Thermodynamic and MD studies of anion complexation by cyclopentaleucine in acetonitrile and dimethyl sulfoxide

Complexation affinity of cyclic pentaleucine for halogen anions, thiocyanate and oxoanions was studied in acetonitrile and dimethyl sulfoxide. Equilibrium constants and derived Gibbs energies, as well as enthalpies and entropies of the corresponding reactions were determined by means of microcalorimetric and H-1 NMR titrations. To get more detailed insight into the binding of anions by the cyclopeptide, classical molecular dynamics simulations were carried out. The preorganization of cyclopentaleucine binding site by inclusion of solvent molecules was observed in acetonitrile by these simulations. The investigated receptor showed larger affinity for all anions in acetonitrile than in dimethyl sulfoxide. The results of H-1 NMR studies and those of molecular dynamics simulations indicated that the bound anions were coordinated by the amide groups of cyclopeptide. The stoichiometry of most of the complexes was 1:1 (receptor:anion), with the exception of dihydrogen phosphate and hydrogen sulfate complexes, where higher stoichiometries (1:2 and 2:1, respectively) were also observed. In the case of complexes with H2PO4- anion, in both acetonitrile and dimethyl sulfoxide the binding of dihydrogen phosphate dimer was observed, whereas the species in which two ligands coordinate one HSO4- ion was observed in acetonitrile. The obtained thermodynamic reaction parameters and the observed rather strong solvent effect on the studied equilibria were discussed regarding anions and receptor structural properties as well as solvation abilities of the solvents used.