Studies of the complexation reactions of polyether ionophore antibiotics nigericin and salinomycin with lead(II), zinc, calcium, magnesium, sodium and potassium cations.

Abstract

CD studies in 80% methanol-water indicate that Pb2+ forms 1:1 complexes almost quantitatively with monensin, nigericin, narasin, maduramicin, and salinomycin. UV-Vis titrations in 80% methanol-water showed the same result for nigericin and salinomycin.

The lead complexes of nigericin and salinomycin were prepared and were subjected to elemental and MS analysis. Equilibrium constants are determined in this work. The protonation constants of salinomycin (log K H 6.49) and nigericin (log KH 7.02) were determined in 80% methanol-water using potentiometric titrations. For a better comparison of the complexation behavior of the ionophores with lead and other metal ions, potentiometric titrations were done in the presence of metal ions. Complex formation constants, KML, were determined in 80% methanol-water for H+, Pb2+, Na+, K+, Ca2+, Mg2+, and Zn2+ by potentiometric titrations. The values of KpbL are 5 x 102 to 104 larger than the corresponding constants, KML, for the other metals tested. These studies also show that a substantial fraction of complexed ionophores exist as the neutral PbL(OH) species at pH 7--8. Information about the binding sites and conformation of ionophore-metal complexes was obtained using NMR. All the information obtained in this work was used to explain the lead transport data from the vesicle studies of ionophores.

Salinomycin and nigericin are members of polyether carboxylic acid ionophores. Recent studies using phospholipid vesicles show that these compounds transport Pb2+ with high selectivity relative to other divalent cations. The purpose of this work is to help explain the high selectivity of these ionophores for lead over other metal ions.