Quantum chemical study of penicillin: Reactions after acylation

The density functional theory methods were used on the model molecules of penicillin to determine the possible reactions after their acylation on β‐lactamase, and the results were compared with sulbactam we have studied. The results show that, the acylated‐enzyme tetrahedral intermediate can evolves with opening of β‐lactam ring as well as the thiazole ring; the thiazole ring‐open products may be formed via β‐lactam ring‐open product or from tetrahedral intermediate directly. Those products, in imine or enamine form, can tautomerize via hydrogen migration. In virtue of the water‐assisted, their energy barriers are obviously reduced. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007