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QM/MM kinetic isotope effects for chloromethane hydrolysis in water
Author(s) -
Javier Ruiz Pernía J.,
Ruggiero Giuseppe D.,
Williams Ian H.
Publication year - 2013
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.3144
Subject(s) - chemistry , chloromethane , kinetic isotope effect , solvation , computational chemistry , molecule , nucleophile , qm/mm , electrophile , kinetic energy , molecular dynamics , deuterium , organic chemistry , atomic physics , physics , quantum mechanics , catalysis
Computational simulations for chloromethane hydrolysis have been performed using hybrid quantum‐mechanical/molecular‐mechanical methods with explicit solvation by large numbers of water molecules. In the first part of the paper, we present results for 2° 2 H 3 , 1° 14 C, and 1° 37 Cl kinetic isotope effects (KIEs) at 298 K with both the AM1/TIP3P and B3LYP/6‐31G* QM methods for the nucleophile H 2 O and electrophile CH 3 Cl surrounded by 496 solvating TIP3P water molecules. An initial Hessian computed for a subset of this system including up to 104 MM water molecules was reduced in size by successive deletion of rows and columns, and KIEs were evaluated for each. We suggest that accurate calculations of KIEs in solvated systems should involve a subset Hessian including the substrate together with any solvent atoms making specific interactions with any isotopically substituted atom. In the second part of the paper, the ensemble‐averaged 2° α‐ 2 H 3 KIE calculated with the B3LYP/6‐31+G(d,p)/TIP3P method is shown to be in good agreement with experiment. This comparison is meaningful because it includes consideration of uncertainties owing to sampling of a range of representative thermally accessible solvent configurations. We also present ensemble‐averaged 14 C and 37 Cl KIEs which have not as yet been determined experimentally. Copyright © 2013 John Wiley & Sons, Ltd.