Binding affinity studies of 1,2,3-triazole copper(II) complexes to human serum albumin

Autor(es)

de Paula, Queite A. ; Joly, Jean-Pierre ; Selmeczi, Katalin ; Fonseca, David E. P. ; Caramori, Giovanni F. ; Farrell, Nicholas P. ; Da Costa Ferreira, Ana M.

• Tipo de documento: Artigo Científico
• Fonte: Journal of Coordination Chemistry; v. 71, n. 11-13, p. 16-pg., 2018-01-01.

Resumo

Two copper(II) complexes with tetradentate 1,4-disubstituted-1,2,3-triazole ligands, [CuL(MeCN)](ClO4)(2) (1) and [CuL](ClO4)(2) (2), have been prepared and characterized by different techniques, including X-ray structure determination, spectroscopic, and electrochemical measurements, as reported elsewhere. Herein, we report the interactions of these complexes, and corresponding free ligands, with human serum albumin (HSA) verifying their relative thermodynamic stability and differences in binding to this protein. Interactions with HSA were verified by CD measurements monitored at 564nm, up to stoichiometric ratio 2:1 [Complex]:[protein], according to competitive equilibria involving the insertion of copper at the selective N-terminal metal binding site in HSA, and additionally at a secondary nonselective site. Further interactions of these complexes with L-tryptophan residues, and probable supplementary site(s) for the binding, were followed by fluorescence measurements. Analogous experiments with the free L and L indicated much weaker interactions. Protein oxidation damage was observed for both complexes, monitored by carbonyl groups formation in the presence of H2O2, probably with the participation of reactive oxygen species. Density functional theory calculations exhibit metal-ligand binding interaction energies similar to [Cu(HSA-N-terminal)](+), and reinforced the experimental results, showing clearly that such triazole ligands are competitive toward copper(II) in biological medium. [GRAPHICS] . (AU)

• Processo FAPESP: 11/50204-6 - Especies complexas de cobre e zinco com ligantes triazolicos: sintese, caracterizacao e estudo de atividade biologica.
• Beneficiário: Queite Antonia de Paula
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/07937-8 - Redoxoma
• Beneficiário: Ohara Augusto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 11/50318-1 - Desenvolvimento de compostos com interesse farmacológico ou medicinal e de sistemas para seu transporte, detecção e reconhecimento no meio biológico
• Beneficiário: Ana Maria da Costa Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Temático