两亲性多肽自组装及其应用

两亲性多肽分子具有类似天然磷脂分子的两亲特性、丰富的分子结构、独特新颖的组装体结构以及特殊的生物学功能,是多肽自组装研究的热点领域.本文总结了近年来关于两亲性多肽自组装研究及应用的进展,介绍了几种常见的两亲性多肽,并进一步阐述其分子结构特征、组装行为和机理、组装体结构和功能以及在纳米技术和生物医学领域中的应用.     

两亲性嵌段共聚物的合成及其在离子液体中的自组装行为

采用阴离子开环聚合法合成了两亲性嵌段共聚物PLA-PEG-PLA.用FT-IR,1H NMR和GPC等手段对嵌段共聚物的结构组成进行了表征.两亲性嵌段共聚物在离子液体1-丁基-3-甲基咪唑六氟磷酸盐中能自组装成胶束,用透射电子显微镜观察了聚合物在离子液体中形成胶束的纳米结构.当疏水链长固定时,胶束的自组装形状主要依赖于亲水链的长度.两亲性共聚物在离子液体中可自组装成可控制结构的纳米胶束,这种纳米结构胶束在很多领域具有广泛的应用前景.     

两亲性共轭高分子聚(对亚苯基丁二炔)的合成与二维自组装

设计、合成了两亲性线型共轭聚合物聚(对亚苯基丁二炔)(A-PPB),研究了它在溶液中的二维自组装行为.首先合成了A-PPB的前驱体聚合物PPB,利用核磁氢谱(1H-NMR)、傅里叶红外光谱(FTIR)和拉曼光谱对聚合物的结构及分子量进行了表征.然后通过水解反应,获得了两亲性共轭聚合物A-PPB,并考察了它在水、甲醇以及甲醇/甲苯混合溶剂中的自组装行为.透射电子显微镜(TEM)的测试结果表明,A-PPB在水溶液中自组装形成了二维超分子纳米片(2D-SNS),尺寸达几微米;用原子力显微镜(AFM)测得2D-SNS的厚度为5 nm左右,由不超过3层的二维超分子聚合物层堆积而成.高分辨透射电子显微镜(HRTEM)、选区电子衍射(SAED)及X-射线衍射(XRD)的测试结果表明,2D-SNS是由A-PPB分子链平行堆积而成.在甲醇溶剂中,A-PPB形成了无规聚集体,而在甲醇/甲苯混合溶剂中则自组装形成了多层堆积的二维超分子纳米片.对比研究表明,非亲水的PPB在氯仿/甲醇混合溶剂中形成的是较厚的层状聚集体.还发现聚合物的链长对于自组装形成二维超分子片层也会有影响,当用数均聚合度为8的两亲性低聚(对亚苯基丁二炔)(A-OPB)在水溶液中进行自组装时,只能形成尺寸较小的无规聚集体.由此可见,聚合物的两亲性、电荷排斥作用以及聚合物链长等因素都会对共轭聚合物的二维自组装行为产生重要影响.     

无规共聚物自组装球形胶束表面亲水性的耗散粒子动力学模拟

建立了含不同亲疏水粒子比的双亲性无规共聚物粗粒化模型. 采用耗散粒子动力学方法模拟了两亲性无规共聚物选择性溶剂自组装球形胶束表面的亲水性能. 模拟结果表明, 无规共聚物在选择性溶剂中自组装得到实心球形胶束, 球形胶束表面的亲水性与聚合物链亲水粒子含量、溶剂的选择性有关. 随着聚合物链所含亲水粒子增加, 球形胶束表面的亲水性增强. 球形胶束表面的亲水性随着疏水粒子与溶剂粒子间的排斥参数增大而增强, 模拟结果与实验结论一致. 该模拟方法给出的胶束微结构信息可以为双亲无规共聚物分子设计及自组装双亲胶束制备提供一定的理论指导.     

新型仿生聚合物胶束用于纳米药物载体的研究

对两亲性聚合物进行设计和优化, 从细胞膜仿生的设计出发, 利用原子转移自由基聚合, 制备了一种以胆固醇为疏水段、以仿细胞膜磷酸胆碱基聚合物为亲水段的两亲性分子CMPC. 在对其溶液胶束自组装行为进行探索的基础上, 以水包油(O/W)溶剂挥发法制备了包含抗癌药物阿霉素(ADR)的纳米抗癌药物载体, 通过体外细胞培养, 研究了仿细胞膜两亲分子的细胞相容性, 并对抗癌纳米药物载体抗肿瘤细胞的药效进行了初步研究.     

偶氮苯基两亲性聚合物的自组装行为研究进展

偶氮苯基两亲性聚合物结合了偶氮苯基团的光响应、酶响应、主客体识别特性和两亲性聚合物的自组装特性,能够在选择性溶剂中发生聚合物可控自组装行为,这使得其在药物控释、纳米技术和生物医学材料等领域受到了广泛的关注。本文从结构类型和合成方法出发,综述了新型偶氮苯基两亲性聚合物在溶液中的自组装研究进展,并对该领域的发展前景进行了展望。     

基于桑蚕丝蛋白的多肽/两亲性多肽及其组装和功能化

多肽的自组装因其独特性质和作用已成为超分子化学、高分子功能材料和生物医用材料等领域的研究热点.桑蚕丝蛋白具有高度重复的多肽序列,其组装行为和相应的结构对动物丝及丝蛋白基材料的形成和特有的优异综合性能起到了至关重要的作用.通过特定的酶降解桑蚕丝蛋白能够以较为经济的方式获得多种明确序列的多肽,并可进一步方便地制备功能性的两亲性多肽.本文结合国内外多肽自组装的研究现状,对本课题组在桑蚕丝蛋白多肽/两亲性多肽的制备、组装以及功能化等方面的研究成果进行了总结,同时也展望了其在若干领域中的实际应用.     

分子自组装单层膜的表面浸润性研究现状和展望

立足于分子自组装单层膜的制备及结构, 讨论了分子自组装单层膜的头基基团与基底的作用机理、 主链与环境的温度依赖关系, 特别是其端基基团的化学性质及构象对表面浸润行为的影响. 重点讨论了分子自组装单层膜的端甲基基团对表面能的贡献、 极性端基基团与水分子之间的相互作用以及自组装单层膜表面的分子尺寸粗糙度对表面浸润的影响. 最后, 基于理论和实验基础对以上问题提出新的认知与看法, 并对未来该领域发展的机遇与挑战进行了展望.     

杂臂星型嵌段共聚物在溶液中自组装形成囊泡结构的计算机模拟

利用耗散粒子动力学模拟方法, 研究了杂臂星型嵌段共聚物A_m(B_n)₂在溶液中自组装形成囊泡的行为. 主要分析了自组装过程、亲水分枝和疏水分枝的长度及分子构型对组装结构的影响. 结果表明, 杂臂星型聚合物在溶液中会自组装形成碟状胶束, 之后弯曲闭合形成囊泡. 当亲水部分的分枝较短时, 易于形成囊泡结构; 在可形成囊泡结构的条件下, 双分子层囊泡膜的厚度随分枝长度的增加而增加. 与构成相近的线型嵌段共聚物相比, 杂臂星型嵌段共聚物更易形成囊泡结构, 且形成的囊泡结构较薄.     

合成双分子膜的研究（Ⅱ）：HBBTAB的合成及其在水溶液中的自组织行为

1977年Kunitake等首次报道了双十二烷基二甲基溴化铵在水溶液中自组织成类似于卵磷脂双层结构的囊泡,泡壁即为双分子膜。该发现表明可以用人工合成方法建造仿生组织,开辟了合成双分子膜研究的新领域。单链两亲性成膜物质,一般由亲水基团、间链、刚性生色基和尾链4部分组成。本文报道4-(4′-十六烷氧基-4-联苯氧基)丁基三甲基溴化铵     

Aqueous self-assembly of aromatic rod building blocks

One of the most fascinating subjects in areas such as nanoscience and biomimetic chemistry is concerned with the construction of novel supramolecular nanoscopic architectures with well defined shapes and functions. Supramolecular assemblies of aromatic rod molecules provide a facile entry into this area. Aromatic rigid rod molecules consisting of hydrophilic flexible chains, in aqueous solution can self-assemble into a variety of supramolecular structures through mutual interactions between aromatic rod molecules and water, including hydrophobic and hydrophilic interactions and pi-pi interaction. The supramolecular architecture in water can be manipulated by variation of the shape of the rigid segments, as well as the relative volume fraction of the flexible segment. The rigid aromatic segments have significant photonic and electronic properties. The self-assembly of aromatic rod molecules in water, therefore, can provide a strategy for the construction of well-defined and stable nanometer-size structures with chemical functionalities and physical properties as advanced materials for photonic, electronic and biological applications.     

Progress in the direct structural characterization of fibrous amphiphilic supramolecular assemblies in solution by transmission electron microscopic techniques

The self-assembly of amphiphilic molecules into fibrous structures has been the subject of numerous studies over past decades due to various current and promising technical applications. Although very different in their head group chemistry many natural as well as synthetic amphiphilic compounds derived from carbohydrates, carbocyanine dyes, or amino acids tend to form fibrous structures by molecular self-assembly in water predominantly twisted ribbons or tubes. Often a transition between these assembly structures is observed, which is a phenomenon already theoretically approached by Wolfgang Helfrich and still focus point in current research. With the development of suitable sample preparation and electron optical imaging techniques, cryogenic transmission electron microscopy (cryo-TEM) in combination with three-dimensional (3D) reconstruction techniques has become a particular popular direct characterization technique for supramolecular assemblies in general. Here we review the recent progress in deriving precise structural information from cryo-TEM data of particularly fibrous structures preferably in three dimensions.     

Assembling of amphiphilic highly branched molecules in supramolecular nanofibers

We found that the amplification of weak multiple interactions between numerous peripheral branches of irregular, flexible, polydisperse, and highly branched molecules can facilitate their self-assembly into nanofibrillar micellar structures at solid surfaces and the formation of perfect long microfibers in the course of crystallization from solution. The core-shell architecture of the amphiphilic dendritic molecules provides exceptional stability of one-dimensional nanofibrillar structures. The critical condition for the formation of the nanofibrillar structures is the presence of both alkyl tails in the outer shell and amine groups in the core/inner shell. The multiple intermolecular hydrogen bonding and polar interactions between flexible cores stabilize these nanofibers and make them robust albeit flexible. This example demonstrates that one-dimensional supramolecular assembling at different spatial scales (both nanofibers and microfibers) can be achieved without a tedious, multistep synthesis of shape-persistent molecules.     

The molecular basis of self-assembly of dendron-rod-coils into one-dimensional nanostructures

We describe here a comprehensive study of solution and solid-state properties of self-assembling triblock molecules composed of a hydrophilic dendron covalently linked to an aromatic rigid rod segment, which is in turn connected to a hydrophobic flexible coil. These dendron-rod-coil (DRC) molecules form well-defined supramolecular structures that possess a ribbonlike morphology as revealed by transmission-electron and atomic-force microscopy. In a large variety of aprotic solvents, the DRC ribbons create stable networks that form gels at concentrations as low as 0.2% by weight DRC. The gels are thermally irreversible and do not melt at elevated temperatures, indicating high stability as a result of strong noncovalent interactions among DRC molecules. NMR experiments show that the strong interactions leading to aggregation involve mainly the dendron and rodlike blocks, whereas oligoisoprene coil segments remain solvated after gelation. Small-angle X-ray scattering (SAXS) profiles of different DRC molecules demonstrate an excellent correlation between the degree-of-order in the solid-state and the stability of gels. Studies on two series of analogous molecules suggest that self-assembly is very sensitive to subtle structural changes and requires the presence of at least four hydroxyl groups in the dendron, two biphenyl units in the rod, and a coil segment with a size comparable to that of the rodlike block. A detailed analysis of crystal structures of model compounds revealed the formation of stable one-dimensional structures that involve two types of noncovalent interactions, aromatic pi-pi stacking and hydrogen bonding. Most importantly, the crystal structure of the rod-dendron compound shows that hydrogen bonding not only drives the formation of head-to-head cyclic structures, but also generates multiple linkages between them along the stacking direction. The cyclic structures are tetrameric in nature and stack into ribbonlike objects. We believe that DRC molecules utilize the same arrangement of hydrogen bonds and stacking of aromatic blocks observed in the crystals, explaining the exceptional stability of the nanostructures in extremely dilute solutions as well the thermal stability of the gels they form. This study provides mechanistic insights on self-assembly of triblock molecules, and unveils general strategies to create well-defined one-dimensional supramolecular objects.     

氮杂芳基三脚架配体及其金属超分子化合物

氮杂芳基三脚架配体可分为柔性和刚性两种，它们均有三个或三个以上的配位点，配体中配位点数目和位置的改变都会对金属超分子配合物的结构产生很大的影响。本文简单介绍了氮杂芳基三脚架配体自组装的特点及其所生成的超分子化合物的主要结构类型。     

Supramolecular polymeric micelles by the host-guest interaction of star-like calix[4]arene and chlorin e6 for photodynamic therapy

A supramolecular drug delivery system has been developed via the self-assembly of a supramolecular amphiphilic polymer, which is constructed by the host-guest interaction of hydrophilic PEGylated calix[4]arene and hydrophobic photosensitizer chlorin e6. It provides a new strategy for the preparation of supramolecular polymeric micelles, and plays an important role in biological applications.     

Host-guest supramolecular chemistry at solid-liquid interface: An important strategy for preparing two-dimensional functional nanostructures

Supramolecular self-assembly,an important strategy in nanotechnology,has been widely studied in the past two decades.In this review,we have introduced the recent progress on construction of two-dimensional(2D)nanostructures by host-guest supramolecular chemistry at solid-liquid interface,and the interactions between the host assembly and the guest molecules are the major concerns.At first,the hydrogen bonds connected hybrid structures are discussed.And then we have paid a close attention on the surface-confined condensation reactions that has flourished recently in direct preparing novel nanostructures with increasing structural complexity.In the end,the cavity confinement of the 2D supramolecular host-guest architectures has been studied.On the basis of the above-mentioned interactions,a group of functional hybrid structures have been prepared.Notably,scanning tunneling microscopy(STM),a unique technique to probe the surface morphology and information at the single molecule level,has been used to probe the formed structures on highly oriented pyrolytic graphite(HOPG)surface.     

Supramolecular reactor from self-assembly of rod-coil molecule in aqueous environment

We synthesized an amphiphilic coil-rod-coil triblock molecule consisting of hexa-p-phenylene as a rod block and poly(ethylene oxide) with the number of repeating units of 17 as coil blocks and investigated aggregation behavior in aqueous environment. The rod-coil molecule was observed to aggregate into discrete micelles consisting of hydrophobic disklike rod bundles encapsulated by hydrophilic poly(ethylene oxide) coils. The aromatic bundles of the micelles were demonstrated to be used as an efficient supramolecular reactor for the room temperature Suzuki cross-coupling reaction of a wide range of aryl halides, including even aryl chlorides with phenylboronic acids in aqueous environment. These results demonstrate that self-assembly of amphiphilic rod-coil molecules can provide a useful strategy to construct an efficient supramolecular reactor for aromatic coupling reaction.     

Synthesis and self-assembly of oligomers containing cruciform 9,10-bis(arylethynyl)anthracene unit: formation of supramolecular nanostructures based on rod-length-dependent organization

Conjugated rod-coil molecules, incorporating flexible and rigid blocks, have a strong affinity to self-organize into various supramolecular nanostructures in the bulk state.In this study, we report synthesized oligomers containing cruciform 9,10-bis(arylethynyl)anthracene units and characterized their self-assembly behavior. The molecular structures were characterized with ¹H, ¹³C NMR, and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectroscopy. An investigation of the supramolecular nanostructures of these molecules using differential scanning calorimetry, thermal polarized optical microscopy, and small-angle X-ray scattering revealed that the rod length of coil-rod-coil molecules with identical rod to coil volume ratios dramatically influences self-assembly behavior in the bulk state. Molecules 2 and 3 with relatively longer rod lengths self-assemble into lamellar structures in the solid state, whereas, molecules 1 and 4 self-assemble into two-dimensional (2-D) oblique columnar structures in the liquid crystalline phase, in addition, on heating, molecule 1 transforms from the oblique columnar phase to the nematic phase.     

Supramolecular self-assembly of block copolymer based on rigid surfactant

The supramolecular self-assembling of pyridine-containing amphiphilic block copolymers (PS-b- P4VP and PS-PI-P2VP) and 4-biphenylcarboxylic acid (BPCA) in selective solvents has been systematically studied. BPCA molecules are able to complex with the vinylpyridine (VP) moieties through hydrogen bonding, which leads to a transformation of spherical block copolymer micelles into structured nanofibers in solutions. The effects of molar ratio of BPCA to the VP repeat units, solvent selectivity, and copolymer composition on the supramolecular complex nanofiber formation have been systematically investigated by atomic force microscopy (AFM), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The formation mechanism of supramolecular self-assembly nanofibers was discussed.