Publication details

Title	Computer-aided molecular design of solvents for accelerated reaction kinetics
Document Type	Article
Year	2013
Authors	Struebing, H., Ganase, Z., Karamertzanis, P.G., Siougkrou, E., Haycock, P., Piccione, P.M., Armstrong, A., Galindo, A., Adjiman, C.S.
Source	Nature Chemistry, vol.5, no.11, p.952-957
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%. © 2013 Macmillan Publishers Limited. All rights reserved. More info Publication link
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