Calorimetric Measurements of the Complexation of Cyclosporin A, Ascomycin, Fujimycin, and Rapamycin with Lithium Chloride and with an Immunophilin

Abstract

Abstract Solutions (2 ml) of small linear and cyclic peptides ( 4–11 ), of a peptolide containing nine amino acids and a lactate moiety ( 12 ), of the cyclic undecapeptide cyclosporin A (CS, 1 ), and of the macrolides ascomycin, fujimycin, and rapamycin ( 13–15 ) in THF were added to excess LiCl, LiBr, or LiClO 4 (up to 3000 equiv. in 40 ml THF) in a calorimeter (calorimetric titration). The enthalpies of interaction measured are in the range of Δ H = −8 to −37 kcal/mol. A similar experiment was carried out with one of the binding proteins of cyclosporin, the human cyclophilin A, to give the thermodynamic parameters for the complexation Δ H = −16, Δ G° = −10 kcal/mol, and Δ S° = −20 cal/mol·deg. at 25° which corresponds to an equilibrium 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 shifts of signals of the H‐atoms next to CO and C–OH groups in these molecules.