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

作　　者：SHABAAN A K Elroby HASSAN A Ewais SAADULLAH G Aziz 

机构地区：[1]Chemistry Department,Faculty of Science,King Abdulaziz University [2]Chemistry Department,Faculty of Science,Beni-Suief University

出　　处：《Chinese Science Bulletin》2012年第14期1665-1671,共7页

基　　金：supported by the Deanship of Scientific Research (DSR)King Abdulaziz University,Jeddah (19/130/1431)

摘　　要：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.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 possi- ble sites in 4-oxo-l,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 stabili- ties 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.

关 键 词：喹诺酮类药物 羟基质子 反应 抗菌化合物 密度泛函理论 电荷密度分布 抗癌药物 结合位点 

分 类 号：O626[理学—有机化学]