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

Cezomycin, a biosynthetic analogue of calcimycin (A 23187), was studie d to evaluate the effect of changes in structural features on the coor dination and transport of calcium and magnesium. Its protonation and c alcium and magnesium complexation properties were examined at equilibr ium in pure methanol using potentiometric and spectrophotometric metho ds. Like calcimycin, cezomycin forms two complexes with calcium and ma gnesium, 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 m agnitude 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 a mine substituent on the benzoxazole moiety of the calcimycin analogue. Very similar thermodynamic and kinetic behaviours are observed for ce zomycin and X 14885A, two calcimycin analogues with respectively no su bstituent and a hydroxyl group adjacent to the carboxyl function. As w ith calcimycin and X 14855A, a cooperative effect was observed at equi librium 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 c harged AM(+) complexes.