SOLUBILITY AND MOLECULAR MODELING OF TRIFLUMIZOLE-BETA-CYCLODEXTRIN INCLUSION COMPLEXES

Solubility enhancement of the fungicide triflumicole by beta-cyclodext rin is explained using a thermodynamic approach. The influence of orga nic cosolvents on the overall equilibrium constants of triflumizole co mplexation with beta-cyclodextrin in aqueous solutions has been invest igated. Their variance in mixed solvents is only partly explained by a competitive inclusion of substrate and cosolvent molecules in beta-cy clodextrin. The geometries of host-guest complexes have been estimated by molecular mechanics calculations. Their broad structural variety c aused by the flexibility of host and guest molecules and different ass ociation possibilities of triflumizole have been analysed by a dynamic Monte Carlo docking method. The hydrophobic effect has been simulated by cominimization of the hydrophobic contributions to the solvation e nergy, calculated from the solvent accessible surface area of the comp lex and the conformational (potential) energy.