X-14885A: An Ionophore Closely Related to Calcimycin (A-23187). NMR, Thermodynamic, and Kinetic Studies of Cation Selectivity

Article abstract of DOI:10.1021/ja00205a007

X-14885A is an open-chain carboxylic ionophore, recently isolated from a Streptomyces strain.NMR data have shown that the free acid form adopts a pseudocyclic conformation in chloroform, while in the neutral A2Mg complex a rotation of the benzoxazole arm is achieved to accommodate the cation in a sandwich system.The replacement of the -NHMe by an -OH function and of a methyl group by H in position 15 for X-14885A does not lead to a large modification in the conformation of the new microbial metabolite in solution.The acid-base equilibria and the thermodynamics of association with alkali and alkali-earth cations are determined in methanol, from potentiometric and spectrophotometric measurements.Divalent cations M(2+) form strong complexes of 1:1 (AM(1+)) and 2:1 (A2M) stoichiometries, following the sequence Ca(2+) > Mg(2+) > Sr(2+) > Ba(2+).For AM(1+) + A(1-) <==> A2M, log K_A2M are, respectively, 8.0, 7.3, 6.9, and 6.2 (I=0).A complete kinetic study is carried out in methanol for the A2Mg and A2Ca complexes, with use of a stopped-flow system.This work shows that the rate-limiting steps of the formation and dissociation mechanisms are associated with the charged complex AM(1+), the addition or loss of the second ligand being faster.As for the closely related ionophore A-23187 (calcimycin), the selectivity calcium/magnesium has predominantly a kinetic origin, with faster formation and dissociation rates of calcium complexes.The replacement of the -NHMe group in calcimycin by an -OH group in X-14885A has a drastic effect in the acid-base properties of X-14885A and on the acid-catalyzed dissociation pathway of its complexes.