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 (phi 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 (phi 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.
Fasani
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Department of Organic Chemistry, University of Pavia, Italy. fasani@chifis.unipv.it
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Albini
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D000890:Anti-Infective Agents / Q000737:chemistry / Q000528:radiation effects*; D015365:Enoxacin / Q000737:chemistry / Q000528:radiation effects; D024841:Fluoroquinolones; D009643:Norfloxacin / Q000737:chemistry / Q000528:radiation effects; D015242:Ofloxacin / Q000737:chemistry / Q000528:radiation effects; D010782:Photolysis; D017319:Photosensitizing Agents / Q000737:chemistry / Q000528:radiation effects*; D011789:Quantum Theory; D015363:Quinolones / Q000737:chemistry / Q000528:radiation effects; D013329:Structure-Activity Relationship
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D017319:Photosensitizing Agents; D015363:Quinolones; D015365:Enoxacin; D015242:Ofloxacin; C053091:lomefloxacin; D009643:Norfloxacin