Copper(II), a Peculiar Metal Ion for Complexation With Monensin A Ionophore

Monensin A transports Na⁺ ions through the cell membrane, but it is also able to bind divalent metal ions potentially influencing the biological activity of the ionophore. In line with our previous studies, here we explored interaction of the essential Cu(II) with monensinate A and suggested the types of coordination compounds formed. Circular dichroism (VIS- and NIR-CD), VIS light absorption, and electron paramagnetic resonance (EPR) spectroscopies, as well as electrospray ionization mass spectrometry (ESI-MS) were utilized for identification and characterization of the complexes. Bis or mono Cu(II) complexes prevailed at ligand excess or comparable reactant concentrations, respectively. Excess Cu(II) salt, however, induced the formation of dinuclear coordination species, not observed previously with divalent metal cations as Mg(II), Ca(II), Co(II), Mn(II), Ni(II), Zn(II). The dinuclear complex is EPR-active being a rare example of non-EPR-silent coordination compounds containing two Cu(II) centers and is the first case among the known metal(II) complexes of the antibiotic monensin A. The origin of the counterion did not influence the properties of the bis compound but contributed to the spectral behavior of the newly detected dinuclear Cu(II) species. This study revealed that the interactions of a drug molecule with metal(II) ions during its practical application may be significant and it should be considered in discussions about the mechanism of action.