Enhanced Sampling Simulations on Transition-Metal-Catalyzed Organic Reactions: Zirconocene-Catalyzed Propylene Polymerization and Sharpless Epoxidation

The bond breaking and forming in chemical reactions is a typical rare event, which is one of the difficult problems in molecular dynamics simulations. Numerous enhanced sampling methods have been developed to extend the time scale covered by molecular simulations. However, the difficulties of obtaining appropriate collective variables from complicated reaction pathways and a controlled sampling over the desired phase space remain as challenges. Herein, we use MetaITS, which combines metadynamics and integrated tempered sampling, to increase the sampling efficiency for chemical reactions. Metadynamics with collective variables obtained by harmonic linear discriminant analysis can efficiently decrease the main energy barrier of chemical reaction. Meanwhile, integrated tempered sampling can enhance the exploration of other degrees of freedom. In this study, we applied the MetaITS method to two transition-metal-catalyzed organic reactions with complicated reaction coordinates. We simulated here a zirconocene-catalyzed propylene polymerization to investigate the regioselectivity and temperature effects. We also studied a Sharpless epoxidation reaction, for which both chiral products are observed through simulation.