Photogeneration of Fluoride by the Fluoroquinolone Antimicrobial Agents Lomefloxacin and Fleroxacin

Abstract

The photolysis (> 320 nm) of the fluoroquinolone antibacterial agents lomefloxacin and fleroxacin results in the loss of their F3 atoms as fluoride. The quantum yield for lomefloxacin was 0.98 at pH 7.4. The mechanism probably involves aryl-F heterolysis from the S1 state with the concomitant generation of a carbene at C-8. In contrast, the monofluorinated fluoroquinolones norfloxacin and ciprofloxacin do not generate fluoride upon irradiation. Carbenes are highly reactive species that undergo addition, insertion and abstraction reactions and can cause DNA cleavage. These findings may explain why lomefloxacin and fleroxacin are more photomutagenic and photocarcinogenic than fluoroquinolones in which C-8 is either unsubstituted or bears a substituent other than fluorine.