STRUCTURE AND MEDIUM-DEPENDENT PHOTODECOMPOSITION OF FLUOROQUINOLONE ANTIBIOTICS

The photochemical reactivity of four fluoroquinolone antibiotics is ex amined. For norfloxacin (NOR), enoxacin (ENX) and lomefloxacin (LOM), the only process occurring is defluorination (from position 6 for the first two drugs, from position 8 for the last one). The quantum effici ency is both structure and medium dependent (Phi close to 0.5 both in water and in 0.1 M phosphate buffer for LOM; 0.01 for ENX and 0.004 fo r NOR in buffer, but more than an order of magnitude higher in neat wa ter). Ofloxacin (OFL) is less light sensitive (Phi 0.001) and undergoe s, in part, reactions different from defluorination. The photoreaction involves heterolytic C-F bond fragmentation and its efficiency is det ermined by the internal charge-transfer character of the excited state (increasing in the series OFL < NOR < ENX < LOM according to the elec tronegativity of the substituent in position 8) and by the stabilizati on of the resulting aryl cation (larger for the 8-cation than for the 6-cation), The relevance of these data for the rationalization of the known phototoxicity of these drugs is discussed.