A DFT/PCM Study on the Affinity of Salinomycin to Bind Monovalent Metal Cations

The affinity of the polyether ionophore salinomycin to bind IA/IB metal ions was accessed using the Gibbs free energy of the competition reaction between SalNa (taken as a reference) and its rival ions: [M(+)-solution] + [SalNa] → [SalM] + [Na(+)-solution] (M = Li, K, Rb, Cs, Cu, Ag, Au). The DFT/PCM computations revealed that the ionic radius, charge density and accepting ability of the competing metal cations, as well as the dielectric properties of the solvent, have an influence upon the selectivity of salinomycin. The optimized structures of the monovalent metal complexes demonstrate the flexibility of the ionophore, allowing the coordination of one or two water ligands in SalM-W(1) and SalM-W(2), respectively. The metal cations are responsible for the inner coordination sphere geometry, with coordination numbers spread between 2 (Au(+)), 4 (Li(+) and Cu(+)), 5/6 (Na(+), K(+), Ag(+)), 6/7 (Rb(+)) and 7/8 (Cs(+)). The metals’ affinity to salinomycin in low-polarity media follows the order of Li(+) > Cu(+) > Na(+) > K(+) > Au(+) > Ag(+) > Rb(+) > Cs(+), whereas some derangement takes place in high-dielectric environment: Li(+) ≥ Na(+) > K(+) > Cu(+) > Au(+) > Ag(+) > Rb(+) > Cs(+).