PEO-PPO-PEO嵌段共聚物温敏特性及其影响机制的分子模拟

以Pluronic P85为例,采用全原子分子动力学模拟方法研究了单链嵌段类共聚物PEO-PPO-PEO在不同溶剂中的温敏性相转变行为及其影响机制。分子模拟结果显示当Pluronic P85溶解在水溶液和极性有机溶剂（甲醇）中时,升温导致PPO和PEO与水或甲醇分子间氢键断裂、使得溶剂化壳层被破坏而释放出水或甲醇分子,Pluronic P85发生构象塌缩,呈现反向温度响应特性。当Pluronic P85溶解在非极性有机溶剂（甲苯）中时,升温导致分子热运动加剧而削弱Pluronic P85链分子内相互作用,使其在甲苯中的构象更加舒展,呈现正向温敏特性。分子模拟结果还展现了PEO和PPO链段的溶剂化效应随温度的变化及其对于聚合物构象的影响,对于此类聚合物的分子设计和应用提供了理论依据。     

固定化酶催化制备乙酸正丁酯及动力学

酯交换反应可用南极假丝酵母脂肪酶B（CALB）作催化剂,采用溶胶-凝胶法固定脂肪酶CALB得到的催化剂颗粒可用于乙酸乙酯和正丁醇的酯交换反应。首先探究了固定化酶的稳定性和重复使用性,然后在间歇反应釜内进行反应动力学实验,考察了转速、催化剂用量、酯醇比、温度等因素对反应的影响,确定了适宜的操作条件。在328.15～343.15 K下,将实验数据拟合得到反应的动力学方程,通过实验值与计算值的比较,验证此宏观动力学方程合理,可用于模拟计算。     

酶催化一步法制备高分子质量PBSA共聚酯及其性能

聚丁二酸丁二醇酯(PBS)是一种具有广阔发展前景的生物基聚酯品种,但由于其分子链段柔性较高并且结晶度高,在实际应用过程中仍然面临热性能、力学性能、降解性能不足的弊端。选用条件更为温和的酶催化体系,以丁二酸二乙酯、己二酸二乙酯、丁二醇为原料,Novozym-435(固定化CALB酶)为催化剂,甲苯为溶剂,合成制备了一系列高分子质量的聚(丁二酸丁二醇-co-己二酸丁二醇)(PBSA)三元共聚酯。在反应温度80℃、酶的质量分数为10%的条件下,所制备的PBS与PBSA共聚酯的数均分子质量在18 400～21 200 g/mol,多分散性指数在1.7～2.0之间。采用核磁共振谱仪对制备的共聚酯产物的化学结构进行了表征。TGA结果表明,酶催化体系下的PBSA共聚酯的热稳定性要高于熔融体系下的产物。DSC与WAXD的结果表明,引入己二酸链段后,PBS的结晶能力下降。酶催化反应避免了重金属催化剂的使用,进一步拓宽了PBS在生物医药领域范围的潜在应用。     

纳米酶催化剂制备方法研究进展

酶催化具有化学、区位和立体选择性,这使得其成为绿色合成化学品的理想催化剂。然而,天然酶常因其在工业催化条件下的活性和稳定性较低而难以使用。纳米技术为构建高效酶催化剂提供了新的可能性。通过简便、高效、低成本的方法制备出具有高催化活性和高稳定性的纳米酶催化剂,同时提高纳米酶催化剂的可操作性和可回收重复使用特性是其中的关键问题。介绍了纳米酶催化剂的研究现状和制备方法,重点介绍了采用共沉淀方法制备酶-无机晶体杂化纳米催化剂、酶-金属有机骨架材料杂化纳米催化剂,以及制备具有温度和磁响应特性的纳米酶催化剂,并对纳米酶催化剂在酶催化合成医药化学品方面的应用前景进行了探讨。     

纳米酶催化剂制备方法研究进展

酶催化具有化学、区位和立体选择性,这使得其成为绿色合成化学品的理想催化剂。然而,天然酶常因其在工业催化条件下的活性和稳定性较低而难以使用。纳米技术为构建高效酶催化剂提供了新的可能性。通过简便、高效、低成本的方法制备出具有高催化活性和高稳定性的纳米酶催化剂,同时提高纳米酶催化剂的可操作性和可回收重复使用特性是其中的关键问题。介绍了纳米酶催化剂的研究现状和制备方法,重点介绍了采用共沉淀方法制备酶-无机晶体杂化纳米催化剂、酶-金属有机骨架材料杂化纳米催化剂,以及制备具有温度和磁响应特性的纳米酶催化剂,并对纳米酶催化剂在酶催化合成医药化学品方面的应用前景进行了探讨。     

毕赤酵母表面展示脂肪酶催化合成肉豆蔻酸糖酯

研究了毕赤酵母表面展示脂肪酶(CALB)全细胞催化剂的较佳活性条件,结果显示,适宜的反应温度为50~60℃。以CALB为催化剂,比较了不同底物对糖酯合成的影响。以1,2-O-异亚丙基-D-呋喃葡萄糖(Ip Glc)为酰基受体,肉豆蔻酸为酰基供体,考察了有机溶剂种类、CALB的添加量、底物摩尔比、分子筛的添加量、初始水活度对合成6-O-肉豆蔻基-1,2-O-异亚丙基-α-D-呋喃型葡萄糖酯(Ip Glc-C14)的影响,得到较佳的合成条件为:丙酮5 m L、CALB(干粉)0.3 g、n(Ip Glc)∶n(肉豆蔻酸)=1∶3(其中Ip Glc 0.5 mmol)、4A分子筛0 g、初始水活度a_w=0.11、反应温度50℃、200 r/min反应72 h。在此条件下,Ip Glc-C14的收率为91.25%。比较了CALB和固定化脂肪酶Novozym 435对Ip Glc-C14合成的反应进程的影响,结果显示使用Novozym 435的反应速率快,而CALB的最终收率较高。     

固定化酶催化制备乙酸正丁酯及动力学

酯交换反应可用南极假丝酵母脂肪酶B(CALB)作催化剂,采用溶胶-凝胶法固定脂肪酶CALB得到的催化剂颗粒可用于乙酸乙酯和正丁醇的酯交换反应。首先探究了固定化酶的稳定性和重复使用性,然后在间歇反应釜内进行反应动力学实验,考察了转速、催化剂用量、酯醇比、温度等因素对反应的影响,确定了适宜的操作条件。在328.15~343.15 K下,将实验数据拟合得到反应的动力学方程,通过实验值与计算值的比较,验证此宏观动力学方程合理,可用于模拟计算。     

Pluronic嵌段共聚物胶束作为靶向药物载体

聚氧乙烯 聚氧丙烯 聚氧乙烯 (PEO PPO PEO)三嵌段共聚物 (商品名为Pluronics)在水溶液中能自发生成多分子聚集的胶束 ,这些胶束主要以疏水的PPO嵌段为内核 ,PEO嵌段环绕在外构成外壳 ,这种胶束可以有效地增溶油溶性药物。Pluronic嵌段共聚物无毒、无刺激、无免疫原性 ,胶束外壳的PEO嵌段能阻止血小板的聚集。胶束尺寸和病毒相仿 ,其大小适合在体内传输。初步尝试表明 ,胶束表面嵌上合适的抗体可以将增溶了模型药物的Pluronic胶束定向输送到动物脑部 ,从而提高了药效 ,降低了副作用。实验表明 ,Pluronic嵌段共聚物胶束可能成为将多种药物导向特定部位的有效载体。     

二元Pluronic嵌段共聚物相互作用 I.PPO嵌段长度相近的P94/L92和F108/L92二元混合水溶液

以I2 作为探针 ,用可见光度方法测定不同浓度比例的P94/L92和F10 8/L92二元Pluronic嵌段共聚物水溶液的临界胶束浓度。实验结果表明 ,这些PPO嵌段长度相近的分子在全部浓度比例范围内都发生相互作用 ,生成了混合胶束。由于这些分子的PEO嵌段长度不等 ,随着具有较短PEO嵌段的L92分子加入 ,P94/L92和F10 8/L92混合胶束外壳的EO基团数减少 ,从而使混合胶束水化度降低     

具协同催化效应的毕赤酵母全细胞催化生物柴油制备

以表面共展示具协同催化效应的南极假丝酵母脂肪酶B(Candida antarctica lipase B,CALB)与嗜热丝孢菌脂肪酶(Thermomyces lanuginosus lipase,TLL)重组毕赤酵母全细胞作为催化剂催化生物柴油制备,考察了生物柴油制备条件,并进行了初步优化。结果表明,共展示CALB与TLL脂肪酶毕赤酵母全细胞在叔丁醇介质体系中可有效催化生物柴油制备。冻干酵母细胞量0.31 g/g油,醇油摩尔比4∶1,温度35℃,反应36 h,生物柴油得率达86.25%。     

Emulsifying properties,of block copolymers. Oil-water emulsions and microemulsions

The emulsifying effect of poly(styrene-b-ethylene oxide) block copolymers (Cop PS-PEO) has been studied for the toluene-water system as a function of the molecular characteristics of the copolymer (composition, molecular weight, and structure). To demonstrate the surfactive properties of Cop PS-PEO, we determined the interfacial tension γ_i for the toluene-water system in the presence of these block copolymers. For oil/water (O/W) and water/oil (W/O) emulsions, prepared in the presence of Cop PS-PEO, we determined the phase inversion point, the particle size of the dispersed phase, the stability and the viscosity as a function of the PEO content, the molecular weight, and the structure of the block copolymers. It appeared that the best results for the emulsification are obtained with Cop PS-PEO having molecular weights less than 100, 000. Stable O/W emulsions of small particle size are preferentially prepared with di- or triblock copolymers having a PEO content of 60-80 percent. In contrast, stable W/O emulsions are obtained with diblock copolymers having a PS content of 60-80 percent. The difference in behavior between diand triblock copolymers also showed the importance of the chain conformation at the toluene-water interface. As an extension, we have shown that microemulsions can be obtained with such polymeric surfactants. Isopropanol and butylamine appeared to be efficient cosurfactants for the system water/toluene/Cop PS-PEO.     

Controlling the morphology of polybutadiene-poly(ethylene oxide) diblock copolymers in bulk and the orientation in thin films by attachment of alkyl side chains

A polybutadiene₁₉-block-poly(ethylene oxide)₉₄ (PB-PEO) has been modified by free-radical additions of 2-ethylhexanethiol, 1-decanethiol, and 1-dodecanethiol separately to the PB block. The block copolymers were characterized by DSC, SAXS, XRD and AFM measurements. Above the melting temperature of PEO, PB-PEO showed hexagonal morphology having PB cylinders in the PEO matrix. The addition of alkyl side chains decreased the volume fraction of PEO and the morphology changed to lamellar for ethylhexyl side chains and to reversed hexagonal morphology with PEO cylinders in the PB/alkyl chain matrix for decyl and dodecyl side chains. Below the melting temperature of PEO, all polymers showed lamellar morphology. In the case of dodecyl side chains, the lamellar morphology oriented perpendicular to the air/film interface and was stable against high temperature annealing.     

Use of poly(styrene)-block-poly(ethyleneoxide) as emulsifier in emulsion polymerization

Summary Poly(styrene)-block-poly(ethyleneoxide), abbreviated as (PS-b-PEO) were used as emulsifiers in emulsion polymerization of styrene and methyl methacrylate. The block copolymers had a poly(styrene) block with M_n=1000 g/mol and a poly(ethyleneoxide) block with M_n=1000, 3000 or 5000 g/mol, respectively. Stable dispersions were obtained when the PEO block molecular weight was higher than 1000 g/mol. Also the amphiphilic properties of the copolymers depended on the PEO chain length. Block copolymer micelles with hydrodynamic radii between 11 and 17nm were observed. Emulsion polymerization was performed at different block copolymer concentration at 60 and 80°C. Particle size varied between 50 and 300nm and decreased with increasing copolymer concentration. The particle size was larger at higher temperature, but the size distribution was narrower. Polymerization of methyl methacrylate gave smaller particles when compared to styrene. The dispersions were very stable towards high electrolyte concentration, but flocculation occurred at elevated temperatures. Both observations indicate that the dispersions are sterically stabilized.     

PS—b—PEO—b—PS三嵌段共聚物的结晶形态和微相分离——（Ⅰ）PEO含量及分子量的影响

采用偏光显微镜和透射电镜研究了PS-b-PEO-b-PS三嵌段共聚和折结晶形态和微相分离,重点讨论了PEO含量和分子量的影响,实验发现,当共聚物中的PEO分子量低至6000、含量低于42%时,均有球晶生成,且随着PEO含量的升高,球晶形态变得更加完善,TEM结晶显示,当PEO分子量为1000含量分别为93%和91%时,形成以PEO为连续相,PS为分散相的微相分离结构,但当PEO含理降低到77%时,发生了相反转,PEO变为分散相,PS变为连续相,当PEO分子量为6000,含量为42%时,形成了以PS为连续相,PEO为分散相的微相分离结构,所有的分散相都有球形或近似球形的形貌,在PEO的分子量为2000,含理为18%,34%时,发现了层状微相分离结构,同时我们还发现,pH=6.0的磷钨酸水溶液是该类嵌段共聚物的有效染色体系。     

Preparation of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) particles in O/W emulsion

In the present paper, we investigate the preparation of polymeric particles based on the biodegradable polyester poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). A new technique for PHBV particle preparation has been developed. This method utilizes the thermoreversible gelation of PHBV in toluene. Particles have been obtained by the secondary dispersion technique in a three-step procedure: (a) preparation of PHBV solution in toluene; (b) preparation of O/W emulsion by ultrasound followed by the gel formation in toluene/PHBV droplets; and (c) toluene extraction. In the present study we investigated the influence of the stabilizer type and its concentration in the aqueous phase, ultrasound power, and PHBV concentration in toluene on the size and stability of the formed droplets as well as the final PHBV particles. It has been found that PEO/PS block copolymers are the best stabilizers for the present system as compared to conventional tensides such as SDS or CTAB. It has been found that PEO/PS block copolymers allow obtaining PHBV particles with a regular shape and controlled dimensions after toluene extraction. The minimal size of the PHBV particles obtained by this technique was ca. 100 nm. The obtained particles exhibit a relatively broad particle size distribution and the particle shape is strongly affected by the block copolymer composition, ultrasound power and the way of toluene extraction.     

PS-b-PEO-b-PS三嵌段共聚物的结晶形态和微相分离(I)PEO含量及分子量的影响

采用偏光显微镜和透射电镜研究了 PS-b-PEO-b-PS三嵌段共聚物的结晶形态和微相分离 ,重点讨论了 PEO含量和分子量的影响。实验发现 ,当共聚物中的 PEO分子量低至 60 0 0、含量低至 4 2 %时 ,均有球晶生成 ,且随着 PEO含量的升高 ,球晶形态变得更加完善。 TEM结果显示 ,当 PEO分子量为1 0 0 0 0、含量分别为 93%和 91 %时 ,形成以 PEO为连续相、PS为分散相的微相分离结构 ;但当 PEO含量降低到 77%时 ,发生了相反转 ,PEO变为分散相 ,PS变为连续相。当 PEO分子量为 60 0 0 ,含量为 4 2 %时 ,形成了以 PS为连续相、PEO为分散相的微相分离结构。所有的分散相都有球形或近似球形的形貌。在 PEO的分子量为 2 0 0 0、含量为 1 8%、34 %时 ,发现了层状微相分离结构。同时我们还发现 ,p H=6.0的磷钨酸水溶液是该类嵌段共聚物的有效染色体系     

Synthesis of Red-Light-Responsive Pheophorbide-a Tryptamine Conjugated Photosensitizers for Photodynamic Therapy

Six methyl pheophorbide-a derivatives were prepared by linking a tryptamine side chain at the C-13 ¹ , C-15 ² and C-17 ³ positions of pheophorbide-a. P repared conjugates were characterized and evaluated for their photocytotoxicity against A549 cells. The conjugate 6 a with strong absorption at 413 nm (Soret band), 663–671 nm (Q bands) and comparable fluorescence quantum yield (0.26) was found to exhibit significant cytotoxicity (659 nM). Molecular integration of pheophorbide-a and tryptamines showed synergistic effects as the most potent conjugate 6 a was identified with enhanced photocytotoxicity when compared to methyl pheophorbide-a. T he conjugate 6 a was smoothly taken up by A549 cells and exhibited intracellular localization predominantly to lysosome in the cytoplasm. Upon photoirradiation 6 a generated singlet oxygen to show potent cytotoxicity toward A549 cells.     

Novel polyrotaxanes comprising γ-cyclodextrins and Pluronic F127 end-capped with poly(N-isopropylacrylamide) showing solvent-responsive crystal structures

Herein novel polyrotaxanes (PRs) comprising γ-CDs and Pluronic F127 end-capped using poly(N-isopropylacrylamide) blocks were prepared via the atom transfer radical polymerization in aqueous medium at room temperature. The structure was characterized in detail by ¹H NMR, 2D NOESY NMR, FTIR, GPC, WXRD and DSC analyses. Solvent treatments were conducted on the resulting PRs via incubation in water and DMF, respectively. Interestingly the treatments resulted in two crystal structures: the DMF-incubated PRs appeared to give a novel crystal structure, while the water treated samples yielded a typical channel-type crystal structure. The entrapped γ-CDs were found to be aggregated mainly around the central PPO segment in the DMF-incubated PRs while some of γ-CDs were randomly dispersed on the PEO segments in the water treated samples. The two crystal structures exhibited a strong solvent dependence and were convertible through solvent incubation. The solubility and flexibility were greatly changed with the crystal structure conversion. Hence this provides an opportunity to alter the physical properties of PRs without any chemical modification of entrapped CDs. The aggregated/dispersed state of γ-CDs along the Pluronic F127 chain as a result of response to solvent treatment renders the PRs great potential to be used as smart materials.     

PE-b-PEO嵌段共聚物的合成及其芳烃/烷烃渗透汽化分离性能

采用阴离子聚合方法合成了具有不同环氧乙烷聚合度的聚丁二烯-b-聚环氧乙烷嵌段共聚物(PB-b-PEO嵌段共聚物),然后催化加氢得到聚乙烯-b-聚环氧乙烷嵌段共聚物(PE-b-PEO嵌段共聚物),使用凝胶渗透色谱仪(GPC)、核磁共振氢谱(1H-NMR)对共聚物进行了分析,结果表明所得聚合物具有预定的结构。通过熔融压片的方法制备PE-b-PEO嵌段共聚物均质膜,考察了PE-b-PEO嵌段共聚物分子链中聚环氧乙烷的聚合度对渗透汽化分离性能的影响。