School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff, CF10 3AT, UK.
Pharmaceutical Chemistry Department, Hawler Medical University, Erbil, Kurdistan Region, Iraq.
Chemistry. 2020 Mar 23;26(17):3661-3687. doi: 10.1002/chem.201903917. Epub 2020 Jan 20.
The two enantiomers of a compound often have profoundly different biological properties and thus their liability to racemisation in aqueous solutions is an important piece of information. The authors reviewed the available data concerning the process of racemisation in vivo, in the presence of biological molecules (e.g., racemase enzymes, serum albumin, cofactors and derivatives) and under purely chemical but aqueous conditions (acid, base and other aqueous systems). Mechanistic studies are described critically in light of reported kinetic data. The types of experimental measurement that can be used to effectively determine rate constants of racemisation in various conditions are discussed and the data they provide is summarised. The proposed origins of enzymatic racemisation are presented and suggest ways to promote the process that are different from processes taking place in bulk water. Experimental and computational studies that provide understanding and quantitative predictions of racemisation risk are also presented.
该化合物的两种对映异构体通常具有截然不同的生物学特性，因此它们在水溶液中发生外消旋化的倾向是一个重要信息。作者综述了有关外消旋化过程的现有数据，包括体内存在生物分子（如外消旋酶、血清白蛋白、辅因子和衍生物）以及纯化学但水相条件下（酸、碱和其他水体系）的情况。根据报告的动力学数据，对机制研究进行了批判性描述。讨论了可用于在各种条件下有效确定外消旋化速率常数的实验测量类型，并总结了它们提供的数据。提出了酶促外消旋化的起源，并提出了促进该过程的方法，这些方法与在大量水中发生的过程不同。还介绍了提供对外消旋化风险的理解和定量预测的实验和计算研究。
