The role of ancillary ligand substituents in the biological activity of triruthenium-NO complexes

Abstract

Two novel triruthenium clusters, [Ru3(μ3-O)(μ-OOCCH3)6(NO)L2]PF6 (L = 4‑acetylpyridine, 1, or 4‑tert‑butylpyridine, 2) release NO. Their spectroscopic and electrochemical characterization confirmed their structure. These complexes efficiently deliver NO in solution under irradiation at λirrad = 377 nm and/or through chemical reduction with ascorbic acid. Clusters 1 and 2 elicit vasodilation and, at concentrations of 10−5 M, can relax up to 100% of pre-contracted rat aorta. Complex 2 is more cytotoxic to murine melanoma B16F10 cells than complex 1: at 50 times lower concentration than complex 1, complex 2 decreases cell viability to 50% in the dark or under irradiation with visible light (λirrad = 527 nm). The higher cytotoxicity of complex 2 can be assigned to its larger hydrophobicity, promoted by the methylated tert‑butylpyridine ancillary ligand in its structure. Investigation into human serum albumin (HSA) fluorescence quenching by clusters 1 or 2 revealed that complex 2 quenches HSA luminescence with a very high Stern-Vomer constant (KSV = 9.49 × 107 M−1 at T = 298 K) and suggested that the nature of the interaction between complex 2 and HSA is hydrophobic (ΔH = 80.81 kJ/mol and ΔS = 334.71 J/K mol). HSA lifetime and circular dichroism data pointed to a static quenching mechanism for both complexes. Together, our results show that a hydrophobic substituent in the cluster ancillary ligand improves NO release ability, cytotoxicity, and interaction with a bio-target.