Substitution behavior of square-planar and square-pyramidal Cu(II) complexes with bio-relevant nucleophiles

Abstract

Substitution reactions of [CuCl₂(en)] and [CuCl₂(terpy)] complexes (where en = 1,2-diaminoethane and terpy = 2,2′:6′,2″-terpyridine) with bio-relevant nucleophiles such as inosine-5′-monophosphate (5′-IMP), guanosine-5′-monophosphate (5′-GMP), L-methionine (L-Met), glutathione (GSH) and DL-aspartic acid (DL-Asp) have been investigated at pH 7.4 in the presence of 0.010 M NaCl. Mechanism of substitution was probed via mole-ratio, kinetic, mass spectroscopic and EPR studies at pH 7.4. In the presence of an excess of chloride, the octahedral complex anion [CuCl₄(en)]²⁻ is formed rapidly while equilibrium reaction was observed for [CuCl₂(terpy)]. Different order of reactivity of bio-molecules toward Cu(II) complexes was observed. Mass spectrum of [CuCl₂(terpy)] in Hepes buffer has shown two new signals at m/z = 477.150 and m/z = 521.00, assigned to [CuCl(terpy)]⁺-Hepes fragments of coordinated Hepes buffer. These signals also appear in the mass spectra of ligand substitution reactions between [CuCl₂(terpy)] and bio-molecules in molar ratio 1:1 and 1:2. According to EPR data, L-Met forms the most stable complex with [CuCl₂(en)] among the ligands considered, while [CuCl₂(terpy)] complex did not show significant changes in its square-pyramidal geometry in the presence of the buffer or bio-ligands.

Keywords:

• Copper(II)
• bio-molecules
• structure – reactivity correlation
• kinetics
• MS analysis
• EPR studies

Acknowledgements

EPR and mass spectrometry measurements were conducted in Magnetic Resonance Research and Chemical Analysis and Materials Research Centers in the Research Park of Saint-Petersburg State University with the kind help from E.A. Bessonova, D.V. Dzema, and S.M. Sukharzhevskii. The authors also thank Dr K. Kämpf (Laboratory of Biomolecular NMR, St. Petersburg State University) and Prof. M.G. Shelyapina (Faculty of Physics, St. Petersburg State University) for their valuable help. E. Selimović and T. Soldatović gratefully acknowledge financial support from State University of Novi Pazar, Novi Pazar, Republic of Serbia.