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

Autor(es)

Neves da Silva, Camila Fontes ^[1] ; Possato, Bruna ^[1] ; Franco, Lilian Pereira ^[1] ; Barbosa Ramos, Loyanne Carla ^[2] ; Nikolaou, Sofia ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, Av Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Av Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Inorganic Biochemistry; v. 186, p. 197-205, SEP 2018.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 14/25561-8 - Carboxilatos trinucleares de rutênio com ligantes funcionais CO, NO e intercaladores: estudo químico e de interações com biomoléculas alvo
• Beneficiário: Camila Fontes Neves da Silva
• Linha de fomento: Bolsas no Brasil - Doutorado
• Processo FAPESP: 15/20302-7 - Uso de anti-inflamatórios não esteroidais, azanaftalenos e fenazinas como ligantes na obtenção de carboxilatos bi- e trinucleares de rutênio com potencial atividade antialérgica, tumoricida e tripanocida
• Beneficiário: Sofia Nikolaou
• Linha de fomento: Auxílio à Pesquisa - Regular