Development of a True Transition State Force Field from Quantum Mechanical Calculations

Transition
state force fields (TSFF) treated the TS structure as an artificial
minimum on the potential energy surface in the past decades. The necessary
parameters were developed either manually or by the Quantum-to-molecular
mechanics method (Q2MM). In contrast with these approaches, here we
propose to model the TS structures as genuine saddle points at the molecular
mechanics level. Different methods were tested on small
model systems of general chemical reactions such as protonation, nucleophilic
attack, and substitution, and the new procedure led to more accurate
models than the Q2MM-type parametrization. To demonstrate the practicality
of our approach, transferrable parameters have been developed for
Mo-catalyzed olefin metathesis using quantum mechanical properties
as reference data. Based on the proposed strategy, any force field
can be extended with true transition state force field (TTSFF) parameters,
and they can be readily applied in several molecular mechanics programs
as well.

过渡态势力场（Transition State Force Fields，TSFF）在过去数十年间，均将过渡态结构视为势能面上的人工极小值点。其所需参数多通过手动方式，或借助量子-分子力学方法（Quantum-to-molecular mechanics method，Q2MM）进行开发。与上述传统方法不同，本文提出在分子力学层面将过渡态结构建模为真实鞍点。我们针对质子化、亲核进攻、取代等典型化学反应的小型模型体系测试了多种方法，结果显示，相较于Q2MM类参数化方案，本新方法可得到精度更优异的模型。为验证本方法的实用性，我们以量子力学性质作为参考数据，为钼催化的烯烃复分解反应开发了可迁移参数。基于所提出的策略，任意力场均可通过添加真实过渡态势力场（True Transition State Force Field，TTSFF）参数进行拓展，且此类参数可直接应用于多款分子力学程序中。