Structure and medium - dependent photodecomposition of fluoroquinolone antibiotics

The photochemical reactivity of four fluoroquinolone antibiotics is examined. 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 efficiency is both structure and medium dependent (4 close to 0.5 both in water and in 0.1 M phosphate buffer for LOM,- 0.01 for ENX and 0.004 for NOR in buffer, but more than an order of magnitude higher in neat water). Ofloxacin (OFL) is less light sensitive φ 0.001) and undergoes, in part, reactions different from defluorination. The photoreaction involves heterolytic C-F bond fragmentation and its efficiency is determined by the internal charge-transfer character of the excited state (increasing in the series OFL < NOR < ENX < LOM according to the electronegativity of the substituent in position 8) and by the stabilization 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.