Two ruthenium(II) complexes, trans-[Ru(sac)2(dpq)2] (1) and trans-[Ru(sac)2(dppz)2] (2), where sac is artificial sweetener saccharin (o-sulfobenzimide; 1,2-benzothiazole-3(2H)-one1,1-dioxide (Hsac)), dpq = dipyrido[3,2-d:2’,3’-f]quinoxaline and dppz = dipyrido[3,2-a:2′,3′-c]phenazine have been synthesized and thoroughly characterized using various analytical and spectral techniques. Saccharin is known to act as carbonic anhydrase IX (CA IX) inhibitor, which is a biomarker and implicated in highly aggressive and proliferative tumors in hypoxic stress. Many aggressive tumors having a hypoxic core, therefore inhibition of CA IX is a potential strategy for anticancer chemotherapy. The solid-state structures, photophysical properties, photostability, DNA and protein binding affinity, and DNA photocleavage activity of complexes 1 and 2 were explored. The photo-induced dissociation of the monodentate saccharinate is observed when irradiated at UV-A light of 365 nm. The complexes show significant binding affinity to the calf thymus (CT)-DNA (Kb ~ 105 M−1) through significant intercalation through planar dpq and dppz ligands. Interaction of complexes 1 and 2 with bovine serum albumin (BSA) showed remarkable tryptophan emission quenching (KBSA ~105 M−1). The complexes showed appreciable photoinduced DNA cleavage activity upon irradiation of low power UV-A light of 365 nm from supercoiled (SC) to its nicked circular (NC) form at micromolar complex concentrations. Photocleavage mechanistic studies reveal the involvement of reactive oxygen species (ROS) mediated through ligand-centered 3pp* and/ or 3MLCT excited states generated upon photoactivation leads to nicking of supercoiled (SC) DNA to nicked circular (NC)form. In the absence of O2, we also observed photocleavage of DNA through the formation of photoinduced ligand dissociated Ru-DNA complex suggesting a possible photoactivated chemotherapeutic (PACT) pathway.

Ruthenium(II) complexes of saccharin with dipyridoquinoxaline and dipyridophenazine: Structures, biological interactions and photoinduced DNA damage activity

ACS Spring 2022

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