Quantum Mechanical Approach for the Catalytic Mechanism of Dinuclear Zinc Metallo-β-lactamase by Penicillin and Cephalexin: Kinetic and Thermodynamic Points of View

Metallo-β-lactamases (mβl) are catalyzing the hydrolytic cleavage of the four-membered β-lactam ring in broad spectrum of antibiotics and therefore inactivating the drug. electronic structure and electronic energy of metallo-β-lactamase active center, two inhibitors of this enzyme including penicillin and cephalexin, and different complexes between these inhibitors and active center of metallo-β-lactamase have been investigated. for both substrates (s), the nucleophilic attack of the amide group substrate to model of active site dinuclear zinc (e) formed an es reactive complex that by passing through the first transition state (ts1), first intermediate (int1), the second intermediate (int2) and second transition state (ts2) converted to the product. also, all thermodynamic functions, δhº, δsº and δgº, are calculated at 25 °c and 1 atm, in order to form two transition states, ts1 and ts2, and also for the total reaction of two mβl inhibitors. in all calculations, solvent effects have been considered in water using pcm method.