Theoretical Study of the Hydrolysis Mechanism of Β -Lactam Antibiotics Catalysed by a Zn(II) Dinuclear Biomimetic Organometallic Complex

The degradation and metabolism of antibiotics have attracted the scientific community's attention due to the environmental problems caused by the inappropriate use and disposal of these drugs. Therefore, it is crucial to understand the reaction mechanism involved in the degradation of these compounds. We studied the hydrolysis of nitrocefin and benzylpenicillin, two beta-lactam ring antibiotics, mediated by an enzymatic mimetic Zn organometallic compound, using DFT methods. The electronic effects of functional groups adjacent to the beta-lactam ring were analysed and good agreement between experimental and theoretical results was found. The reaction involves the nucleophilic attack of the bridging hydroxide group on the Zn atoms towards the beta-lactam ring. A stepwise mechanism was found to agree with the experimental results. Chemical hardness profiles were affected by the solvent and reaction synchronicity. Geometric rearrangements dominated the activation barrier, and both antibiotics exhibited late transition states.