Unusual singlet oxygen-dependent hydroxyl radical production by a unique ruthenium-polypyridyl-hydroxamate complex under visible light irradiation†

Ruthenium polypyridyl complexes have been widely used in photodynamic therapy, during which singlet oxygen (¹O₂) plays a crucial role. Here, we synthesized a unique Ru complex Ru(bpy)₂PhenHA (bpy – bipyridine, Phen – 1,10-phenanthroline, HA – hydroxamic acid) and unexpectedly found that not only ¹O₂, but also reactive hydroxyl radical (˙OH) could be produced under visible-light irradiation of Ru(bpy)₂PhenHA in the presence of a classic spin trapping agent, 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Analogous ˙OH production was also observed with 3,3,5,5-tetramethyl-1-pyrroline-N-oxide (TMPO), but not with other spin trapping agents. In contrast, much less ˙OH was produced when substituting Ru(bpy)₂PhenHA with Ru(bpy)₂Phen lacking the HA group. However, when N-methyl-benzohydroxamic acid (a typical HA with reducing properties) was added into the DMPO/Ru(bpy)₂Phen/VIS system, not only ˙OH, but also the corresponding secondary nitroxide radical was clearly detected. Similar results were also observed with other structurally-different reducing agents. Further studies with other known spin trapping agents suggest that the [DMPO–OOH]˙ intermediate might be transiently produced and then rapidly decomposed to produce ˙OH. Taken together, the molecular mechanism for the unusual ˙OH production was proposed: visible-light irradiation of Ru(bpy)₂PhenHA produced ¹O₂, which electrophilically added on DMPO, forming a peroxide intermediate, which then quickly decomposed to a biradical [DMPO–OO]˙˙. Then, H-abstraction took place between [DMPO–OO]˙˙ and the reducing hydroxamic acid, forming the unstable [DMPO–OOH]˙, which decomposed homolytically to produce ˙OH. These findings revealed a novel ˙OH-generating system mediated by Ru complexes, which were not only dependent on DMPO, but also on ¹O₂ and the presence of H-donating agents. These findings may have broad chemical and biomedical implications.