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

Two novel triruthenium clusters, {[}Ru-3(mu(3)-O)(mu-OOCCH3)(6)(NO)L-2]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 lambda(irrad) = 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 (lambda(irrad) = 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 (K-SV = 9.49 x 10(7) M-1 at T = 298?K) and suggested that the nature of the interaction between complex 2 and HSA is hydrophobic (Delta H = 80.81 kJ/mol and Delta S = 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. (AU)