Li Rui, Du Tianshu, Liu Jingxing, Aquino Adelia J A, Zhang Jianyu
School of Pharmaceutical Science and Technology, Tianjin University, No. 92 Weijin Road, Naikai District, Tianjin 300072, P. R. China.
Department of Mechanical Engineering, Texas Tech University, Lubbock, Texas 79409, United States.
ACS Omega. 2021 Aug 19;6(34):21952-21959. doi: 10.1021/acsomega.1c02310. eCollection 2021 Aug 31.
Understanding ubiquitous methyl transfer reactions requires a systematic study of thermodynamical parameters that could reveal valuable information about the nature of the chemical bond and the feasibility of those processes. In the present study, the O-CH bond dissociation enthalpies (BDEs) of 67 compounds belonging to phenol/anisole systems were calculated employing the Gaussian-4 (G4) method. Those compounds contain different substituents including alkyl groups, electron-donating groups (EDGs), and electron-withdrawing groups (EWGs). The results show that the bigger branched alkyl groups and EDGs will destabilize the O-CH bond, while EWGs have the opposite effect. A combination of different effects including steric effects, hydrogen bonds, and substituents and their position can achieve around 20 kcal/mol difference compared to the basic phenyl frame. Also, the linear correlation between σ and O-CH BDE can provide a reference for the O-CH BDE prediction. The present study represents a step forward to establish a comprehensive O-CH BDE database to understand the substituent effect and make its contribution to the rational design of inhibitors and drugs.
要理解普遍存在的甲基转移反应，需要对热力学参数进行系统研究，这些参数可以揭示有关化学键性质和这些过程可行性的有价值信息。在本研究中，采用高斯-4（G4）方法计算了属于苯酚/苯甲醚体系的67种化合物的O-CH键解离焓（BDEs）。这些化合物含有不同的取代基，包括烷基、供电子基团（EDGs）和吸电子基团（EWGs）。结果表明，较大的支链烷基和供电子基团会使O-CH键不稳定，而吸电子基团则有相反的效果。与基本的苯基骨架相比，包括空间效应、氢键、取代基及其位置在内的不同效应的组合可以实现约20千卡/摩尔的差异。此外，σ与O-CH BDE之间的线性相关性可为O-CH BDE的预测提供参考。本研究朝着建立一个全面的O-CH BDE数据库迈出了一步，以了解取代基效应，并为抑制剂和药物的合理设计做出贡献。
