Fine-tuning the Photochemistry of Sulfur-Based Linkages with Ruthenium(II) Polypyridyl Complexes for Optimal PACT Application.

Abstract

The thioether-based monodentate ligands are reported to be efficient photoreleasable groups from Ru(II)-photocages designed for photoactivated chemotherapy (PACT). However, the direct comparison and systematic studies of the photochemical behavior of sulfur linkages of varied electronic/oxidation states, i.e., sulfoxides, thioethers, or thiols coordinated with Ru(II)-polypyridyls, remain unexplored. To delve into the intricate photochemistry of Ru(II)-S linkages, two Ru(II)-polypyridyls: [Ru(ttpy)(phen)(DMSO)](PF₆)₂ [1](PF₆)₂ and [Ru(ttpy)(phen)(DAS)](PF₆)₂ [2](PF₆)₂, [ttpy = 4'-tolyl-2,2':6',2″-terpyridine, phen = 1,10-phenanthroline, DAS = diallyl sulfide, DMSO = dimethyl sulfoxide] were synthesized. Here, we used DMSO for the typical sulfoxide linkage, while DAS a biologically potent phytochemical, probed as a thioether linkage with Ru(II). The photosolvolysis monitored by UV/Vis and ¹H NMR studies with white LED in CH₃CN indicated more facile substitution of DAS than that of DMSO. The water-soluble [1](NO₃)₂ and [2](NO₃)₂ exhibited facile photorelease of DAS than DMSO from {Ru(ttpy)(phen)}²⁺-photocages in water. The cytotoxicity and photocytotoxicity studies with HeLa and Caco2 cells showed that [2](PF₆)₂ and [2](NO₃)₂ were more photocytotoxic with higher photoindices (PI) compared to [1](PF₆)₂ and [1](NO₃)₂. This apparently led to the conclusion that markedly facile photorelease of DAS resulted in higher photocytotoxicity of the DAS-based complexes. Therefore, thioether-based Ru(II)-polypyridyls portray better options for photocaging of prodrugs and PACT applications.