Theoretical study of the smiles rearrangement in the activation mechanism of proton pump inhibitors |
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Authors: | Jorge Reyes‐González Rosa María Gómez Fernando Cortés‐Guzmán |
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Institution: | 1. Instituto de Química, Universidad Nacional Autónoma de México, , México, DF 04510 México;2. Centro Conjunto de Investigación en Química Sustentable UAEMex‐UNAM, , Toluca, México, 50200 |
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Abstract: | This work describes the conformational behavior and the activation mechanism of timoprazole and substituted prazoles from the most stable conformation to the sulphenic acid. The stability of the conformers can be explained by the presence of hydrogen bonds, stereoelectronic effect because of the lone pair of sulfur atom and the N…C and N…S interactions. The first step of the Smile rearrangement is a nucleophilic addition to benzimidazole by pyridine moiety, which depends on the difference of the electron population of the atoms involved in the attack. The second step produces sulphenic acid by a concerted reaction where breaking of the S–C bond goes along with a proton migration, and is determined by the electron population of the sulfur atom. Copyright © 2011 John Wiley & Sons, Ltd. |
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Keywords: | activation mechanism conformational analysis omeprazole prazole sulphenic acid |
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