Tautomeric Equilibrium in Condensed Phases.

Abstract

We present an ab initio molecular dynamics (MD) investigation of the tautomeric equilibrium for the aqueous solutions of glycine and acetone under realistic experimental conditions. Metadynamics is used to accelerate proton migration among tautomeric centers. Due to the formation of complex water-ion structures involved in the proton dynamics in the aqueous environment, standard enhanced sampling approaches may face severe limitations in providing a general description of the phenomenon. Recently, we have developed a set of collective variables (CVs) designed to study protons transfer reactions in complex condensed systems [Grifoni, E. Proc. Natl. Acad. Sci. U.S.A. 2019, 116, 4054 4057]. In this work, we applied this approach to study proton dissociation dynamics leading to tautomeric interconversion of biologically and chemically relevant prototypical systems, namely, glycine and acetone in water. Although relatively simple from a chemical point of view, the results show that even for these small systems, complex reaction pathways and nontrivial conversion dynamics are observed. The generality of our method allows obtaining these results without providing any prior information on the dissociation dynamics but only the atomic species that can exchange protons in the process. Our results agree with literature estimates and demonstrate the general applicability of this method in the study of tautomeric reactions.