish sample of titania was obtained.0009-2614/$-see front matter Ó2005Elsevier B.V.All rights reserved.doi:10.1016/j.cplett.2005.01.062*Corresponding author.Fax:+82234083664.E-mail address:sjkim1@sejong.ac.kr (S.-J.Kim)./locate/cplettChemical Physics Letters 404(2005)25–29The crystalline phase of samples was determined by XRD.Before TPC,the obtained titania prepared by hydrolysis of TiOCl2aqueous solution had pure anatase structure.The crystalline phase of anatase sample was almost unchanged even after TPC except for the forma-tion of a small amount of rutile phase infinally obtained carbon-doped pared to pure titania pre-pared by same procedure but replacing cyclohexane sat-urated Ar by air,the carbon doped titania has lower rutile content,indicating that TPC inhibited the trans-formation of anatase to rutile phase.The average crystal size of as-synthesized carbon-doped titania is estimated by the Scherrer formula:L=0.89k/b cos h to be7.6nm. BET surface area measurement showed that the as-syn-thesized carbon-doped titania by TPC at475°C had as high as204m2/g specific surface area,which is impor-tant for improving photocatalytic activity.But the car-bon-doped titania prepared by reported carbon doping method usually had a lower specific surface area and larger crystal size[11,12].Fig.1gives the UV–Vis diffusive reflectance absorp-tion spectra of the pure titania and carbon-doped titania pared to that of the carbon-doped titania, the absorption edge near400nm of the pure titania has a red-shift of20nm,which might be contributed by the higher content of rutile in pure titania than in carbon-doped titania,as rutile has a narrower band gap (3.0eV)than anatase(3.2eV).The as-synthesized pure titania almost has no absorption above400nm.How-ever,the doping of carbon results in obvious absorption of titania up to700nm.This absorption feature suggests that these carbon-doped titania can be activated by visible light.The photocatalytic activity of as-synthesized titania samples for the gas-phase oxidation of benzene was tested on a home-made re-circulating gas-phase photo-reactor with a quartz window,which was connected to the ppbRAE meter(RAE system Inc.)to re-circulate a mixture of benzene and ambient air without additional drying and measure concentration of the volatile organic compounds(VOCs).Artificial solar light with full spec-trum(32W VITA LITE lamp)was used as irradiation source.First,0.7000g titania powder was put into the reactor,then a known amount of benzene was injected in the system under dark.After the adsorption of benzene on titania reached to adsorption equilibrium,artificial solar light was turn on.Fig.2shows the amounts of total volatile organic compounds(VOCs)with the artificial so-lar light irradiation time.Morawski and co-workers[13] prepared carbon-modified titania by heating at the high temperatures of titanium dioxide in an atmosphere of gaseous n-hexane.They found that carbon-modified titania had catalytic photoactivity slightly lower than that of TiO2without carbon deposition.In our experi-ment of preparing anatase TiO2by hydrolysis of TiOCl2 solution,the precipitate was neutralized to pH8.0by 0.1mol/l KOH aqueous solution.When we did not use KOH solution to neutralize the titania precipitate and just washed thoroughly the titania precipitate with dis-tilled water.Then,we use this titania without neutraliza-tion by KOH solution to prepare the carbon-doped titania by TPC.It was found that this carbon-doped titania has almost similar photocatalytic activity for the gas-phase photo-oxidation of benzene to the un-doped titania prepared by the same procedure but replacing cyclohexane saturated Ar by air.This result is similar to the result reported by Morawski et al.How-ever,the as-synthesized carbon-doped titania,which was prepared by TPC of anatase titania with neutralization by KOH solution,have much better photoactivity for the gas-phase photo-oxidation of benzene than the un-doped titania as well as Degussa P25titania,a bench-marking photocatalyst.This result shows that the neutralization of titania by KOH solution plays very important role in the photocatlytic activity of thefinally obtained carbon-doped titania,and doping a proper26Y.Li et al./Chemical Physics Letters404(2005)25–29amount of carbon into the KOH neutralized titania by our method leads to the obvious enhancement of its photoactivity.Our experiment shows that thefinal carbonization temperature has an important effect on the photoactiv-ity,and the optimum carbonization temperature is be-tween475and500°C.The photocatalytic activity of the as-synthesized carbon-doped titania is unchanged after several successive cycles of photocatalytic tests un-der artificial light irradiation,indicating the stability of the catalysts after photolysis.Asahi et al.[5]made a theoretical calculation of the densities of states(DOSs)of the substitutional doping of C,N,F,P,or S for O in the anatase TiO2crystal by the full-potential linearized augmented plane wave in the framework of the local density approximation (LDA).They thought that the substitutional doping of N or S was the most effective because its p states contrib-ute to the band gap narrowing by mixing with O2p states,but the states introduced by C and P are too deep in the gap to satisfy one of the requirements for visible light sensitive photocatalyst.However,previous works [11,12,14]and our experiment show that the carbon-doped titania has visible light photocatalytic activity. Therefore,we must try tofind the reason why as-synthe-sized carbon-doped titania has visible light photocata-lytic activity.To investigate the carbon states in the photocatalyst, C1s core levels were measured by X-ray photoemission spectroscopy(XPS),as shown in Fig.3a.There are two XPS peaks at284.6,288.2eV for the as-synthesized carbon-doped titania,but it was confirmed that there was only one peak at284.6eV for pure titania even though it is not shown here.Obviously the peak at 284.6eV arises from adventitious elemental carbon. Hashimoto and co-workers[11]prepared carbon-doped titania by oxidizing TiC,and observed C1s XPS peak with much lower binding energy(281.8eV).They as-signed this C1s XPS peak to Ti–C bond in carbon-doped anatase titania by substituting some of the lattice oxygen atom by carbon.Khan et al.[12]synthesized carbon-modified rutile titania by controlledflame pyrolysis of Ti metal,and thought that the carbon substituted for some of the lattice oxygen atoms.However,Sakthivel and Kisch[14]prepared carbon-modified titania by hydrolysis of titanium tetrachloride with tetrabutylam-monium hydroxide followed by calcinations at400°C, and observed the two kinds of carbonate species with binding energies of287.5and288.5eV.These resultssuggest that the preparation method plays an important role in determining the carbon oxidation state in car-bon-modified titania:both substitution of the lattice oxygen in the titania and the formation of carbonate species in titania lead to the narrowing of the band gap infinal obtained carbon-doped titania.Our result is similar to that of Sakthivel and Kisch,but the carbon-doped titania prepared by our method only has one peak nearby at288.2eV,indicating the presence of only one kind of carbonate species.Therefore,our result does not contradict the theoretical expectation of Asahi et al.because the carbon exists in form of carbonate, not by substituting the oxygen of the anatase in the as-synthesized carbon-doped titania.The sensitivity ofY.Li et al./Chemical Physics Letters404(2005)25–2927the as-synthesized carbon-doped titania to visible light maybe arises from other reason.The surface carbon concentration in our sample was estimated by XPS to be7.3%.The XPS spectral of Ti2p region were also shown(Fig.3b).The XPS spectra of Ti2p3/2in the car-bon-doped titania can befitted as one peak at457.8eV. Compared to the binding energy of Ti4+in pure anatase titania(458.6eV),there is a red-shift of0.8eV for the carbon-doped titania,which suggests that Ti3+species was formed in the carbon-doped titania[15].In our experiment of preparing anatase TiO2,the precipitate was neutralized to pH8.0by0.1mol/l KOH aqueous solution.K was also detected by XPS in thefinally ob-tained carbon-doped titania prepared from this KOH neutralized titania.The XPS spectral of K2p region were also shown(Fig.3c).The XPS spectra of K2p3/2in the carbon-doped titania can befitted as one peak at 292.5eV,which could be assigned to K+.The surface K concentration in our sample was estimated by XPS to be13.3%.Fig.4shows EPR spectra of as-synthesized doped titania,recorded at77K and ambient temperature un-der dark.The XPS results show the presence of Ti3+ in the as-synthesized carbon-doped titania.It can be seen from Fig.4that Ti3+is also detected by EPR at low temperature(77K).Moreover,there are observed two kinds of Ti3+in the as-synthesized carbon-doped titania.The signal at g^=1.9709,g i=1.9482is assigned to surface Ti3+[16,17],and the signal at g=1.9190is as-signed to vacancy-stabilized Ti3+in the lattice sites or similar center in the subsurface layer of titania[18,19]. At ambient temperature,the Ti3+EPR signal disap-pears,but the strong symmetric signal at g=2.0055still exists,and no EPR signal was detected for pure anatase titania.Moreover,our experiment showed that the used carbon-doped titania still had a strong EPR signal at g=2.0055after experienced photocatalytic test.Serwicka[20]observed a broad signal assigned to Ti3+ ions at g=1.96and a sharp signal at g=2.003on the vacuum-reduced TiO2at673–773K.They attributed the latter signal to a bulk defect,probably an electron trapped on an oxygen vacancy.Nakamura et al.[21]re-ported that the symmetrical and sharp EPR signal at g=2.004detected on plasma-treated TiO2arose from the electron trapped on the oxygen vacancy.The pres-ence of Ti3+in the as-synthesized carbon-doped titania implies that there must be some change for oxygen spe-cies localized near Ti3+in the carbon-doped titania to satisfy the requirement of charge equilibrium,which is further confirmed by the EPR proof of the existence of vacancy-stabilized Ti3+in the as-synthesized carbon doped bined with the reported assignment for the EPR signal,the signal at g=2.0055newly ob-served here for the as-synthesized carbon-doped titania can be assigned to the electron trapped on the oxygen vacancy.It was reported that reducing TiO2introduces localized oxygen vacancy states located at0.75–1.18eV below the conduction band edge of TiO2[22],which re-sults in sensitivity of the reduced TiO x photocatalyst to visible light.So,for titania containing localized oxygen vacancy,the band gap between valence band and local-ized oxygen vacancy state is 2.45–2.02eV.Our UV experiments showed that the carbon-doped titania has an obvious absorption up to700nm(mainly in the re-gion of450–610nm(2.74–2.02eV))as shown in Fig.1, which further confirms that localized oxygen vacancy states actually exist in the as-synthesized carbon-doped titania and the existence of localized oxygen vacancy states results in the sensitivity of the as-synthesized car-bon-doped titania photocatalyst to visible light.Based on our results of UV,XPS and EPR,it is concluded that the presence of Ti3+species produced in the process of carbon doping of the K-contained titania leads to the formation of oxygen vacancy state(O t.Ti3+)in the as-synthesized carbon-doped titania between the valence and the conduction bands in the TiO2band structure, which results in the sensitivity of the as-synthesized car-bon-doped titania to visible light and its high photocat-alytic activity under irradiation of artificial solar light.It was proved by our photocatalytic experiment that the oxygen vacancy state in the as-synthesized carbon-doped titania had good stability because its photocata-lytic activity was unchanged after several successive cycles of photocatalytic test under artificial light irradiation.We think that the co-existence of K and carbonaceous species together stabilize Ti3+species and the oxygen vacancy state in the as-synthesized carbon-doped titania.In summary,the carbon-doped titania with high sur-face area and good crystallinity was prepared by temper-ature-programmed carbonization of nano anatase titania withfinal carbonization temperature of475°C under aflow of cyclohexane.This carbon-doped titania28Y.Li et al./Chemical Physics Letters404(2005)25–29showed an obvious absorption of titania up to700nm, and had much better photocatalytic activity for gas-phase photo-oxidation of benzene under irradiation of artificial solar light than pure titania.The visible light photocatalytic activity is ascribed to the presence of oxy-gen vacancy state because of the formation of Ti3+spe-cies in the as-synthesized carbon-doped titania between the valence and the conduction bands in the TiO2band structure,which results in sensitivity of the as-synthe-sized carbon-doped titania to the visible light. AcknowledgmentsThe authors are grateful to Basic Research Program of Korea Science and Engineering Foundation(Grant No.R01-2002-000-00338)forfinancial support. References[1]H.Kisch,L.Zang, nge,W.F.Maier, C.Antonius, D.Meissner,Angew.Chem.,Int.Ed.37(1998)3034.[2]W.Macyk,H.Kisch,Chem.Eur.J.7(2001)1862;C.Wang,D.W.Bahnemann,J.K.Dohrmann,mun.16(2000)1539.[3]H.Yamashita,M.Honda,M.Harada,Y.Ichihashi,M.Anpo,T.Hirao,N.Itoh,N.Iwamoto,J.Phys.Chem.B102(1998) 10707.[4]T.Umebayashi,T.Yamaki,H.Itoh,K.Asai,Appl.Phys.Lett.81(3)(2002)454.[5]R.Asahi,T.Ohwaki,K.Aoki,Y.Taga,Science293(2001)269.[6]C.Burda,Y.Lou,X.Chen,A.C.S.Samia,J.Stout,J.L.Gole,Nano Lett.3(8)(2003)1049.[7]H.Irie,Y.Watanabe,K.Hashimoto,J.Phys.Chem.B107(2003)5483.[8]J.L.Gole,J.D.Stout,C.Burda,Y.Lou,X.Chen,J.Phys.Chem.B108(2004)1230.[9]T.Lindgren,J.M.Mwabora,E.Avendano,J.Jonsson,A.Hoel,C.Granqvist,S.Lindquist,J.Phys.Chem.B107(2003)5709.[10]W.Zhao,W.Ma,C.Chen,J.Zhao,Z.Shuai,J.Am.Chem.Soc.126(2004)4782.[11]H.Irie,Y.Watanabe,K.Hashimoto,Chem.Lett.32(8)(2003)772.[12]S.U.M.Khan,M.Al-shahry,W.B.Ingler Jr.,Science297(2002)2243.[13]M.Janus,B.Tryba,M.Inagaki,A.W.Morawski,Appl.Catal.B52(2004)61.[14]S.Sakthivel,H.Kisch,Angew.Chem.,Int.Ed.42(2003)4908.[15]X.Y.Du,Y.Wang,Y.Y.Mu,L.L.Gui,P.Wang,Y.Q.Tang,Chem.Mater.14(2002)3953.[16]Y.Z.Li,Y.N.Fan,H.P.Yang,B.L.Xu,L.Y.Feng,M.F.Yang,Y.Chen,Chem.Phys.Lett.372(2003)160.[17]L.Bonneviot,G.L.Haller,J.Catal.113(1988)96.[18]T.Huizinga,R.Prins,J.Phys.Chem.85(1981)2156.[19]S.A.Fairhurst, A.D.Inglis,Y.Le Page,J.R.Morton,K.F.Preston,Chem.Phys.Lett.95(1983)444.[20]E.Serwicka,Colloid.Surf.13(1985)287.[21]I.Nakamura,N.Negishi,S.Kutsuna,T.Ihara,S.Sugihara,K.Takeuchi,J.Mol.Catal.A161(2000)205.[22]D.C.Cronemeyer,Phys.Rev.113(1959)1222.Y.Li et al./Chemical Physics Letters404(2005)25–2929。
有机合成逆合成分析法与有机反应概览
• 在非质子性极性溶剂中，亲核试剂亲核性的增 加比碱性增加显著
• 电荷的离域使亲核试剂碱性减弱的趋势大于亲 核性减弱，因此，丙二酸酯碳负离子的碱性和 亲核性均较EtO2CC(H)(R)-小，但亲核性与碱 性的比值前者较后者大
• 亲核试剂进攻原子与另一含有孤对电子的原子 相连（HOO-；NH2NH2），亲核性增强， HOO-＞ HO-
（1）一个原子提供两个电子作为共享电子（电 子对），即通过一个碳亲核体Nu和一个碳亲电体 （E）的离子型（极性）结合形成碳-碳
（C+ + C- C-C,大多数情况是Cδ+ + Cδ- C-C ） （2）每个碳原子贡献一个电子以形成共享的电子
对，也就是说通过两个自由基的结合形成C-C键。
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n Pr H C
Ph OH
1.苯基丁醇的逆合成分析之二。C-H的切断
FGI n Pr H
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n Pr δ+ Ph + C
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n Pr δ+ Ph C
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试剂（ 酰氯） 格氏试剂
第22页/共67页
1.1.2.2 指导切断的指南
X
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X= OR, -NHR, -SR, etc
CX
第33页/共67页
内酯具有桃香味，是香水的一种成分，其逆合成 分析可从内酯C-O键切断入手
O
HO COOH
O
O+ HOOC
第34页/共67页
按上述逆合成分析的合成路线为：
5′位氨基修饰的核苷化合物的合成
核苷或核苷酸类似物在体 内可以作为 “ 假底 物” 干扰或 直接作 ， 用 于核酸 的代谢 ， 阻断蛋 白质 、 核酸 的生物合成 ， 而起 到抑 制 从
病毒复制 以及肿瘤 细胞生长 的作用 ， 为化疗 中极具吸 引力 的 成 途径 ， 作为重要的抗肿 瘤 、 病毒 类药 物及药 物 中间体”Ｉ ， 抗 ２ 对 天然核苷 的结构修饰 和改造来增强 药物活性的课题 引起 了化学 工作者 的广泛关注和极大兴趣 。除 了大量的对碱基结构 的改造 工作外 Ｊ近年来 ， ， 对糖 环的改 造也成 了关注 的热点 。对 于 核糖而言 ， 结构改造主要从糖环三个羟基 的选 择性 保护开始 Ｊ ，
１ 实验 及 原 理
１ １ 实验 试剂 与仪器 ．
ＨＮ ＭＲ和” ＭＲ经 Ａ Ａ Ｃ ４ ０型核 磁共 振仪 （Ｏ ＣＮ Ｖ Ｎ Ｅ一 Ｏ ・０ ４ ＭＨ ， Ｏ ｚＭｅ Ｄ为溶剂 ，ＭＳ为内标 ） Ｔ 测定 ， 质谱（ ） Ｖ ７ ７ Ｅ ＭＳ 经 Ｇ一 ０ ０ （Ａ ） Ｆ Ｂ 测定。本文所用试剂和溶剂均 为国产或进 口分 析纯或化 学纯 ， 无水溶剂 均按 照相应常规 方法 处理。柱层析 硅胶 （ ０ ２ ０— ３０目） ０ 及薄层层析硅胶 （ Ｆ ） Ｇ 由青岛海洋化工厂生产 。
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Synthesis and Characterization of PEG Dimethacrylates and__Their Hydrogels
Synthesis and Characterization of PEG Dimethacrylates andTheir HydrogelsSheng Lin-Gibson,*,†Sidi Bencherif,†James A.Cooper,†Stephanie J.Wetzel,†Joseph M.Antonucci,†Brandon M.Vogel,†Ferenc Horkay,‡and Newell R.Washburn†Polymers Division,National Institute of Science and Technology,Gaithersburg,Maryland20899-8543,and Section on Tissue Biophysics and Biomimetics,Laboratory of Integrative and Medical Biophysics,NICHD, National Institutes of Health,Bethesda,Maryland20892Received February26,2004Facile synthesis and detailed characterization of photopolymerizable and biocompatible poly(ethylene glycol) dimethacrylates(PEGDM)and poly(ethylene glycol)urethane-dimethacrylates(PEGUDM)are described. Poly(ethylene glycol)s of various molecular masses(M n)1000to8000g/mol)were reacted with methacrylic anhydride or with2-isocyanatoethyl methacrylate to form PEGDMs and PEGUDMs,respectively.PEGDMs were also prepared by a microwave-assisted route to achieve fast reaction conversions under solvent free bined analyses of1H NMR and MALDI-TOF MS confirmed the formation of prepolymers of high purity and narrow mass distribution(PD<1.02).Aqueous solutions of the PEGDMs and PEGUDMs (10%and20%by mass fraction)were photopolymerized to yield hydrogels.Bovine chondrocytes,seeded in the hydrogels,were used to assess the biocompatibility.Preliminary rheology and uniaxial compression measurements showed varied mechanical response,and biocompatibility studies showed that cells are completely viable in both types of hydrogels after two weeks.IntroductionHydrogels produced by photopolymerization have been investigated extensively as biomaterials in applications such as scaffolds for tissue engineering,drug delivery carriers,in the prevention of thrombosis,post-operative adhesion forma-tion,and as coatings for biosensors.1The photopolymeriza-tion process allows the hydrogel to be generated in vitro or in vivo from a low viscosity solution of monomer,oligomer, or low molecular mass polymer(macromer)by a free radical pathway in a minimally invasive manner.The chemical cross-linking results in hydrogels that contain a high water content yet possess mechanical properties similar to those of soft tissues.Another advantage of hydrogels is their high permeability to oxygen,nutrients,and other water-soluble metabolites,making them particularly attractive as scaffolds in tissue engineering applications.Although hydrogels have been studied as potential materi-als for bone,tendon,and nerve regeneration,it is cartilage tissue engineering that has shown the most promise.Chon-drocytes encapsulated in hydrogels retain their native form, and over time can generate native cartilage tissue.The use of photopolymerized hydrogels as opposed to natural physical gels such as alginate also allows for the material properties to be more easily adjusted.For example,a typical approach to control the hydrogel mechanical properties is to tailor the network cross-link density.This can be achieved by adjusting the molecular mass of the macromer or by varying the mass percent of macromer in the solutions.The cross-link density in fully cross-linked networks is directly proportional to the gel modulus and inversely proportional to the swelling.These are important considerations for tissue engineering in which the former affects transport properties and the latter deter-mines the materials functional practicality and influences cell behavior.In drug delivery applications,the pore or mesh size can be adjusted to control the drug release rate by varying the content,density,and length of the cross-linking groups.Several types of photopolymerizable hydrogels have been investigated for use as biomaterials.These include poly-(ethylene glycol)(PEG)acrylate derivatives,PEG meth-acrylate derivatives,poly(propylene fumarate-co-ethylene glycol)2and oligo(poly(ethylene glycol)fumarate)3that contains cross-linkable sites in the polymer backbone,poly-(vinyl alcohol)derivatives,4modified polysaccharides such as those from hyaluronic acid,and dextran methacrylates. We are particularly interested in PEG dimethacrylates (PEGDM)and similar PEGDM derivatives as model systems because PEG alone is bio-inert but can be easily modified to become bioactive.5Cross-linking by dimethacrylates have been shown to be biocompatible with the unreacted dimeth-acrylates having relatively low cytotoxicity.6,7In addition, PEGDMs and their copolymers and derivatives have been successfully used by several groups both in vitro and in vivo as scaffold materials.8There is a general consensus that the material properties and external stimulation strongly affect the cell response. The importance of PEGDM hydrogel cross-link density (controlled by PEGDM mass fraction in solution)on me-*To whom correspondence should be addressed.E-mail:slgibson@.†National Institute of Science and Technology.‡National Institutes of Health.1280Biomacromolecules2004,5,1280-128710.1021/bm0498777CCC:$27.50©2004American Chemical SocietyPublished on Web04/21/2004chanical properties and on the chondrocytes’ability toproduce cartilaginous tissues has been demonstrated byBryant and Anseth.9In addition,PEGDM co-photopolymer-ized with a degradable macromer,acrylate endcapped poly-(lactic acid)-b-poly(ethylene glycol)-b-poly(lactic acid)in thepresence of chondrocytes shows that biodegradable moietiesin hydrogels have significant effects in tissue generation.Despite the large number of studies currently available,thereis still a lack of a clear understanding of the correlationbetween material properties and cell response.Furthermore,after years of research,the physical properties of hydrogelsare still difficult to predict by theories due to nonidealitiesof the gel formation.These nonidealities include conversiondependent reactivity,cyclization and multiple cross-linking,and defects and nonhomogeneous cross-linking(also knownas spatial gel inhomogeneity).Well-defined model materialsare necessary for the preparation of hydrogels with highreproducibility and easily adjustable properties.We have prepared a series of controlled molecular mass(MM)PEGDMs and poly(ethylene glycol)urethane dimeth-acrylates(PEGUDM)of high purity and low polydispersity.PEGDMs were prepared both in solution and under solventfree conditions via a microwave-assisted route.The syntheticapproaches described herein are particularly straightforward.The dimethacrylate products were characterized by protonnuclear magnetic resonance(1H NMR)and matrix-assistedlaser desorption ionization time-of-flight mass spectrometry(MALDI-TOF MS).PEGDMs and PEGUDMs of differentmolecular masses were photocrosslinked to form hydrogels,and preliminary cell viability studies were conducted.Thematerial structure-property relationships and detailed cellresponse studies will be described in a later paper.Experimental Section15Materials.PEG(MM≈1000(1k)to8000g/mol(8k)),methacrylic anhydride(MA),2-isocyanatoethyl methacrylate(IEM),ethyl ether,and triethylamine(TEA)were purchasedfrom Sigma-Aldrich and used as received.Dichloromethanewas purchased from Sigma-Aldrich and dried over activatedmolecular sieves(4Å)prior to use.Photoinitiator Irgacure2959(I2959)was obtained from Ciba Specialty Chemicalsand used as received.Primary bovine chondrocytes werecultured in growth medium composed of Dulbecco’s modi-fied Eagle medium,10%fetal bovine serum,1%minimumessential medium(GIBCO,Invitrogen Corp),50µg/mL L-ascorbic acid2-phosphate(Sigma),and1%antibiotics (penicillin/streptomycin)(Mediatech,Inc.).Cell viability wasmeasured using Live/Dead Viability/Cytotoxicity Kit(L-3224)purchased from Molecular Probes Inc.Synthesis of PEGDM and PEGUDM.PEGDM andPEGUDM were prepared from the reaction of various PEGsand MA or IEM,respectively.An example of the synthesisof a5k PEGDM is as follows.PEG(5g,≈0.001mol),2.2equiv of MA(0.34g,0.0022mol),and TEA(0.2mL)werereacted in≈15mL of dichloromethane over freshly activatedmolecular sieves(≈3g)for4d at room temperature.Thesolution was filtered over alumina and precipitated into ethylether.The product was filtered and then dried in a vacuumoven overnight at room temperature.Microwave-Assisted Synthesis of PEGDM.PEG(0.2g) and a large excess of MA(up to5-fold excess)were mixed in a capped scintillation vial and placed in a commercial domestic microwave(GE,1100W)for various reaction times ranging from2to10min.Once the vial was cooled to room temperature,approximately2mL of ethyl ether was added and the vial was gently shaken to allow the PEGDM to precipitate.For the1k PEGDM,the vial was placed in a freezer to facilitate the precipitation process.Product was collected by filtration and dried in a vacuum oven. Characterization PEGDM and PEGUDM.High-resolu-tion,270MHz proton NMR spectra were taken on a6.35T JEOL GX270spectrometer manufactured by JEOL,Ltd. (Akishima,Japan).Deuterated chloroform was used as a solvent,and the polymer concentrations were varied between 2.5%and3.0%by mass fraction.All spectra were run at room temperature,15Hz sample spinning,45°tip angle for the observation pulse,and a10s recycle delay,for64scans. The standard relative uncertainty for molecular mass calcu-lated via1H NMR arises from the choice of baseline and is estimated to be8%.The MALDI matrix,dihydrobenzoic acid(DHB),and the PEGDM and PEGUDM were dissolved in1mL of THF. Sodium was used as the cationizing reagent in a1:1by volume ratio of THF solution(0.5mg/mL solution in THF) and PEGDM or PEGUDM/DHB solution.All MALDI samples were deposited on the target by electrospray.The MALDI-TOF MS was performed on a Bruker(Billerica, MA)REFLEX II in reflectron mode using delayed extraction and low-mass(i.e.,matrix-ion)blanking as previously described.10Each spectrum shown is the sum of75discrete laser shots and is shown without smoothing or background subtraction.Estimated expanded uncertainty reported for MM moments arises from the choice of baseline and laser power (5%).The estimated standard uncertainty in overall signal intensity from repeatability studies is15%.Preparation of Hydrogels.Photopolymerized hydrogels were prepared according to a previously described proce-dure.9PEGDM or PEGUDM(10%or20%by mass fraction) and aqueous I2959solution(0.05%by mass fraction)were mixed in distilled deionized water or growth medium when chondrocyte is encapsulated in the hydrogel.Cylindrical samples of3mm in height and6mm in diameter were cured with a long wavelength UV source(365nm,300µW/cm2) for10min to obtain hydrogels.All hydrogels maintain their structural integrity for the entire time under static culture. Bovine chondrocytes were seeded into hydrogels at a cell density of17000cell/mL to100000cell/mL gel.Cell viability within the cell-hydrogel scaffolds under static cultures was measured at14d.Characterization of Hydrogels.FTIR was used to measure the bulk reaction kinetics.The methacrylic vinyl contents of PEGDM were analyzed by Fourier transform infrared spectroscopy.The infrared samples were films, approximately0.3mm thick,prepared by solvent casting a film from a solution of PEGDM and photoinitiator in dichloromethane.Spectra were recorded at2cm-1resolution on a Magna System550FTIR(Nicolet Instrument Tech-PEG Dimethacrylates and Their Hydrogels Biomacromolecules,Vol.5,No.4,20041281nologies,Madison,WI)equipped with a DTGS detector.The co-addition of 64scans gave adequate signal-to-noise.In situ rheology measurements were used for assessing the reaction kinetics and shear modulus.Rheological mea-surements were performed on a stress-controlled Rheometrics SR-5000rheometer in a parallel plate configuration (quartz plates,40mm diameter).The instrument was raised onto a platform,and a quartz Pen-Ray 5.5W mercury UV lamp was mounted under the bottom plate,allowing in-situ monitoring of the hydrogel formation.For these studies,a multi-wave UV lamp was used.Aqueous PEGDM or PEGUDM solutions containing 0.05%I2959photoinitiator by mass fraction were loaded into the rheometer.The sample was exposed to UV for a short time (1-2min)to allow the sample to cure without external perturbation.The late time cure was monitored by measuring the storage and loss modulus (G ′and G ′′,respectively)at 1rad/s and 1Pa as a function of reaction time.Duplicate experiments showed excellent reproducibity with relative standard uncertainty of 3%.The shear modulus was also determined using uniaxial compression measurements performed using a TA.XT2I HR Texture Analyzer (Stable Micro Systems,U.K.).This ap-paratus measures the deformation ((0.001mm)as a function of an applied force ((0.01N).Cylindrical hydrogels (height 3mm,diameter 6mm)were deformed (at constant volume)between two parallel glass plates.The shear modulus,G ,was calculated from the nominal stress,σ(force per unit undeformed cross-section),using the equation 11where Λis the macroscopic deformation ratio (Λ)L /L 0,L and L 0are the lengths of the deformed and undeformed specimen,respectively).Measurements were carried out in triplicate at deformation ratios 0.6<Λ<1.No volume change or barrel distortion was detected.Cell viability was determined as follows.The Calcein AM and Ethidium homodimer-1were added to chondrocyte media at a concentration of 2µM/mL.This live/dead assay was then added to the cell-seeded hydrogels and incubated at 37°C in 5%CO 2for 5min.Live and dead cells were imaged using an inverted microscope Eclipse TE 300with a TE-FM Epi-Fluorescence attachment (Nikon,Inc.).Digital pictures were taken using a Nikon Coolpix 990digital camera.Results and DiscussionsSynthesis and Characterization of PEGDM and PE-GUDM.PEGDMs and PEGUDMs of high purity and lowpolydispersity are prepared as model materials for the formation of photocrosslinkable hydrogels.The PEG hy-droxyl endgroups react with methacrylic anhydride to form PEGDM or with 2-isocyanatoethyl methacrylate to form PEGUDM (Figure 1).Urethane linkages in the PEGUDM are incorporated as an approach to enhance the hydrogen bonding in hydrogels,thus providing an additional adjustable parameter controlling the material properties.For the solution synthesis of PEGDM,we choose to use the less reactive methacrylic anhydride as opposed to the more commonly used methacryloyl chloride.The byproduct formed in the reaction of PEG with methacrylic anhydride is methacrylic acid,rather than the triethylamine/HCl salt formed in the reaction with methacrylic chloride.Since methacrylic acid can be removed more easily than the salt byproduct,methacrylic anhydride was used in these reactions.This allows for a straightforward oligomer purification process,which consists of one filtration through alumna followed by a single precipitation with diethyl ether.Given sufficient reaction time,only a slight excess of methacrylate anhydride relative to PEG hydroxyl is necessary to achieve quantitative conversion.Proton NMR and MALDI-TOF MS together provide comprehensive information regarding the degree of meth-acrylate conversion and product purity.Figure 2shows a typical 1H NMR spectrum of PEGDM.PEG has one main chemical shift at δ≈3.64.Under the current measurement conditions,the ethylene glycol penultimate endgroups cannot be differentiated from those of internal ethylene glycol segment.The chemical shift of methylene protons on MA are δ≈5.80and 6.21.Upon reaction of PEG,these protons shift to δ≈5.57and 6.13(peaks b and c),respectively.Moreover,the protons adjacent to the methacrylategroupsFigure 1.Synthesis of PEGDM andPEGUDM.Figure 2.1H NMR of 3k PEGDM.σ)G (Λ-Λ-2)1282Biomacromolecules,Vol.5,No.4,2004Lin-Gibson et al.shift to δ≈4.30.The 1H NMR spectra for PEGDM shows the expected peaks,but the lack of additional peaks suggests that unreacted methacrylic anhydride,methacrylic acid byproduct,and triethylamine all have been quantitatively removed.MALDI-TOF MS is a powerful technique from which the molecular mass,molecular mass distribution,and endgroup functionalities can be determined.Since MALDI detects all species within a discrete molecular mass range,it can be used to determine the amount of PEGDM versus the amount other impurities,such as PEGs with only one hydroxyl reacted (PEG mono-methacrylate)and unreacted PEG in a mixture.A MALDI-TOF MS spectrum of a typical 1k-PEGDM (Figure 3a)clearly illustrates both the high degree of methacrylate conversion and narrow polydispersity.Upon a closer examination (Figure 3b),three sets of peaks are observed.The main series corresponds to Na +cationized PEGDM.A minor second series of peaks corresponds to K +cationized PEGDM,and the third minor series may be attributed to H +cationized species.H +and K +contamination may occur during sample preparation and is common for the MALDI analysis of PEG and PEG derivatives.12H +is due to the matrix acid,and K +is in the matrix salt.Although the molecular mass calculation for the third series of peaks agrees with H +cationized PEGDM,it also agrees with thosecalculated for Na +cationized PEG mono-methacrylate.One approach to qualitatively differentiate the origin of these peaks is by comparing the M n of these different series.In the scenario that the peaks represent H +cationized PEGDM,the M n of the minor series should only differ from the main series by 22u (MM difference between Na +and H +),where as the M n difference should be higher (MM difference of ≈56u between PEGDM and PEGM)if the third series correspond Na +cationized PEG mono-methacrylate.The MALDI-TOF MS spectra of PEGDMs prepared from different molecular mass PEGs are shown in Figure 4.Intrinsic to MALDI analysis,the relative signal intensities decrease and the breadth of the peak appears to increase as the molecular mass increases.Each molecular mass can be clearly distinguished with all oligomers displaying the expected molecular mass distribution.The degree of conver-sion is quantitatively assessed for each product.As mentioned previously,the combination of 1H NMR and MALDI-TOF MS is necessary to gather the full picture of the product purity and degree of methacrylate conversion.From 1H NMR analyses,the molecular mass of PEGDMs can be calculated by comparing the peak intensities of ethylene glycol protons adjacent to the methacrylate (peak e)to internal ethylene glycol protons (peak d)or by comparing the peak integrations of a methacrylate proton (end group proton)to an ethylene glycol proton.However,since the unreacted PEG hydroxyl groups cannot be distin-guished by 1H NMR due to overlapping with PEG protons,the molecular mass calculation must assume stoichiometric conversion.This is not necessarily true depending on the reaction conditions employed in the synthesis.MALDI provides complementary information as to the amount of dimethacrylate species as well as those of PEG mono-methacrylate and unreacted PEG.On the other hand,PEG and methacrylated PEG derivatives are fragile in the MALDI analysis and could fragment during the laser desorption.The fragmentation may lead to biasing and,therefore,affect the MM calculations.Proton NMR provides confirmation to the MALDI calculations.It is only when the two techniques agree that we can conclude that high reaction conversions have been achieved.The molecular mass results of all PEGDMs are listed in Table 1.For all PEGDMs,the number average molecular masses (M n )obtained by 1H NMRmatchFigure 3.MALDI-TOF MS of 1k PEGDM,(a)full spectra and (b)expansion showing one main set of peaks 44u apart due to Na +cationized PEGDM and two minor sets of peaks of PEGDM cationized by K +and H +,respectively.Figure 4.MALDI-TOF MS of a series of PEGDMs.PEG Dimethacrylates and Their Hydrogels Biomacromolecules,Vol.5,No.4,20041283closely to those calculated by plementary techniques thus conclusively demonstrate the high reaction conversion and low impurity in these dimethacrylates. We have also explored the use of microwaves to prepare PEGDMs.Microwave reactions have gained significant interest recently due to their ability to achieve fast reaction rates often without the need for an organic solvent.13,14In the conventional thermal reaction,energy is transferred to the material through convection,conduction,and radiation. Energy transfers thus rely on diffusion of heat from the surfaces of the material,which leads to nonuniform heating and may cause excess heating at the surface leading to side reactions.Microwave energy can be delivered directly to material through molecular interaction with the electromag-netic field and can increase the local reaction kinetics,which leads to significantly reduced reaction time.Microwave reactions are becoming more widely used in combinatorial chemistry and green(solvent free)chemistry.The use of microwave reaction for the synthesis of PEGDM is particu-larly straightforward.The reaction requires5min to reach completion under microwave irradiation as opposed to4d for solution reactions.In addition,microwave-assisted reac-tions do not require a solvent or catalyst,and the product can be precipitated simply by adding diethyl ether.For the microwave preparation of PEGDMs,the ratio of PEG to MA and optimized reaction times are important in achieving high reaction conversions.Whereas the solution reaction requires only a slight excess of MA relative to PEG, a near stoichiometric conversion by the microwave reaction is facilitated by a larger amount of MA relative to PEG.Table 2shows the effect of reaction time and reagent ratio on the reaction conversion.The effect of reaction time can be compared for the microwave reactions of1k PEGDM with the same reagent stoichiometric ratio of MA to PEG as the solution reaction,i.e.,2.2.The conversion increases with increased reaction time,but does not reach high conversion even after10min reaction time.Clearly the dominating effect in achieving high conversion is the MA to PEG ratio where a monotonic increase in reaction conversion is observed with an increased MA to PEG ratio.At a MA to PEG ratio of10, a near stoichiometric conversion can be achieved after5min. Since the microwave reaction is carried out neat,the lack of molecular mobility may require an excess of MA to be present locally.It is interesting to note that,although the reaction temperature becomes elevated during the microwave reaction,we do not detect cross-linking or any other side reaction in the product.Both the1H NMR and MALDI are nearly identical for PEGDMs prepared by the solvent approach or the microwave-assisted route.The effect of PEG molecular mass on conversion is also evaluated for the microwave-assisted reactions.Table2 shows the percent conversion calculated from the1H NMR results for1k and4k PEGDM reacted using various MA to PEG ratios for the same length of reaction time.Although PEGs are crystalline at room temperature,reaction mixtures are heated above the melting temperatures during microwave irradiation;thus,no significant differences between the reaction conversion for1k and4k PEG are observed. Solution preparation of PEGUDMs is done in a similar manner as the PEGDMs.The isocyanate group on IEM is reacted with PEG hydroxyl groups.Polyurethane and related polyurethane copolymers have been used in various biologi-cal applications,such as heart valve implants;therefore,the urethane linkages used in the current study are expected to have relatively low cytotoxicity.The urethane spacer pro-vides additional hydrogen bonding sites that may enhance the mechanical properties.Moreover,urethane linkages may be degradable under certain conditions.The PEGUDMs prepared from various PEG precursors are also characterized using a combination of1H NMR and MALDI-TOF MS. Figure5shows a typical1H NMR of3k PEGUDM.The expected peaks are observed for the PEGUDM products. The MALDI-TOF MS of PEGUDMs synthesized from various molecular mass PEGs are shown in Figure6.Similar to the PEGDM spectra,the intensities generally decrease and breadth of distribution increases with increased molecular mass.The intensity is slightly higher for the3k PEGUDM than for the2k PEGUDM since a higher reaction conversion is obtained for the3k polymer.The insert of Figure6shows the expanded spectra of the3k PEGUDM.Two series ofTable1.Molecular Mass Results(g/mol)of PEGDM Obtained Using1H NMR and MALDI-TOF MSPEG M n(NMR)M n(MALDI)M w(MALDI)PDI 1k104710641085 1.02 2k222221502178 1.01 3k342432363283 1.01 5k505746304681 1.01 8k833386808776 1.01Table2.Reaction Conversion of PEGDMs Synthesized by the Microwave Process Calculated by1H NMRPEG M n MA/PEG(mol:mol)reaction time(min)%conversion1k 2.22292.25402.21068458410596 4k 2.2537457910599Figure5.1H NMR of a3k PEGUDM.1284Biomacromolecules,Vol.5,No.4,2004Lin-Gibson et al.peaks are clearly distinguishable.The main series with higher peak intensities (S1)corresponds to Na +cationized PEGUDM.Endgroup analysis using the Polymerics software suggests that the minor series (S2)corresponds to Na +cationized PEG mono-urethane methacrylate.This is in agreement with the difference in M n calculated for the two series,which correlates well with the molecular mass difference of an endgroup.1H NMR confirms this peak assignment,and this is described in detail in the following paragraph.Table 3lists the reaction conversions for PEGUDM calculated by 1H NMR and MALDI-TOF MS.From 1H NMR,we can calculate an apparent molecular mass by comparing the methylene protons adjacent to the urethane (peak d)vs internal PEG protons (peak g).Since the molecular mass of PEG is known,we can calculate a theoretical M n of PEGUDM at 100%reaction conversion.It is thus possible to back calculate the reaction conversion by comparing the apparent M n to the theoretical M n .To calculate the reaction conversion from MALDI,the peak integrations of the two series (S1and S2)are first calculated.The total reaction conversion is then the sum of S1and half of S2.As shown in Table 3,the reaction conversions obtained from the very different techniques are statistically identical.It is noted that although the reaction conversions are relative high,the synthesis of PEGUDM does not reach a near stoichio-metric conversion as is the case for the PEGDM reactions.Preparation and Characterization of Hydrogels.The reaction kinetics of the cross-linking of bulk PEGDM and PEGUDM are monitored by FTIR.From the FTIR spectrum,a decrease in the C d C stretch and a shift in the C d O stretch are observed as the methacrylate groups react.As shown inFigure 7a,high vinyl group conversions can be achieved after 15min irradiation for the bulk reactions of PEGDM.Similar studies are carried out for PEGUDMs (Figure 7b).The bulk reaction kinetics appear to be similar for PEGDM andPEGUDM.Figure 6.MALDI-TOF MS of PEGUDMs prepared from different molecular mass PEGs.The insert shows an expanded spectrum of 3k PEGUDM.Table 3.Percent Reaction Conversion of PEGUDM Synthesis Calculated by 1H NMR and MALDI-TOF MSMALDI %conversion PEG NMR %conversionS1S2total 1k 958714932k 806436823k 898317925k 938713948k85663483Figure 7.FTIR of bulk photocure of (a)4k PEGDM and (b)5k PEGUDM monitored as a function of UV exposuretime.Figure 8.Storage modulus measured as a function of UV irradiation time for aqueous PEGDM (10%by mass fraction).PEG Dimethacrylates and Their Hydrogels Biomacromolecules,Vol.5,No.4,20041285Reaction kinetics and gel mechanical properties of hy-drogels are studied by in situ rheological studies.Hydrogels are prepared by loading low viscosity,photoinitiatior-containing,aqueous PEGDM or PEGUDM solutions between two parallel plates followed by irradiation to cross-link the dimethacrylates.Since the solutions are confined between parallel plates,a certain amount of stress is always built into the as-prepared hydrogels.When submersed in water or growth medium,these hydrogels can swell or contract depending on their thermodynamic state.In addition,PEG hydrogels produced by the free radical polymerization have high spatial inhomogeneity.Relationships between gel structures and properties will be the subject of a future paper.In the present study,only preliminary data determined by rheology on the gel modulus as-prepared in the confined stateis discussed.Two measurements are examined for each sample:a time-sweep measurement in which the storage modulus (G ′)and loss modulus (G ′′)are monitored as a function of irradiation time and a subsequent frequency sweep measurement at low strain amplitude.From the time sweep (Figure 8,only G ′is shown for clarity),the reaction kinetics can be qualitatively evaluated.During the course of the reaction,both G ′and G ′′increase,and G ′becomes greater than G ′′once gelation occurs.The storage modulus G ′increases as the reaction progresses for several orders of magnitude and eventually plateaus.The time at which the G ′reaches a plateau provides a rough estimate of the time it takes to complete the photocrosslinking reaction.It should be noted that the light source used in the rheological measurements was of a different intensity and wavelength;therefore,although the trends in the curing rate are correct,the kinetics determined here cannot be used directly to predict the rate of curing under long UV wavelength.The subsequent frequency sweep verifies the formation of a chemically cross-linked gel.It is also of interest to examine the slope of G ′as a function of frequency which provides qualitative information regarding the strength of the gel.All PEGDM and PEGUDM gels show relatively weak frequency depen-dence in the frequency range examined,confirming that the gels are in fact cross-linked and that gels as prepared are mechanically robust.The shear moduli of hydrogels were also measured using a uniaxial compression test and calculated using equations derived from the strain-energy function.Figure 9shows the shear modulus of PEGDM hydrogels prepared from different molecular mass oligomers (2k,4k,and 8k)and as a function of PEGDM mass fraction (varying from 10%to 30%).AsFigure 9.Shear modulus of hydrogels prepared using various PEGDM molecular masses and at various massfractions.Figure 10.Live stain (top)and dead stain (bottom)of PEGDM (left column)and PEGUDM (right column)hydrogels containing bovine chondrocytes.The cell density is 100000cell/mL.1286Biomacromolecules,Vol.5,No.4,2004Lin-Gibson et al.。