Effects of protonation and deprotonation on the reactivity of quinolone: A theoretical study

Quinolones are the subject of much research as antibacterial compounds and as a new class of antitumor agents. The protonation (P) and deprotonation (D) sites and conformations of quinolone were investigated. The proton affinity (PA) on each of the possible sites in 4-oxo-1,4-dihydroquinoline has been calculated by the restricted Hartree-Fock (HF) and density functional theory (DFT) methods with the basis set 6-311G**. The O-site of protonation was found to be strongly favored over the N-site for the studied compound in the gas phase. Deprotonation takes place in quinolone by detachment of the N-H and COOH protons. The PA of the simple quinolone molecule was used to characterize quinolone reactivity with DNA binding sites. The relative stabilities of the syn and anti conformations were investigated at the B3LYP/6-311G** level of theory; the syn form was shown to be slightly more stable. Its conformation seems to be intrastabilized by hydrogen-bonds consisting of a hydroxyl proton with the O10 atom as the acceptor. We computed and discussed the charge-density distribution and electrostatic potential to explain the reactivity of quinolone.