title: Theoretical study of the reaction from 6-methylidene penem to seven-membered ring intermediates.
abstract: A sort of beta-lactamase inhibitor, 6-methylidene penem can inhibit both class A and class C serine beta-lactamase. Its inhibition mechanism involves yielding a seven-membered ring intermediate after acylation of the serine. Density functional theory (DFT) method was used on the molecular model to determine the mechanism of producing the seven-membered ring intermediate. Solvent effects were considered via polarizable continuum model (PCM). Moreover, a water-assisted process was considered in the hydrogen transfer process. The results show that the seven-membered ring intermediate can be obtained via two possible mechanisms, namely, concerted mechanism and stepwise mechanism. In stepwise mechanism, a new thiirane intermediate which has never been reported was found. The product of stepwise mechanism, e, has five tautomerics, and they can be tautomerized by hydrogen transfer.
authors.affiliation: Institute of Theoretical Chemistry and College of Life Science, Shandong University, Jinan 250100, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Dacheng
authors.initials: D
authors.lastname: Feng
authors.forename: Maoxia
authors.initials: M
authors.lastname: He
mesh_terms: D000215:Acylation; D002511:Cephalosporins / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006859:Hydrogen / Q000737:chemistry; D008962:Models, Theoretical; D015394:Molecular Structure; D012694:Serine / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D013440:Sulfides / Q000737:chemistry; D013816:Thermodynamics; D014867:Water / Q000737:chemistry; D065093:beta-Lactamase Inhibitors
chemical_list: D002511:Cephalosporins; D004791:Enzyme Inhibitors; D012997:Solvents; D013440:Sulfides; D065093:beta-Lactamase Inhibitors; D014867:Water; D012694:Serine; D006859:Hydrogen; C013523:ethylene sulfide