SOLVENT-DEPENDENT CONFORMATION AND HYDROGEN-BONDING CAPACITY OF CYCLOSPORINE-A - EVIDENCE FROM PARTITION-COEFFICIENTS AND MOLECULAR-DYNAMICS SIMULATIONS

The partition coefficient of cyclosprin A (CsA) was measured in octano l/water and heptane/water by centrifugal partition chromatography. By comparison with results from model compounds, it was deduced that the hydrogen-bonding capacity of CsA changed dramatically from an apolar s olvent (where it is internally H-bonded) to polar solvents (where it e xposes its H-bonding groups to the solvent). Molecular dynamics simula tions in water and CCl4 support the suggestion that CsA undergoes a so lvent-dependent conformational changes and that the interconversion pr ocess is slow on the molecular dynamics time scale.