CALORIMETRIC MEASUREMENTS OF THE COMPLEXATION OF CYCLOSPORINE-A, ASCOMYCIN, FUJIMYCIN, AND RAPAMYCIN WITH LITHIUM-CHLORIDE AND WITH AN IMMUNOPHILIN

Solutions (2 ml) of small linear and cyclic peptides (4-11), of a pept olide containing nine amino acids and a lactate moiety (12), of the cy clic undecapeptide cyclosporin A (CS, 1), and of the macrolides ascomy cin, fujimycin, and rapamycin (13-15) in THF were added to excess LiCl , LiBr, or LiClO4 (up to 3000 equiv. in 40 ml THF) in a calorimeter (c alorimetric titration). The enthalpies of interaction measured are in the range of Delta H = -8 to -37 kcal/mol. A similar experiment was ca rried out with one of the binding proteins of cyclosporin, the human c yclophilin A, to give the thermodynamic parameters for the complexatio n Delta H degrees = -16, Delta G degrees = -10 kcal/mol, and Delta S d egrees = -20 cal/mol.deg. at 25 degrees which corresponds to an equili brium constant K = 2.10(7) l/mol, in good agreement with the result of independent measurements using different methods. NMR Measurements of the macrolides in (D-8)THF containing LiCl show strong down-field shi fts of signals of the H-atoms next to C=O and C-OH groups in these mol ecules.