CLOSELY-RELATED IONOPHORES CEZOMYCIN AND CALCIMYCIN (A-23187) - COOPERATIVE FORMATION OF THE TRANSPORTING SPECIES

Cezomycin, a biosynthetic analogue of calcimycin (A 23187), was studied to evaluate the effect of changes in structural features on the coordination and transport of calcium and magnesium. Its protonation and calcium and magnesium complexation properties were examined at equilibrium in pure methanol using potentiometric and spectrophotometric methods. Like calcimycin, cezomycin forms two complexes with calcium and magnesium, a neutral two-Iigand A(2)M complex and a charged species AM(+). The calcium species are slightly more stable than the corresponding magnesium species, and the cezomycin complexes are about 1 order of magnitude less stable than the corresponding calcimycin complexes. The dissociation kinetics of the complexes under acidic conditions showed no protonated kinetic intermediate complex, there being no secondary amine substituent on the benzoxazole moiety of the calcimycin analogue. Very similar thermodynamic and kinetic behaviours are observed for cezomycin and X 14885A, two calcimycin analogues with respectively no substituent and a hydroxyl group adjacent to the carboxyl function. As with calcimycin and X 14855A, a cooperative effect was observed at equilibrium for the formation of the neutral A(2)M complexes and confirmed by the formation and dissociation mechanisms, postulated from kinetic investigations, which show that the rate-limiting steps involve the charged AM(+) complexes.