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.