Di Pietro Maria Enrica, Aroulanda Christie, Merlet Denis, Celebre Giorgio, De Luca Giuseppina
Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria , via P. Bucci, 87036, Arcavacata di Rende, Cosenza, Italy.
J Phys Chem B. 2014 Jul 31;118(30):9007-16. doi: 10.1021/jp505084g. Epub 2014 Jul 17.
The structural and conformational elucidation of flexible bioactive molecules in solution is currently a crucial goal for the scientific community, but it is rarely achievable by available techniques. The anti-inflammatory drug diflunisal is presented here as a model case for supporting the efficiency of NMR spectroscopy combined with the use of weakly ordering media as a promising methodology for the conformational investigation of small bioactive molecules. Starting from NMR anisotropic data (40 independent dipolar couplings), a quite accurate description of its torsional distribution around the inter-ring C-C bond was found, characterized by a pair of two couples of conformers. According to the relative configuration of the carboxylic group and the fluorine atom in the ortho position to the inter-ring C-C bond, the more stable couple of conformers are defined as "trans" type conformers (F opposite to the carboxylic group) whereas the less stable couple are "cis" type conformers (F and carboxylic group on the same side). In order to study the influence of fluorine nuclei on the structure and conformational distribution, the same analytical strategy has been applied to investigate the phenylsalicylic acid, its nonfluorinated analogue.
溶液中柔性生物活性分子的结构和构象解析是目前科学界的一个关键目标，但现有技术很少能实现这一目标。本文以抗炎药二氟尼柳为例，支持将核磁共振波谱与使用弱有序介质相结合作为一种有前景的方法来研究小生物活性分子的构象。从核磁共振各向异性数据（40个独立的偶极耦合）出发，发现了其围绕环间C-C键的扭转分布的相当准确的描述，其特征是有两对构象异构体。根据羧基和与环间C-C键邻位的氟原子的相对构型，较稳定的一对构象异构体被定义为“反式”构象异构体（F与羧基相对），而较不稳定的一对为“顺式”构象异构体（F和羧基在同一侧）。为了研究氟核对结构和构象分布的影响，采用相同的分析策略来研究其非氟化类似物苯基水杨酸。
