title: Computer-aided molecular design of solvents for accelerated reaction kinetics.
abstract: Solvents can significantly alter the rates and selectivity of liquid-phase organic reactions, often hindering the development of new synthetic routes or, if chosen wisely, facilitating routes by improving rates and selectivities. To address this challenge, a systematic methodology is proposed that quickly identifies improved reaction solvents by combining quantum mechanical computations of the reaction rate constant in a few solvents with a computer-aided molecular design (CAMD) procedure. The approach allows the identification of a high-performance solvent within a very large set of possible molecules. The validity of our CAMD approach is demonstrated through application to a classical nucleophilic substitution reaction for the study of solvent effects, the Menschutkin reaction. The results were validated successfully by in situ kinetic experiments. A space of 1,341 solvents was explored in silico, but required quantum-mechanical calculations of the rate constant in only nine solvents, and uncovered a solvent that increases the rate constant by 40%.
authors.affiliation: Centre for Process Systems Engineering, Department of Chemical Engineering, Imperial College London, London SW7 2AZ, UK.
authors.forename: Heiko
authors.initials: H
authors.lastname: Struebing
authors.forename: Zara
authors.initials: Z
authors.lastname: Ganase
authors.forename: Panagiotis G
authors.initials: PG
authors.lastname: Karamertzanis
authors.forename: Eirini
authors.initials: E
authors.lastname: Siougkrou
authors.forename: Peter
authors.initials: P
authors.lastname: Haycock
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Piccione
authors.forename: Alan
authors.initials: A
authors.lastname: Armstrong
authors.forename: Amparo
authors.initials: A
authors.lastname: Galindo
authors.forename: Claire S
authors.initials: CS
authors.lastname: Adjiman
mesh_terms: D003198:Computer Simulation; D017076:Computer-Aided Design; D007700:Kinetics; D008956:Models, Chemical; D012997:Solvents / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D012997:Solvents