Structural, protonation, and complexation studies of ionophores A23187, 4-ClA23187, and 23,24-Br(2)A23187.

Abstract

A23187 is a carboxylic acid polyether ionophore best known for transporting calcium through membranes. However, it has been shown that it transports Zn 2+, Cd2+, and Mn2+ more selectively than Ca2+. Derivatives of A23187 may increase this selectivity by disrupting the hydrogen bonding network of MA2 complexes and selectively transporting metal ions by alternate transport complexes. The goal of this project is to characterize binding properties of two derivatives, 4-ClA23187 and 23,24-Br2A23187, which may exhibit an increase in selectivity (relative to A23187) for metal ions Zn2+, relative to Ca2+.

Protonation properties have been studied for A23187, and one new protonation constant, pKa2 (representing the deprotonation of the pyrrole nitrogen), was measured to be 11.4. 4-ClA23187 and 23,24-Br2A23187 also were found to have pKa2 values of 11.4.

The derivative 23,24-Br2A23187 was determined to have approximately equal KHMA values as the parent compound, and increased selectivity for transport of Zn2+, Cd2+, and Mn2+ over Ca2+. The basis for the increase in selectivity may be due to the higher values for KMA for Zn2+ and Cd2+ than for Ca2+. The MA complex has four donor atoms from one ligand and a neutral charge, which may be sufficient to transport some divalent metal ions with no additional ions binding to the complex.

The derivative 4-ClA23187 was determined to have lower binding constants for KHMA than the parent compound, and increased transport selectivity of Zn2+, Cd2+, and Mn2+ over Ca2+. The basis for this increase in selectivity may be due to the lower binding constants (KHMA and KMA2) than the parent compound, and a weakened hydrogen bond network due to the presence of the chlorine substituent on the benzoxazole moiety.