The ab initio study and NBO interpretation of solvent effects on the structural stability and the chemical reactivity of penicillin-V conformations

Quantum mechanics (QM) methods were used to examine the electronic structure and the relative stability of penicillin-V (PV) conformations in the gas phase and the different solvent media. The effects of solvent dielectric constant and the computational methods were analyzed on the conformational stability of beta-lactam-thiazolidine bicyclic system, its geometry and its reactivity. Our findings indicated that in the PV, the axial form of thiazolidine ring is more stable than equatorial form one in all of the tested media. This is in agreement with the NMR studies performed on PV that indicate the axial conformation is the dominant form in solid state. Furthermore, the atomic charges computations and natural bond orbital Interpretation (NBO) represented that by increasing the solvent dielectric constant, the charge values on the C-5 and C-7 atoms of the beta-lactam ring decrease, while HOMO-LUMO gap and occupancy values of the contained bonds in b-lactam ring of the interested structures increase. Hence, the b-lactam ring possesses the lowest reactivity against nucleophilic attacks and the highest stability in presence of implicit waters. However, it can be concluded that the structural stability of penicillin-V conformations is controlled by solvent's polarity and its dielectric constant, the electrophilic nature of beta-lactam ring and HOMO-LUMO gap. (C) 2014 Production and hosting by Elsevier B.V. on behalf of King Saud University.