title: Methyl Phosphate Dianion Hydrolysis in Solution Characterized by Path Collective Variables Coupled with DFT-Based Enhanced Sampling Simulations.
abstract: Herein, we propose a conceptually innovative approach to investigating reaction mechanisms. This study demonstrates the importance of considering explicitly the effects of large amplitude motions, aside from the intrinsic reaction coordinate, when tuning the free energy landscape of reaction pathways. We couple the path collective variables method with DFT-based enhanced sampling simulations to characterize the associative mechanism of the hydrolysis of the methyl phosphate dianion in solution. Importantly, energetics and mechanistic differences are observed when passing from the potential to the free energy surface.
authors.affiliation: Department of Drug Discovery and Development, Italian Institute of Technology, Via Morego 30, I-16163 Genoa, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Branduardi
authors.affiliation: Department of Drug Discovery and Development, Italian Institute of Technology, Via Morego 30, I-16163 Genoa, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: De Vivo
authors.affiliation: Dipartimento di Chimica, Università "Federico II", Complesso Universitario di Monte S.Angelo, via Cintia, I-80126 Napoli, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Rega
authors.affiliation: Scuola Normale Superiore, piazza dei Cavalieri 7, I-56126 Pisa, Italy; INFN, Sezione di Pisa, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Barone
authors.affiliation: Department of Drug Discovery and Development, Italian Institute of Technology, Via Morego 30, I-16163 Genoa, Italy.|Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, I-40126 Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cavalli