基于高分子侧链主客体识别构筑光响应超分子水凝胶

制备了侧链含α-环糊精(α-CD)的聚丙烯酸(PAA-α-CD)作为主体聚合物,侧链含偶氮基团(Azo)的聚丙烯酰胺(PAM-Azo)作为客体聚合物.利用1H NMR、2D NOESY NMR方法测定了PAA-α-CD与PAM-Azo间的主客体作用.结果表明,PAM-Azo侧链的trans-Azo基团能够被PAA-α-CD侧链的α-CD包结,而cis-Azo基团不能被α-CD包结.在一定浓度下,PAA-α-CD与PAM-Azo通过主客体间的识别能够形成超分子水凝胶,并且该凝胶具有光响应性.在365nm紫外光光照下,PAM-Azo侧链的trans-Azo转变为cis-Azo,不能被PAA-α-CD侧链的α-CD包结,超分子水凝胶转变为溶胶.而在430nm的可见光光照下,PAM-Azo侧链的cis-Azo转变为trans-Azo,重新被PAA-α-CD侧链的α-CD包结,又可得到超分子水凝胶.     

聚乙二醇相对分子质量及用量对温敏型PCL-PEG-PCL水凝胶的制备及释药性研究

采用开环聚合法制备PCL-PEG-PCL共聚物,并将其制成温敏性水凝胶,探究了PEG(聚乙二醇)相对分子质量及质量浓度对水凝胶温敏性的影响.水凝胶的相变温度由翻转小瓶法测定.通过FTIR、热分析仪和SEM等技术对其组成及结构进行表征.以疏水性姜黄素(Cur)为模型药物,制备出载Cur PCL-PEG-PCL水凝胶,并研究其体外释药行为.FTIR结果表明:实验制备的共聚物中含有PCL和PEG的链段.热分析结果表明:在25℃~65℃内水凝胶存在相变过程.SEM结果表明:水凝胶剖面具有疏松多孔.体外释药结果表明:PCL-PEG-PCL水凝胶对Cur具有缓释作用,释药机理符合Higuchi骨架溶蚀模型.     

基于功能化聚磷酸酯嵌段共聚物的微凝胶和水凝胶的制备与表征

首先利用聚乙二醇单甲醚(MePEG)作为引发剂前体,对含有炔基的环状磷酸酯单体2-炔丁基-2-氧代-1,3,2-二氧磷杂环戊烷(BYP)进行开环聚合,制备两嵌段共聚物MePEG-b-PBYP.随后,采用巯基-炔(Thiol-yne)点击化学反应对PBYP的炔基进行修饰,分别获得侧链含氨基(—NH2)、羧基(—COOH)和磺酸钠(—SO3Na)的聚磷酸酯嵌段共聚物,在水相中形成聚电解质.通过NMR和GPC对产物的结构和组成进行表征.MTT测试表明,两嵌段共聚物具有较好的生物相容性.进一步将带有不同电荷的聚电解质溶液混合,利用静电作用制备微凝胶.通过DLS、TEM及SEM等测试对聚合物的溶液行为及微凝胶的形貌进行表征.为增强凝胶体系的物理交联作用,将α-环糊精(α-CD)引入体系,诱导形成水凝胶.利用SEM对水凝胶的形貌进行表征,XRD分析水凝胶的包结络合作用,并利用流变仪测试水凝胶的凝胶化时间.该水凝胶以其良好的生物相容性、生物可降解性和一定的机械强度等性能,有望作为可注射型凝胶材料,在药物控释和组织工程等领域具有潜在的应用.     

温敏性PCL-PEG-PCL水凝胶的合成、表征及蛋白药物释放

考察了温敏性PCL-PEG-PCL水凝胶中聚乙二醇(PEG)及聚己内酯(PCL)不同嵌段组成对其溶胶-凝胶相转变温度以及亲水性药物(牛血清白蛋白, BSA)释放速率的影响. 采用开环聚合法, 以辛酸亚锡为催化剂、PEG1500/PEG1000为引发剂, 与己内酯单体发生开环共聚, 合成了一系列具有不同PEG和PCL嵌段长度的PCL-PEG-PCL型三嵌段共聚物. 通过核磁共振氢谱及凝胶渗透色谱对其组成、结构及分子量进行了表征. 共聚物的溶胶-凝胶相变温度由翻转试管法测定. 利用透射电镜、核磁共振氢谱及荧光探针技术证实了该材料在水溶液中胶束的形成. 以BSA为模型蛋白药物, 制备载药水凝胶, 利用microBCA法测定药物在释放介质中的浓度, 研究其体外释放行为. 实验结果表明, 共聚物的溶胶-凝胶相变温度与PCL及PEG嵌段长度紧密相关, 即在给定共聚物浓度情况下, 固定PEG嵌段长度而增加PCL嵌段长度, 会导致相变温度降低; 而固定PCL嵌段长度而增加PEG嵌段长度, 其相变温度相应升高. 水凝胶中蛋白药物的释放速率与疏水的PCL嵌段长度无关, 而与亲水的PEG嵌段长度密切相关, 即PEG嵌段越长, 蛋白药物释放越快.     

化学交联葡萄糖基取代聚膦腈水凝胶制备和胰岛素释放研究

在合成了葡萄糖基和甲氧乙氧基共取代聚膦腈的基础上,进一步通过向聚膦腈主链引入一定量带自由氨基的取代基,与戊二醛反应交联后,获得了具有化学交联点的聚膦腈水凝胶.该水凝胶与伴刀豆球蛋白(Con A)结合后,水凝胶的溶涨平衡性能表现出对葡萄糖浓度的依赖性.将负载有胰岛素的聚膦腈水凝胶交替置于含不同葡萄糖浓度(4 mg/mL和1 mg/mL)的介质中,可检测到在高浓度葡萄糖环境下,胰岛素的释放明显加快,而当葡萄糖的浓度降低后,在一段时间内几乎检测不到胰岛素的释放,但随着浸泡时间的延长,仍会逐渐出现胰岛素从凝胶缓慢扩散释放的现象.以上研究表明,化学交联的葡萄糖基取代聚膦腈水凝胶可用于对胰岛素的葡萄糖响应释放.     

光聚合α-CD组装超分子结构水凝胶的合成与表征

1990年, Harada等[1,2]首先观察到α-环糊精(α-CD)与PEG形成的结晶包结物(ICs). 进一步的研究发现, n=400～10 000的PEG均能与α-CD形成结晶ICs, 其形成速率与n有关, n=1 000的PEG形成ICs的速率最快. 由于α-CD是通过与相邻α-CD的氢键作用、空间立体配位及其疏水空腔与聚合物链形成包结物, 这种包结物也称为多聚准轮烷.     

基于硼酸邻苯二酚酯键的硼替佐米pH敏感型可控释放模型的研究

通过硼酸邻苯二酚酯键将抗癌药物硼替佐米(bortezomib,BTZ)连接到两亲型梳状聚衣康酸接枝共聚物(PIA-PEG-DDA-DPA)上,制备pH敏感型载药聚合物PIA-PEG-DDA-DPA-BTZ.通过核磁共振(NMR)表征了该聚合物的结构.DLS和AFM测试结果表明,该聚合物流体力学直径较小约为25~38 nm;芘荧光法测定表明,其临界胶束浓度(CMC)为2.54×10-3mg/mL.利用硼替佐米位于310 nm处的紫外特征吸收峰,分别在模拟生理pH值(7.4)及溶酶体和内涵体pH值(5.0)的条件下,研究聚合物的释药行为,结果表明,该体系在生理pH环境下基本无释药行为,在溶酶体和内涵体pH环境下,BTZ的累计释放率随时间变化曲线符合一级动力学方程Q=61.65866-62.13481e-0.32544t.相关的细胞实验表明,该种载药聚合物体系对癌细胞的抑制作用明显,接近硼替佐米纯品的效果.     

聚(L-谷氨酸)水凝胶的Diels-Alder制备及其生物分子响应性研究

报道了一种含有二硫键的聚L-氨基酸共价交联网络,制备了能对含巯基生物分子与蛋白酶产生响应的新型聚L-氨基酸水凝胶.通过二硫键将降冰片烯基团键合在聚(L-谷氨酸)侧链,所得到的聚合物与末端修饰四嗪基团的四臂聚乙二醇在水溶液中混合,通过降冰片烯与四嗪基团之间发生Diels-Alder反应形成分子间共价交联,获得了聚(L-谷氨酸)/聚乙二醇水凝胶.研究了水凝胶在含巯基生物活性分子谷胱甘肽(GSH)作用下的性质变化.结果表明,2种官能化聚合物混合后可快速形成稳定的水凝胶,其力学性质随聚合物浓度、2种聚合物比例和降冰片烯基团的取代度的改变而变化.体外降解实验结果表明,在GSH或弹性蛋白酶存在的条件下,水凝胶的降解速率显著增加.同时,经GSH处理的水凝胶机械强度也显著降低.大鼠体内实验表明,在交联点引入GSH响应性的二硫键会明显加速聚氨基酸水凝胶的体内降解.进一步体外细胞实验与组织学分析结果表明,所获得聚氨基酸/聚乙二醇水凝胶具有良好的体外细胞相容性和动物体内组织相容性.     

海藻酸钠水凝胶的制备及其在药物释放中的应用

近年来,由于智能水凝胶在药物的控制释放、基因传送、组织工程等领域的应用前景诱人,研究者对智能水凝胶的研究十分活跃。合成类水凝胶常用的单体有丙烯酸及其衍生物、丙烯酰胺及其衍生物等,合成水凝胶具有较好的稳定性,但其生物降解性和生物相容性较差。天然类水凝胶的原料主要有壳聚糖、海藻酸钠、纤维素、淀粉等。由于这些天然多糖具有较好的生物相容性和生物降解性,同时价廉易得,因此,天然类水凝胶在药物控制释放领域更具有优势。海藻酸钠是β-D-甘露糖醛酸(β-D-mannuronic,M)和α-L-古洛糖醛酸(α-L-guluronic,G)按照(1→4)糖苷键连接而成的线型聚合物,每个糖醛酸单元上含有一个羧基,因此,海藻酸钠在中性或碱性条件下呈现聚阴离子电解质的性质。本文综述了海藻酸钠水凝胶的制备方法,包括物理交联法、化学交联法、酶交联法、互穿聚合物网络等;概述了海藻酸钠水凝胶在药物释放中的应用,包括口服给药、皮下给药、黏膜给药、肺部给药、经皮给药等;最后讨论了海藻酸钠水凝胶在研究与应用中存在的问题。     

新型羧甲基壳聚糖水凝胶流变性能,药物释放及细胞相容性研究

羧甲基壳聚糖含有丰富的羧基和氨基, 通过1-乙基-(3-二甲基氨基丙基)碳二亚胺盐酸盐(EDC)和N-羟基琥珀酰亚胺(NHS)共催化交联羧甲基壳聚糖形成新型水凝胶. 调节EDC/NHS用量, 制备不同交联度的羧甲基壳聚糖水凝胶(CMCS hydrogels). 研究水凝胶的流变行为, 结果表明, 高交联度的水凝胶具有较好的弹性形变能力, 较高的储存模量, 这是因为随着交联度的升高, 羧甲基壳聚糖水凝胶化学交联网络结构趋于完善. 以胸腺五肽(TP-5)为模型药物, 初步评价CMCS水凝胶药物释放行为, 结果表明水凝胶交联度越高, 胸腺五肽释放速度越慢. MTT法初步评价了水凝胶细胞毒性, 细胞形态和细胞相对增值速率, 结果表明水凝胶毒性很低. 由此可见, 水凝胶具有良好的生物相容性, 在药物缓释和组织工程领域具有广阔的应用前景.     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.     

Facile synthesis of bicyclic 1-arylpyrazol-5-ones

In this Letter, we described a facile method for constructing fused bicyclic 1-arylpyrazol-5-one ring system. We employed various methylene-containing carboxylic acids as the substrates and proved that the pyrazolone ring closure requires activated methylene group in intermediate II. Accordingly, a series of structurally diversified, fused bicyclic 1-arylpyrazol-5-ones was prepared in moderate to high yields using the requisite substrates.     

A carbanion induced synthesis of highly congested pyrazole and imidazole containing heterocycles

An efficient approach to the synthesis of highly congested di, penta and hexacyclic pyrazoles as well as imidazole fragment containing novel heterocyclic molecule has been developed through a carbanion induced transformation of suitably functionalized 2H-pyran-2-ones, benzo[h]chromene and thiochromeno[4,3-b]pyrans. Due to the presence of fluorescence, we report their prime application metal sensor as off/on switching in ferric ions.     

Synthesis of pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles by Curtius reaction in Morita-Baylis-Hillman derivatives

Synthesis of substituted pyrrolo[1,2-a]pyrazines and pyrazino[1,2-a]indoles from the Morita-Baylis-Hillman derivatives of acrylates via saponification followed by Curtius reaction is described.     

正丁胺对激光染料荧光谱影响的研究

用正丁胺作为碳源,采用射频辉光放电制备碳膜,选用激光染料R6G和聚乙二醇混合液作为蒸气源,采用单源热蒸发,在蒸发室与染料同时沉积得到混合膜,用拉曼光谱和红外光谱分析了碳膜的结构和键合方式,分析表明:碳膜中存在胺基团和氢原子.混合膜的荧光谱测量结果表明,认为正丁胺对染料荧光谱的影响是因为胺基和氢原子的存在.     

Selective synthesis of 4,5-dihydroimidazo- and imidazo[1,5-a]quinoxalines via modified Pictet–Spengler reaction

An efficient tandem approach for the selective synthesis of 4,5-dihydroimidazo[1,5-a]quinoxalines 6a–g and imidazo[1,5-a]quinoxalines 7a–h by the reaction of 2-imidazolyl anilines 4a–c with aryl aldehydes 5a–k under mild reaction conditions is described. Introduction of electron releasing alkyl groups in substrates 4a–b was found to be instrumental for the success of the reaction.     

Understanding the Diels-Alder reactivity of 1,2-azaborine analogues

The Diels-Alder reactivity of 1,2-heteroborines (H₄C₄B(H)X, X?=?NH, PH, AsH; O, S, Se) has been computationally explored by means of Density Functional Theory (DFT) calculations. The influence of the HB?=?X fragment on the reactivity of the system has been quantitatively analyzed in detail by means of the so-called Activation Strain Model (ASM) of reactivity. It is found that the interaction between these species and the dienophile is significantly stronger than that computed for their all-carbon isoelectronic counterpart, benzene. In addition, the strain energy plays a key role in the observed reactivity trends. The role of the aromaticity strength of these heteroarenes on the reactivity is also assessed.