Complexation of several fungicides with beta-cyclodextrin: determination of the association constants and isolation of the solid complexes.

The formation of inclusion complexes with beta-cyclodextrin was studied for several popular fungicides of different types: prochloraz, 2-phenylphenol, thiophanate methyl, 8-hydroxyquinoline, and benalaxyl. Phase solubility diagrams showed that in all cases complexation takes place, leading to an important increase of water solubility in prochloraz and benalaxyl. Equilibrium association constants could be determined from the phase solubility data and from NMR titrations in the case of 2-phenylphenol. Because of the low solubility of the complex formed between 8-hydroxyquinoline and beta-cyclodextrin, the corresponding association constant could not be determined. The solid complexes of fungicide-cyclodextrin were prepared and isolated by different methods. The isolation of real complexes and not physical mixtures was confirmed in the cases of prochloraz, 2-phenylphenol, and benalaxyl by differential scanning calorimetry.