Free acid, anion, alkali, and alkaline earth complexes of lasalocid a (X537A) in methanol: structural and kinetic studies at the monomer level.

Abstract

We report below on nuclear magnetic resonance investigations of the structure and exchange kinetics for the free acid, anion, sodium complex, and barium complex of the ionophore lasalocid A (X537A) in methanol solution. A comparison between the proton and carbon longitudinal relaxation times of lasalocid in nonpolar and polar solvents demonstrates that the free acid (HX) is a monomer in methanol solution. Parallel proton and carbon relaxation measurements demonstrate that the anion (X-), sodium complex (NaX), and barium complex (BaX+) are also monomeric in methanol solution. These results are in contrast to the Na2X2 dimer and the BaX2-H20 dimer observed in crystals and in nonpolar (cyclohexane and methylene chloride) solutions. Large downfield shifts on complex formation (X- to NaX and BaX+) are detected for protons located on the polar face of the ionophore with their C-H bonds directed towards and proximal to the metal ion. The exchange of lasalocid anion between free (X-) and complexed (BaX+) states in methanol can be monitored from the temperature-dependent line shapes of the proton resonances at superconducting fields. The exchange rates are independent of the reactant concentrations and are characteristic of a rate-determining dissociation of BaX+ in methanol solution with activation parameters delta H++ = 6.5 kcal mol-1 (25 degrees) and delta S++ = -20.0 cal mol-1 degree -1 (1 cal = 4.184 J). The rate constants for dissociation and formation of BaX+ complex in methanol, 25 degrees, are 5.2 X 10(3) sec-1 and 1.5 X 10(10) M-1 sec-1, respectively. These studies were extended to derive the activation parameters for the exchange of lasalocid anion between BaX+ and NaX and between BaX+ and HX in methanol, while the exchange among HX, X-, and NaX is too rapid to be monitored on the time scale of nuclear magnetic resonance.