Refined metadynamics through canonical sampling using time-invariant bias potential; A Study of polyalcohol dehydration in hot acidic solutions

Kondo, Tomomi ; Sasaki, Takehiko*; Ruiz-Barragan, S.*; Ribas-Ario, J.*; Shiga, Motoyuki   ; Ruiz-Barragan, S.*

We propose a canonical sampling method to refine metadynamics simulations a posteriori. This approach could be useful particularly when two or more free energy barriers are to be compared among chemical reactions in different or competing conditions. The method was then applied to study the acid dependence of polyalcohol dehydration reactions in high-temperature aqueous solutions. It was found that the reaction proceeds consistently via an S2 mechanism, whereby the free energy of protonation of the hydroxyl group created as an intermediate is affected significantly by the acidic species.