1H and 13C NMR study of the complex formed by copper(II) with the nucleoside antibiotic sinefungin

Sinefungin (SFG) is an antifungal and antiparasitic nucleoside antibiotic composed by ornithine and adenosine moieties both having the potential to bind copper(II). NMR studies performed at physiological pH have shown that the α-amino and the carboxylate groups in the ornithine unit are the preferred donor sites for Cu(II) binding. On the contrary, at acidic pH, Cu(II) complexation starts from adenosine nitrogen being the α-amino group still protonated and not available for metal binding. The proton paramagnetic relaxation enhancements measured at neutral pH allowed to obtain the 3D structure of the 1:2 Cu(II)–SFG complex. Molecular dynamics calculations were revealing for the existence of secondary Cu(II) interaction with the purine nitrogens of the adenosine moiety.