Galan Jhenny F, Brown Jodian, Wildin Jayme L, Liu Zhiwei, Liu Dahui, Moyna Guillermo, Pophristic Vojislava
Center for Drug Design and Delivery and Department of Chemistry & Biochemistry, University of the Sciences in Philadelphia, 600 South 43rd Street, Philadelphia, Pennsylvania 19104-4495, USA.
J Phys Chem B. 2009 Sep 24;113(38):12809-15. doi: 10.1021/jp905261p.
As a part of our systematic study of foldamer structural elements, we analyze and quantify the conformational behavior of two model compounds based on a frequently used class of aromatic oligoamide building blocks. Combining computational and NMR approaches, we investigate ortho-fluoro- and ortho-chloro-N-methylbenzamide. Our results indicate that the -F substituent in an ortho position can be used to fine-tune the rigidity of the oligomer backbone. It provides a measurably attenuated but still considerably strong hydrogen bond (H-bond) to the peptide group proton when compared to the -OCH3 substituent in the same position. On the other hand, the ortho-Cl substituent does not impose significant restrictions on the flexibility of the backbone. Its effect on the final shape of an oligomer is likely governed by its size rather than by noncovalent intramolecular interactions. Furthermore, the effect of solvent on the conformational preferences of these building blocks has been quantified. The number of intramolecularly H-bonded conformations decreases significantly when going from nonprotic to protic environments. This study will facilitate rational design of novel arylamide foldamers.
作为我们对折叠体结构元件进行系统研究的一部分，我们基于一类常用的芳香族寡酰胺构建单元，分析并量化了两种模型化合物的构象行为。结合计算方法和核磁共振方法，我们研究了邻氟-N-甲基苯甲酰胺和邻氯-N-甲基苯甲酰胺。我们的结果表明，邻位的-F取代基可用于微调低聚物主链的刚性。与相同位置的-OCH3取代基相比，它与肽基团质子形成的氢键（H键）强度虽有明显减弱，但仍然相当强。另一方面，邻位-Cl取代基对主链的柔韧性没有显著限制。它对低聚物最终形状的影响可能由其大小而非非共价分子内相互作用决定。此外，还量化了溶剂对这些构建单元构象偏好的影响。从非质子环境转变为质子环境时，分子内形成氢键的构象数量显著减少。这项研究将有助于合理设计新型芳基酰胺折叠体。
