Photoactivatable Ru complexes containing a Ru[sbnd]O bond: Photoinduced ligand dissociation and DNA damage

Abstract

Ru complexes bearing photolabile ligands exhibit DNA covalent binding capability upon ligand photodissociation and thus show promising application potential as a new type of anticancer agents. Our recent work has shown that [Ru(bpy)2(py-SO3)]+ (complex 1, bpy=2,2′-bipyridine, py-SO3=pyridine-2-sulfonate) can generate py-SO3 radicals along with the photodissociation of py-SO3, leading to DNA covalent binding with Ru fragments and DNA single strand cleavage by py-SO3 radicals simultaneously. In this work, three new Ru complexes, [Ru(bpy)2(qn-SO3)]+ (2), [Ru(bpy)2(py-CO2)]+ (3), and [Ru(bpy)2(qn-CO2)]+ (4) (qn-SO3=quinoline-8-sulfonate, py-CO2=pyridine-2-carboxylate, qn-CO2=quinoline-8-carboxylate) were synthesized and their ligand photodissociation and DNA photodamage properties were compared in depth with that of 1. It was found that 2 undergoes ligand photodissociation more efficiently than 1 and can also generate radicals upon UV irradiation. However, 2 can lead to DNA photodamage via covalent binding only. In sharp contrast, the ligand photodissociation efficiency of 4 is much lower than 1 and 2 and no radicals were found during ligand dissociation, and complex 3 is very stable under the same irradiation conditions. The underlying mechanisms accounting for such a significant disparity between 1-4 were discussed, which may provide guidelines for developing new Ru-based DNA photodamage agents.