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

Autor: da Silva CFN; Departamento de Química da Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto - Universidade de São Paulo, Av. Bandeirantes 3900, ZIP-CODE 14040-901 Ribeirão Preto, SP, Brazil., Possato B; Departamento de Química da Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto - Universidade de São Paulo, Av. Bandeirantes 3900, ZIP-CODE 14040-901 Ribeirão Preto, SP, Brazil., Franco LP; Departamento de Química da Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto - Universidade de São Paulo, Av. Bandeirantes 3900, ZIP-CODE 14040-901 Ribeirão Preto, SP, Brazil., Ramos LCB; Faculdade de Ciências Farmacêuticas de Ribeirão Preto - Universidade de São Paulo, Av. Bandeirantes 3900, ZIP-CODE 14040-901 Ribeirão Preto, SP, Brazil., Nikolaou S; Departamento de Química da Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto - Universidade de São Paulo, Av. Bandeirantes 3900, ZIP-CODE 14040-901 Ribeirão Preto, SP, Brazil. Electronic address: sofia@ffclrp.usp.br.
Jazyk: angličtina
Zdroj: Journal of inorganic biochemistry [J Inorg Biochem] 2018 Sep; Vol. 186, pp. 197-205. Date of Electronic Publication: 2018 May 30.
DOI: 10.1016/j.jinorgbio.2018.05.021
Abstrakt: Two novel triruthenium clusters, [Ru 3 (μ 3 -O)(μ-OOCCH 3 ) 6 (NO)L 2 ]PF 6 (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 λ 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 (λ 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 × 10 7  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.
(Copyright © 2018 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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