Ion pairing between Cl- or ClO4- and alkali metal complexes of ionophore antibiotics in organic solvents: A multinuclear NMR and FT-IR study

The extent of ion pairing in chloride and perchlorate salts was studied by measurement of the Cl- and ClO4- resonances and the observation of the perc hlorate stretching frequency by use of nuclear magnetic resonance (NMR) spe ctroscopy and Fourier transform infrared spectroscopy (FT-IR), respectively , for a variety of ionophores in various solutions and in large unilaminar vesicles (LUVs). The NMR line widths of chloride and perchlorate were large r in solutions containing the neutral ionophores valinomycin (Val) and nana ctin (Non) than in solutions containing the negatively charged ionophores n igericin (Nig), lasalocid (Las), and monensin (Mon). The viscosity-correcte d perchlorate NMR line widths in solutions containing Val and Las were sign ificantly negatively correlated (r(2) greater than or equal to 0.99) with t he dielectric constant of the solvent. Solvents with row dielectric constan ts favored ion pair formation. From methanolic solutions containing the Li, Na+, K+, and Cs+ salts of Cl- and ClO4-, it was determined that the catio n with the highest selectivity for the ionophore affords the most ion pairi ng. A decrease in pH from 7 to 3 had no significant effect on the NMR line widths of chloride and perchlorate in methanolic solutions containing Val, whereas a similar decrease in pH in a methanolic solution containing Mon ca used a 2-fold increase in the line widths. The FT-IR difference spectrum of KClO4 in a methanolic solution containing Val showed splitting at the perc hlorate stretching frequency. No band splitting was observed in the FT-IR d ifference spectrum of KClO4 in methanolic solutions containing Las. The ref lux of Cl-35 in LUVs containing the neutral ionophore Val followed first-or der kinetics with an efflux constant of 1.70 x 10(-3) min(-1), as determine d by Cl-35 NMR spectroscopy. The induction of increased membrane permeabili ty in LUVs by the ionophore was determined to be negligible for Val and Nig by fluorescence spectroscopy.