Electronic structure and physicochemical properties of selected penicillins

Abstract Traditionally, penicillins have been used as antibacterial agents due to their characteristics and widespread applications with few collateral effects, which have motivated several theoretical and experimental studies. Despite the latter, their mechanism of biological action has not been completely elucidated. We present a theoretical study at the Hartree–Fock and density functional theory (DFT) levels of theory of a selected group of penicillins such as the penicillin‐G, amoxicillin, ampicillin, dicloxacillin, and carbenicillin molecules, to systematically determine the electron structure of full β‐lactam antibiotics. Our results allow us to analyze the electronic properties of the pharmacophore group, the aminoacyl side‐chain, and the influence of the substituents (R and X) attached to the aminoacyl side‐chain at 6′ (in contrast with previous studies focused at the 3′ substituents), and to corroborate the results of previous studies performed at the semiempirical level, solely on the β‐lactam ring of penicillins. Besides, several density descriptors are determined with the purpose of analyzing their link to the antibacterial activity of these penicillin compounds. Our results for the atomic charges (fitted to the electrostatic potential), the bond orders, and several global reactivity descriptors, such as the dipole moments, ionization potential, hardness, and the electrophilicity index, led us to characterize: the active sites, the effect of the electron‐attracting substituent properties and their physicochemical features, which altogether, might be important to understand the biological activity of these type of molecules. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007