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Cover Image, Volume 33, Issue 24
Publication year - 2012
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Reports
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.22079
Subject(s) - nucleophile , cover (algebra) , molecule , chemistry , carboxylate , density functional theory , aqueous solution , gas phase , ab initio , computational chemistry , stereochemistry , organic chemistry , catalysis , mechanical engineering , engineering
A theoretical study of the hydrolysis of a b‐lactam antibiotic, cefotaxime (CEF), in gas phase with semi‐empirical and density functional theory (DFT) methods, and in aqueous solution by means of hybrid quantum mechanics/molecular mechanics (QM/MM) potentials, is presented on page 1948 by Conchín Meliá, Silvia Ferrer, Vicent Moliner, Iñaki Tuñón, and Juan Bertrán. The inclusion of the full molecule of the CEF in the gas phase molecular model has been demonstrated to be crucial since its carboxylate group can activate the nucleophilic water molecule. In aqueous solution, the free energy profiles show a step‐wise mechanism that is kinetically determined by the nucleophilic attack of a water molecule which, in turn, can be activated by a proton transfer from the carboxylate group of the substrate (the first step). The image represents the molecule of CEF and the water molecule that hydrolizes the b‐lactam ring.