Peculiar reactivity of a di-imine copper(II) complex regarding its binding to albumin protein

Author(s)

Silveira, Vivian C. ^[1] ; Abbott, Mariana P. ^[1] ; Cavicchioli, Mauricio ^[1] ; Goncalves, Marcos B. ^[2] ; Petrilli, Helena M. ^[2] ; de Rezende, Leandro ^[1] ; Amaral, Antonia T. ^[1] ; Fonseca, David E. P. ^[3] ; Caramori, Giovanni F. ^[3] ; da Costa Ferreira, Ana M. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Quim, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Fis, Sao Paulo - Brazil

^[3] Univ Fed Santa Catarina, Dept Quim, Florianopolis, SC - Brazil

• Document type: Journal article
• Source: DALTON TRANSACTIONS; v. 42, n. 18, p. 6386-6396, 2013.
• Web of Science Citations: 13

Abstract

A set of four di-imine copper(II) complexes containing pyridine, pyrazine and/or imidazole moieties, {[}Cu-(apyhist) H2O](2+) 1 (apyhist = 2-(1H-imidazol-4-yl)-N-(1-(pyridin-2-yl) ethylidene) ethanamine), {[}Cu(apzhist)-OH](+) 2 (apzhist = 2-(1H-imidazol-4-yl)-N-(1-(pyrazin-2-yl) ethylidene) ethanamine), {[}Cu(apyepy) OH](+) 3 (apyepy = 2-(pyridin-2-yl)-N-(1-(pyridin-2-yl) ethylidene) ethanamine), and {[}Cu(apzepy) H2O](2+) 4 (apzepy = N-(1-(pyrazin-2-yl) ethylidene)-2-(pyridin-2-yl) ethanamine), were investigated regarding their capability of interacting with serum albumin (human, HSA and bovine, BSA), by using spectroscopic techniques, CD, UV/Vis and EPR. Like other similar di-imine copper(II) complexes, most of them showed an expected preferential insertion of the metal ion at the primary N-terminal site of the protein, very selective for copper and characterized by a CD band at 560 nm. Further insertion of the copper ion at a secondary site is expected when using an excess of the metal. However, one of these studied complexes, {[}Cu(apyhist)H2O](2+) 1, exhibited anomalous behaviour interacting only at this secondary metal binding site of albumin, characterized by a CD band at 370 nm, and attributed to the coordination of copper at the Cys34 pocket. Analogous experiments with HSA previously treated with N-ethyl-maleimide (NEM), that oxidizes the protein Cys34 residue and obstructs the metal coordination, verified these results. Additional data obtained by EPR spectroscopy complemented those results. DFT calculations, considering some structural and electronic characteristics of such series of di-imine ligands and of the corresponding copper complexes, suggested molecular recognition of the apyhist ligand at the protein cavity as a feasible explanation for this unexpected and peculiar behaviour of complex 1. (AU)

• FAPESP's process: 11/50318-1 - Development of compounds with pharmacological or medicinal interest and of systems for their transport, detection and recognition in biological media
• Grantee: Ana Maria da Costa Ferreira
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 05/60596-8 - Complex species with potential for application in bio-organics, catalysis, pharmacology and environmental chemistry: conception, preparation, characterization and reactivity
• Grantee: Ana Maria da Costa Ferreira
• Support Opportunities: Research Projects - Thematic Grants