X-14885A: An ionophore closely related to calcimycin (A-23187). NMR, thermodynamic, and kinetic studies of cation selectivity
Résumé
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 A 2Mg 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 +) and 2:1 (A 2M) stoichiometries, following the sequence Ca 2+ > Mg 2+ > Sr 2+ > Ba 2+. For AM + + A - ⇄ A 2M, 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 A 2Mg and A 2Ca 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 +, 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 the 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.