Photosensitized generation of hydroxyl radical by eight new sulfur and selenium analogs of psoralen

Abstract

Using spin-trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) combined with electron spin resonance spectroscopy (ESR), irradiation at the PUVA wavelength (365 nm) of eight new sulfur and selenium analogs of psoralen was shown to generate hydroxyl radicals (OH ∗), in air-saturated aqueous solution. For each compound, the DMPO-OH spin adduct signal was detected and could be abolished when the photosensitization reaction was carried out in the presence of OH ∗ scavengers such as sodium formate or sodium benzoate. Others inhibitors were selected to investigate the mechanism of OH ∗ generation. A comparison between the different psoralen analogs, psoralen and 8-methoxypsoralen (8-MOP) indicated that the rate of hydroxyl radical production is in the same order or lower than for 8-MOP, except for 7H-thieno (3,2-g) [1] benzothiopyran-7-one which produces 2.7 times more OH ∗ than 8-MOP. Moreover, the presence of superoxide anion (O 2 ∗- as an intermediate, revealed by the effect of superoxide dismutase (SOD) addition on the ESR spectra, was confirmed by following the spectrophotometric reduction of cytochrome c. Laser flash photolysis experiments allowed us to visualize the triplet state of thio- and seleno-psoralens. Because these new psoralen analogs only display a low yield of OH ∗ production, they should be considered as potentially important new drugs to be used in photochemotherapy.