Solubility and molecular modeling of triflumizole-β-cyclodextrin inclusion complexes

Solubility enhancement of the fungicide triflumicole by β-cyclodextrin is explained using a thermodynamic approach. The influence of organic cosolvents on the overall equilibrium constants of triflumizole complexation with β-cyclodextrin in aqueous solutions has been investigated. Their variance in mixed solvents is only partly explained by a competitive inclusion of substrate and cosolvent molecules in β-cyclodextrin. The geometries of host-guest complexes have been estimated by molecular mechanics calculations. Their broad structural variety caused by the flexibility of host and guest molecules and different association 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 energy, calculated from the solvent accessible surface area of the complex and the conformational (potential) energy.