Theoretical Calculations of β-Lactam Antibiotics. Part VII. Influence of the solvent on the basic hydrolysis of the β-lactam ring |
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Authors: | Juan Frau,Josefa Donoso,Francisco Mu oz,Francisco Gracia-Blanco |
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Affiliation: | Juan Frau,Josefa Donoso,Francisco Muñoz,Francisco Gracia-Blanco |
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Abstract: | We used semi-empirical and ab initio calculations to investigate the nucleophilic attack of the OH? ion on the β-lactam carbonyl group. Both allowed us to detect reaction intermediates pertaining to proton-transfer reactions rather than the studied reaction. We also used the PM3 semi-empirical method to investigate the influence of the solvent on the process. The AMSOL method predicts the occurrence of a potential barrier of 20.7 kcal/mol due to the desolvation of the OH? ion in approaching the β-lactam carbonyl group. Using the supermolecular approach and a H2O solvation sphere of 20 molecules around the solute, the potential barrier is lowered to 17.5 kcal/mol, which is very close to the experimental value (16.7 kcal/mol). |
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