分子链构象变化对高分子液晶相行为的影响

聚肽高分子溶解在含有机酸的有机溶剂中可以在室温条件下形成液晶．随着温度的下降,体系中的酸分子会引起聚肽分子链发生由刚性螺旋结构向柔性无规线团结构的构象转变．这种转变将导致一个由液晶态向非液晶态的相变．在Ｆｌｏｒｙ格子理论和Ｚｉｍｍ Ｂｒａｇｇ理论的基础上,作者已提出了有关这一现象的理论解释,并通过引入一个与温度有关的库恩链长径比ｘｋ,使理论进一步完善,更切实际地解释聚肽液晶的相行为．此外,还讨论了不同分子刚柔性,不同高分子 溶剂作用系数χ对液晶相行为的影响,以及研究了聚肽液晶的有序参数．     

电场对聚肽液晶相行为的影响

聚合物液晶的相转变不仅可以通过溶液温度或聚合物的浓度的改变来实现,也可以通过施加外电场、磁场等取向场来达到．在二氧六环、氯仿、间甲酚等支持聚肽a一螺旋构象的溶剂中,当PBLG(聚L-谷氨酸γ-苯甲酯)达到一定的浓度会形成胆甾型溶致液晶．对这种液晶施加强度足够     

聚肽的结构性能及其在生物材料领域的应用

聚肽是一类由氨基酸及其衍生物通过聚合反应形成的聚合物，具有和蛋白质类似的二级结构。由于其独特的结构和性能，近年来在蛋白质结构模拟、分子链构象研究、生物医学等领域被广泛地加以研究。本文着重介绍了聚肽的合成、分子链构象、相行为、自组装行为以及在药物缓释等领域的研究和应用状况，并对聚肽在组织工程领域的应用前景进行了展望，为聚肽在生物材料领域的应用提供参考。     

外场对聚肽三元体系相行为影响的研究

在前期建立的溶剂、聚肽、柔性高分子三元体系的理论模型上, 引入外场作用的自由能, 推导了液晶相与非液晶相中各物质的化学位, 研究了外场作用下的聚肽三元体系的相行为. 结果表明外场的作用可使液晶相与非液晶相的两相区域变小, 两相区向低浓度方向移动, 同时柔性高分子可进入液晶相. 此外还研究了外场作用下聚肽的分子链构象、链长和温度等对体系相行为的影响, 并对理论计算与实验结果进行了比较.     

应用分子图形学、分子力学、量子化学及静电势研究农药分子结构与性能的关系(Ⅲ)——一种获得有机分子优势构象的简单方法

通常可采用分子力学计算来得到有机分子的优势构象,但平常使用分子力学程序,由优化分子的构象得到的优化能,往往并不是分子的最低能量,而与分子的最初输入构象有关,是分子的初始输入构象附近的极小值,这给实际应用带来了困难.目前较为常规的求分子最优几何构象的方法是统计方法(Monte Carlo方法),通过模拟退火(The Simulated Annealing)来处理.开始“温度”较高的分子位于能量较高的位置上,这时分子的构象处于少数几个极小区     

链分子的构象弹性理论

研究基于旋转异构态模型、用末端距与构象能描述的链构象分布函数、以及链构象态在体系形变中的消失规则,发展了一个链分子的构象弹性理论.用该理论描述的理想形变行为,支持天然橡胶在大形变时应力陡然上翘归因于链构象变化的观点在物理上的合理性.该理论能够区别不同化学结构高分子所具有的不同形变行为,能够预报高分子形变中熵项与内能项各自的贡献.预报了天然橡胶形变中内能的贡献约为13%, 与实验相符.     

良溶剂中接枝型聚两性电解质单链构象的布朗动力学模拟

采用布朗动力学研究了在良溶剂中荷电平衡的接枝聚两性电解质(GPA)的单链构象转变行为,讨论了主链链长、支链数及电荷密度对GPA分子链构象转变的影响.研究发现,随着静电相互作用的增强,GPA分子链构象转变过程由线团、主链与支链间的折叠、链段塌缩和电荷配对形成偶极子与四极子等4个阶段构成.与线型聚两性电解质不同,GPA存在的额外支链间空间排斥与静电排斥作用随着分子结构的变化而改变,并影响构象转变行为.在强静电相互作用下,良溶剂中的GPA链由于溶剂化作用会再伸展,以保证偶极子完全配对成四极子.减小主链长度或电荷密度或增加支链数目都会增大体系的排斥力和主链的刚性,阻滞分子链的塌缩,并使得分子链再伸展的幅度增大.     

聚肽刚性链/聚氧化丙烯嵌段共聚物的合成与相行为

采用活性阴离子聚合方法,以不同分子量的聚氧化丙烯为引发剂合成了不同分子量的聚（γ－苯甲酯－L－谷氨酸）嵌段共聚物,并用^1H-NMR、IR和偏光显微镜等方法对共聚物进行了表征。结果表明：在1,1,2,2－四氨乙烷中,当溶液浓度一定时,聚（γ－苯甲酯－L－谷氨酸）嵌段共聚物呈现出胆甾型液晶的性质。温度升高时,聚（γ－苯甲酯－L－谷氨酸）共聚物的液晶相溶液发生相转变行为,并且其液晶相稳定性低于相同分子量的聚（γ－苯甲酯－L－谷氨酸）。这与利用Flory-Matheson的构象可变液晶分子理论模型的计算结果相一致。     

溶致凝聚过程中分子链构象的演变

详细讨论了稀溶液、亚浓溶液、浓溶液和极浓溶液中分子链构象的演变,考察了在溶致凝聚过程中分子链的链间相互作用、关联作用和分子链尺寸的变化规律,给出了排除体积的严格定义,引入热关联效应、长程关联效应和全高斯链浓度等概念。指出在不同浓度溶液中,分子链在不同尺度上构象状态不同;在从孤立单链态(良溶液中)向多链聚集态的溶致凝聚过程中,单链的尺寸一直在收缩,由Flory尺寸RF缩小至无扰尺寸R0。这是大分子凝聚过程的一个特点。     

Transitions of Chain＇s Conformation in the Lytropic Condensation of Macromolecules

详细讨论了稀溶液、亚浓溶液、浓溶液和极浓溶液中分子链构象的演变，考察了在溶致凝聚过程中分子链的链间相互作用、关联作用和分子链尺寸的变化规律，给出了排除体积的严格定义，引入热关联效应、长程关联效应和全高斯链浓度等概念。指出在不同浓度溶液中，分子链在不同尺度上构象状态不同；在从孤立单链态（良溶液中）向多链聚集态的溶致凝聚过程中，单链的尺寸一直在收缩，由Flory尺寸RF缩小至无扰尺寸Ro。这是大分子凝聚过程的一个特点。     

The N‐Terminal Nonapeptide of Cephaibols A and C: A Naturally Occurring Example of Mismatched Helical Screw‐Sense Control

The N‐terminal nonapeptide domain of the fungal nonribosomal peptide antibiotics cephaibol A and cephaibol C (AcPheAib₄LeuIvaGly‐ Aib) is reported to adopt a right‐handed helical conformation in the crystalline state. However, this conformation is at odds with the left‐handed helicity observed in solution in related synthetic oligomers capped with Ac‐L ‐PheAib₄ fragments. We report the synthesis of four diastereoisomers of the cephaibol N‐terminal nonapeptide, and show by NMR and CD spectroscopy that the peptide containing the chiral amino acids Phe and Leu in the naturally occurring relative configuration exists in solution as an interconverting mixture of helical screw‐sense conformers. In contrast, the nonapeptide containing the unnatural relative configuration at Phe and Leu adopts a single, stable helical screw‐sense, which is left handed when the N‐terminal Phe residue is L and right‐handed when the N‐terminal Phe residue is D .     

Ambidextrous α,γ‐Hybrid Peptide Foldamers

Molecular chirality is ubiquitous in nature. The natural biopolymers, proteins and DNA, preferred a right‐handed helical bias due to the inherent stereochemistry of the monomer building blocks. Here, we are reporting a rare co‐existence of left‐ and right‐handed helical conformations and helix‐terminating property at the C‐terminus within a single molecule of α,γ‐hybrid peptide foldamers composed of achiral Aib (α‐aminoisobutyric acid) and 3,3‐dimethyl‐substituted γ‐amino acid (Adb; 4‐amino‐3,3‐dimethylbutanoic acid). At the molecular level, the left‐ and right‐handed helical screw sense of α,γ‐hybrid peptides are representing a macroscopic tendril perversion. The pronounced helix‐terminating behaviour of C‐terminal Adb residues was further explored to design helix–Schellman loop mimetics and to study their conformations in solution and single crystals. The stereochemical constraints of dialkyl substitutions on γ‐amino acids showed a marked impact on the folding behaviour of α,γ‐hybrid peptides.     

Folding pentapeptides into left and right handed alpha helices

Left or right handed alpha helicity can be induced in a pentapeptide (ANGYG) by appending left or right handed helical cycles as chiral templates. This sequence corresponds to a rare left handed helix found in the protein alanine racemase. Circular dichroism spectra reveal that pentapeptide ANGYG has no detectable structure in aq phosphate buffer, that it is an ambidextrous peptide in that it can be directed to fold into either a left handed or right handed alpha helix in water, with greater propensity for the uncommon left handed than the normal right handed conformation. A helix-inducing cyclic peptide at both ends of this peptide was more effective at inducing alpha helicity than a single cyclic peptide at one end. The alpha helical cyclic peptides provide novel tools for folding short peptides into thermodynamically unstable helices in water, and for studying factors that control chirality and helix induction.     

Trismaleimide Dendrimers: Helix‐to‐Superhelix Supramolecular Transition Accompanied by White‐Light Emission

Reported here are unprecedented fluorescent superhelices composed of primary, supramolecular polymers of the opposite helical twist. A new class of functional dendrimers was synthesized by amino‐ene click reactions, and they demonstrate an alternating OFF/ON fluorescence with generation growth. A peripherally alkyl‐modified dendrimer displays helix‐sense‐selective supramolecular polymerization, which predominantly forms right‐handed (or left‐handed) helical supramolecular polymers in the solution containing chiral solvents. With increasing the concentration, these primary helical supramolecular polymers spontaneously twist around themselves in the opposite direction to form superhelical structures. Atomic force microscopy and circular dichroism measurements were used to directly observe the helix‐to‐superhelix transition occurring with a reversal in the helical direction. Exceptional white‐light emission was observed during superhelix formation.     

Foldamer‐Mediated Remote Stereocontrol: >1,60 Asymmetric Induction

An N‐terminal L ‐α‐methylvaline dimer induces complete conformational control over the screw sense of an otherwise achiral helical peptide foldamer formed from the achiral quaternary amino acids Aib and Ac₆c. The persistent right‐handed screw‐sense preference of the helix enables remote reactive sites to fall under the influence of the terminal chiral residues, and permits diastereoselective reactions such as alkene hydrogenation or iminium ion addition to take place with 1,16‐, 1,31‐, 1,46‐ and even 1,61‐asymmetric induction. Stereochemical information may be communicated in this way over distances of up to 4 nm.     

alpha and piDL helical states of alternating poly(gamma-benzyl D-L-glutamate) in solution.

As in solid state, strictly alternating poly(gamma-benzyl D-L-glutamate) in solution can adopt two different helical conformations. Besides the alpha helix, a second helical conformation is found at higher temperatures in dioxane and chloroform, the properties of which correspond to that of the piDL4 helix. As the molecules have a finite length a screw sense is favored for both helical forms thus giving rise to optical activity allowing the study of the transconformation by optical rotatory dispersion and circular dichroism besides infrared and dielectric measurements. Thus, as the temperature is raised the equilibria right-left handed alpha helices and alpha-piDL helical forms can be followed. The favored screw senses are determined by the number of interacting side chains for the alpha helix and by the number of hydrogen bonds which are formed in the piDL helical conformation. The side chain-side chain interactions in the alpha helix are experimentally shown to be attractive.     

Controlling the Helix Handedness of ααβ‐Peptide Foldamers through Sequence Shifting

Peptide foldamers containing both cis ‐β‐aminocyclopentanecarboxylic acid and α‐amino acid residues combined in various sequence patterns (ααβ, αααβ, αβααβ, and ααβαααβ) were screened using CD and NMR spectroscopy for the tendency to form helices. ααβ‐Peptides were found to fold into an unprecedented and well‐defined 16/17/15/18/14/17‐helix. By extending the length of the sequence or shifting a fragment of the sequence from one terminus to another in ααβ‐peptides, the balance between left‐handed and right‐handed helix populations present in the solution can be controlled. Engineering of the peptide sequence could lead to compounds with either a strong propensity for the selected helix sense or a mixture of helical conformations of opposite senses.     

A right handed peptide helix containing a central double D-amino acid segment

The crystal structure of the 13 residue peptide Boc-Leu-Aib-Val-Ala-Leu-Aib-Val-DAla-DLeu-Aib-Leu-Aib-Val-OMe reveals a continuous helical conformation providing an unambiguous characterization of contiguous D-residues in a right handed peptide helix.     

The amide-aromatic-ring system : An inherently dissymmetric chromophore

Two cyclic peptide like compounds, cyclo-anthranoyl-L- prolyl (1) and cyclo-homoanthranoyl-L-prolyl (2) have been synthesized and investigated by UV spectroscopy and measurement of circular dichroism. Compound 1 of entirely rigid conformation with two N-CO groups conjugated to the aromatic ring, Ar-NH-CO left handed helical, Ar-CO-N right handed helical, shows a very strong positive Cotton effect centered around 250 nm and a strong negative one centered around 227 nm. Compound 2, which has only one conjugated skewed electron system, Ar-NH-CO, can exist in two different stable conformations, one of them being left handed, the other one right handed helical. It also shows a strong positive Cotton effect centered around 235 nm. Since from earlier ¹³C NMR data the latter was concluded to be the preferred conformation, a right handed helical sense of the amide bond-aromatic ring system is likely to correlate with a positive Cotton effect of this inherently dissymmetric chromophore.     

Control of helical chirality of poly(quinoxaline‐2,3‐diyl)s based on postpolymerization modification of the terminal group by small chiral molecules

Poly(quinoxaline‐2,3‐diyl)s having a terminal formyl or boronyl group were prepared by living polymerization of 1,2‐diisocyanobenzenes using organopalladium initiators bearing a protected formyl or boronyl group. Poly(quinoxaline‐2,3‐diyl)s were successfully deracemized by reacting them with small optically active molecules at their terminal formyl or boronyl group, leading to the induction of optically active helical structures. Poly(quinoxaline‐2,3‐diyl) having terminal formyl groups was converted to one‐handed helical polymer, in which the screw‐sense excess was 68% (84:16). The helix sense of the boronyl‐terminated poly(quinoxaline‐2,3‐diyl) was reversibly controlled by attaching and removing the chiral group. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012