Ionization and divalent cation complexation of quinolone antibiotics in aqueous solution

The protonation and divalent cation complexation equilibria of several quin olone antibiotics such as nalidixic acid (NAL), flumequine (FLU), oxolinic acid (OXO), ofloxacin (OFL), norfloxacin (NOR) and enoxacin (ENO) have been examined by potentiometric titration and spectrophotometric method. The an tibacterial activity of these drugs depends upon the pH and the concentrati on of metal cations such as Mg2+, Ca2+ in solution. The apparent ionization constants of NAL, FLU, OXO, OFL, NOR and ENO in aqueous solution were foun d to be 6.33, 6.51, 6.72, 7.18, 7.26, and 7.53, respectively. In aqueous so lution, NAL, FLU and OXO were found to be present mainly as two chemical sp ecies : molecular and anionic; but OFL, NOR and ENO were present mainly as three chemical species : anionic, neutral zwitterionic and cationic form, i n equilibrium. The pK(a1) and pK(a2) are found to be 6.10 and 8.28 for OFL; 6.23 and 8.55 for NOR; 6.32 and 8.62 for ENO, respectively . The complex f ormation constants between OFL, NOR or FLU and some divalent cations are me asured at pH 7.5. The 1 : 1 complexes are formed mainly by ion-dipole inter action. FLU has somewhat larger KF values than OFL and NOR because its mole cular size is small and the FLU is present as anionic form at pH 7.5.