The photochemistry of some fluorinated 7-amino-4-quinolone-3-carboxylic acids used in therapy as antibacterials and known to be phototoxic has been investigated in water. All of them undergo heterolytic defluorination, and this appears to be a path for the generation of aryl cations in solution. 6-Fluoro derivatives such as norfloxacin (Φdec = 0.06) and enoxacin (Φdec = 0.13) give the corresponding phenols. Insertion of an electron-donating substituent makes defluorination inefficient; thus, ofloxacin, an 8-alkoxy derivative, is found to be rather photostable (Φdec = 0.001) and reacts in part via a process different from defluorination (degradation of the N-alkyl side chain). With a 6,8-difluoro derivative, lomefloxacin, the reaction is more efficient (Φ = 0.55) and selective for position 8. Contrary to the previous cases, the aryl cation undergoes insertion in the neighboring N-ethyl group rather than solvent addition (a carbene-like chemistry). With all of the above fluoroquinolones an intensive triplet−triplet absorption is detected and is quenched by sulfite (kq = (1−5) × 108 M-1 s-1). Under this condition, reductive defluorination via the radical anion takes place. The relation of the above chemistry to the phototoxicity of these drugs is commented upon briefly.

Photoinduced C-F bond cleavage in some fluorinated 7-amino-4-quinolone-3-carboxylic acid

FASANI, ELISA;MELLA, MARIELLA;ALBINI, ANGELO
1999

Abstract

The photochemistry of some fluorinated 7-amino-4-quinolone-3-carboxylic acids used in therapy as antibacterials and known to be phototoxic has been investigated in water. All of them undergo heterolytic defluorination, and this appears to be a path for the generation of aryl cations in solution. 6-Fluoro derivatives such as norfloxacin (Φdec = 0.06) and enoxacin (Φdec = 0.13) give the corresponding phenols. Insertion of an electron-donating substituent makes defluorination inefficient; thus, ofloxacin, an 8-alkoxy derivative, is found to be rather photostable (Φdec = 0.001) and reacts in part via a process different from defluorination (degradation of the N-alkyl side chain). With a 6,8-difluoro derivative, lomefloxacin, the reaction is more efficient (Φ = 0.55) and selective for position 8. Contrary to the previous cases, the aryl cation undergoes insertion in the neighboring N-ethyl group rather than solvent addition (a carbene-like chemistry). With all of the above fluoroquinolones an intensive triplet−triplet absorption is detected and is quenched by sulfite (kq = (1−5) × 108 M-1 s-1). Under this condition, reductive defluorination via the radical anion takes place. The relation of the above chemistry to the phototoxicity of these drugs is commented upon briefly.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/106833
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