PHOTOCHEMISTRY OF 2-MERCAPTOPYRIDINES .3. EPR STUDY OF PHOTOPRODUCTION OF HYDROXYL RADICALS BY N-HYDROXYPYRIDINE-2-THIONE USING 5,5-DIMETHYL-1-PYRROLINE N-OXIDE IN AQUEOUS-SOLUTIONS

N-Hydroxypyridine-2-thione, 2-S-PyrNOH, a potent antimicrobial, antifu ngal and anticancer agent, is photochemically active and upon UV irrad iation generates free radicals. We have employed EPR and the spin-trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) to investigate the photochemi stry in aqueous solutions of 2-S-PyrNOH (used here in the form of a so dium salt, 2-S-PyrNONa). We found that upon photoactivation 2-S-PyrNON a can follow two different pathways: it can produce hydroxyl radicals and/or it can act as a photoreducing agent. The capacity of 2-S-PyrNON a to produce (OH)-O-. radicals has been demonstrated by: (1) EPR detec tion of the DMPO/(OH)-O-. adduct in UV-irradiated samples; (2) inhibit ion of the DMPO/(OH)-O-. formation by (OH)-O-. scavengers such as meth yl alcohol, formate and DMSO and (3) by detection of EPR signals of DM PO adducts with radicals derived from reaction of (OH)-O-. with these inhibitors. The photoreductive capacity of 2-S-PyrNONa was deduced fro m the observation that the amplitude of the EPR signal of the spin add uct DMPO/(OH)-O-. decreased on UV irradiation in air-free pH 7.0 buffe rs and that the signal recovered in the dark and after aeration. The a bility to generate free radicals upon UV irradiation suggests that 2-S -PyrNONa can be regarded as a potential photocytotoxic agent. This fea ture may be relevant to the biological action of this compound. Our fi ndings also emphasize that caution should be used when 2-S-PyrNOH is e mployed as a source of (OH)-O-. radicals in biological or chemical sys tems.