Laboratory for Supramolecular and Nucleoside Chemistry, Ruđer Bošković Institute, P.O.B. 180, HR-10002 Zagreb, Croatia.
Beilstein J Org Chem. 2010 Oct 4;6:945-59. doi: 10.3762/bjoc.6.106.
In this work we report on gelation properties, self-assembly motifs, chirality effects and morphological characteristics of gels formed by chiral retro-dipeptidic gelators in the form of terminal diacids (1a-5a) and their dimethyl ester (1b-5b) and dicarboxamide (1c-5c) derivatives. Terminal free acid retro-dipeptides (S,S)-bis(LeuLeu) 1a, (S,S)-bis(PhgPhg) 3a and (S,S)-bis(PhePhe) 5a showed moderate to excellent gelation of highly polar water/DMSO and water/DMF solvent mixtures. Retro-peptides incorporating different amino acids (S,S)-(LeuPhg) 2a and (S,S)-(PhgLeu) 4a showed no or very weak gelation. Different gelation effectiveness was found for racemic and single enantiomer gelators. The heterochiral (S,R)-1c diastereoisomer is capable of immobilizing up to 10 and 4 times larger volumes of dichloromethane/DMSO and toluene/DMSO solvent mixtures compared to homochiral (S,S)-1c. Based on the results of (1)H NMR, FTIR, CD investigations, molecular modeling and XRPD studies of diasteroisomeric diesters (S,S)-1b/(S,R)-1b and diacids (S,S)-1b/(S,R)-1a, a basic packing model in their gel aggregates is proposed. The intermolecular hydrogen bonding between extended gelator molecules utilizing both, the oxalamide and peptidic units and layered organization were identified as the most likely motifs appearing in the gel aggregates. Molecular modeling studies of (S,S)-1a/(S,R)-1a and (S,S)-1b/(S,R)-1b diasteroisomeric pairs revealed a decisive stereochemical influence yielding distinctly different low energy conformations: those of (S,R)-diastereoisomers with lipophilic i-Bu groups and polar carboxylic acid or ester groups located on the opposite sides of the oxalamide plane resembling bola amphiphilic structures and those of (S,S)-diasteroisomers possessing the same groups located at both sides of the oxalamide plane. Such conformational characteristics were found to strongly influence both, gelator effectiveness and morphological characteristics of gel aggregates.
在这项工作中，我们报告了手性反二肽凝胶剂在末端二酸（1a-5a）及其甲酯（1b-5b）和二羧酸酰胺（1c-5c）衍生物形式下形成的凝胶的胶凝性质、自组装模式、手性效应和形态特征。末端游离酸反二肽（S，S）-双（LeuLeu）1a、（S，S）-双（PhgPhg）3a 和（S，S）-双（PhePhe）5a 表现出对极性较强的水/DMSO 和水/DMF 溶剂混合物的中等至优异的凝胶化作用。含有不同氨基酸的反肽（S，S）-（LeuPhg）2a 和（S，S）-（PhgLeu）4a 没有或只有很弱的凝胶化作用。外消旋和单对映异构体凝胶剂的凝胶化效果不同。手性（S，R）-1c 非对映异构体能够固定高达 10 和 4 倍体积的二氯甲烷/DMSO 和甲苯/DMSO 溶剂混合物，而对映异构体（S，S）-1c 则不能。基于（1）H NMR、FTIR、CD 研究、分子建模和对映异构体二酯（S，S）-1b/（S，R）-1b 和二酸（S，S）-1b/（S，R）-1a 的 X 射线粉末衍射研究的结果，提出了其凝胶聚集体中的基本堆积模型。利用酰胺和肽单元以及层状组织的扩展凝胶分子之间的分子间氢键被确定为出现在凝胶聚集体中的最可能的模式。（S，S）-1a/（S，R）-1a 和（S，S）-1b/（S，R）-1b 对映异构体对的分子建模研究表明，立体化学的影响具有决定性，产生了明显不同的低能量构象：那些具有亲脂性 i-Bu 基团和极性羧酸或酯基团位于酰胺平面相反侧的（S，R）-非对映异构体类似于 bola 两亲结构，而那些具有相同基团位于酰胺平面两侧的（S，S）-非对映异构体。这些构象特征被发现强烈影响凝胶剂的有效性和凝胶聚集体的形态特征。
