Characterization of copper(II) interactions with sinefungin, a nucleoside antibiotic: Combined potentiometric, spectroscopic and DFT studies

Abstract

Interactions between sinefungin and copper(II) ions were investigated. Stoichiometry and stability constants of themetal-free system and two mononuclear complexes present in solution were determined on the basis of potentiometricdata analysis. The results were compared to the Cu(II)-ornithine system due to structural similarities between bothmolecules. Combined spectroscopic and theoretical studies allowed for determination of coordination pattern forthe Cu(II)-sinefungin complexes. At acidic pH, copper is bound in "glycine-like" coordination mode, identical with thatof ornithine. This involves α-amino group and the carboxyl oxygen. At higher pH, a "bis-complex" is formed by twosinefungin molecules. The second ligand binds in equatorial position displacing two water molecules, what resultsin the stable 2N,2O coordination. Both axial positions are supposed to be occupied by N1 nitrogen donors of adeninemoiety, what is confirmed by DFT calculations. They interact indirectly with copper(II) through water molecules as theresult of dominant syn conformation of purine.