Biogenic amine-ionophore interactions: Structure and dynamics of lasalocid (X537A) complexes with phenethylamines and catecholamines in nonpolar solution

Abstract

The ionophore lasalocid A forms 1:1 complexes with phenethylamines (1-amino-1-phenylethane and 1-amino-2-phenylethane) and catecholamines (dopamine and norepinephrine) in nonpolar solution. We have undertaken high-resolution proton nuclear magnetic resonance studies to deduce structural and kinetic information on the ionophore-biogenic amine complexes in chloroform solution. The coupling constant, chemical shift, and relaxation time data demonstrate that the lasalocid backbone conformation and the primary amine binding sites in the complexes are similar to those determined earlier for the alkali and alkaline earth complexes of this ionophore in solution. The exchange of lasalocid between the free acid (HX) and the primary amine complexes (RNH(3)X) in chloroform solution have been evaluated from the temperature-dependent line shapes at superconducting fields. The kinetic parameters associated with the unimolecular dissociation [Formula: see text] and the bimolecular exchange [Formula: see text] reactions have been deduced from an analysis of the lifetime of the complex as a function of the reactant concentrations. The relative stability of the complex decreases in the order phenyl > n-pentyl for substituents on the carbon alpha to the amino group (1-amino-1-phenylethane and 2-aminoheptane) and phenyl > 3,4-dihydroxyphenyl for substituents on the carbon beta to the amino group (1-amino-2-phenylethane and dopamine). These results suggest that nonpolar interactions between the biogenic amine side chain and the lasalocid molecule contribute to the stability of the complex in solution.