The transient intermediates in the nanosecond laser flash photolysis of ketoprofen, an aryl propionic acid, show the formation of a carbanion in aqueous solutions at pH 7.1. This carbanion incorporates spectroscopic properties from both a ketyl radical anion and a benzylic radical. The ketoprofen carboxylate undergoes biphotonic photoionization, a process that contributes less than 10% to its photodecomposition and leads to a benzylic-type radical after decarboxylation with a rate constant ≥1 × 107 s-1. On the other hand, the carbanion forms monophotonically and the unsuccessful attempts to sensitize the formation of the ketoprofen triplet excited state in aqueous solutions suggest that the carbanion precursor is either an excited singlet state or an extremely short-lived triplet. In organic solvents of lower polarity, the excited triplet state is readily detectable.

The photochemistry of ketoprofen in aqueous solutions is strongly inÑuenced by its acidÈbase chemistry. While the acid form of ketoprofen behaves as a typical benzophenone chromophore, the ketoprofen carboxylate undergoes efficient photodecarboxylation involving a carbanion intermediate. In the present work we have conducted studies in organic solventÈwater mixtures in attempts to establish the nature of the carbanion precursor. We Ðnd a dual photochemical behavior of ketoprofen depending on the protic state of the ground state absorbing species. The detection of both the ketoprofen triplet and the carbanion during the photolysis of ketoprofen in these mixtures, and the experimentally determined independence of both pathways indicates that the carbanion originates from the singlet state in the system under study.

The fluoroquinolone antibacterial agents possess photosensitizing properties that lead to phototoxic responses in both human and animal subjects. The phototoxicity order reported in humans is: fleroxacin > lomefloxacin, pefloxacin >> ciprofloxacin > enoxacin, norfloxacin and ofloxacin. Studies both in vivo and in vitro have related this phototoxicity to the generation of reactive oxygen species including hydrogen peroxide and the hydroxyl radical. We determined the quantum yields of singlet oxygen generation (phi delta) by detection of the singlet oxygen (1O2) luminescence at 1270 nm for several fluoroquinolones, naphthyridines and other structurally related compounds. All the fluoroquinolones examined have low phi delta values ranging from 0.06 to 0.09 in phosphate buffer at pD 7.5. We also determined the 1O2 quenching constants for these compounds and their values were on the order of 10(6) M-1 s-1, except for lomefloxacin whose rate constant was 1.8 x 10(7) M-1 s-1. The phi delta values were significantly decreased in a solvent of lower polarity such as methanol (0.007 < or = phi delta < or = 0.02). The production of 1O2 by these antibiotics did not correlate with the order reported for their phototoxicity. We also measured the photogeneration (lambda > 300 nm) of superoxide by these antibacterials in dimethylsulfoxide using electron paramagnetic resonance and the spin trap 5,5-dimethyl-1-pyrroline N-oxide. Although there is not a one-to-one correspondence between the relative rates of superoxide generation and the phototoxicity ranking of the fluoroquinolones, the more phototoxic compounds tended to produce superoxide at a faster rate. Nevertheless, the magnitudes of the observed differences do not appear sufficient to explain the range of fluoroquinolone phototoxicity potencies in human and animal subjects in general and the high activity of fleroxacin and lomefloxacin in particular. For these latter drugs the photoinduced loss of the F8 atom as fluoride and the concomitant generation of a highly reactive carbene at C-8 provide a more plausible mechanism for their potent phototoxic and photocarcinogenic properties.