Quantitative structure-stability relationships among inclusion complexes of cyclodextrins I: Barbituric acid derivatives

Article abstract of DOI:10.1002/jps.2600740223

Quantitative structure-stability relationships (QSSRs) are formulated for the inclusion complexation of 17 barbituric acid derivatives with α- and β-cyclodextrin. The variation in the complex stability constants K(α) and K(β) is found to be partly accounted for by the molar refractivity or the hydrophobicity of the substituent R₁ at position 5 of the barbiturate ring. In addition K(α) also depends upon whether or not R₁ is branching or cyclic, and K(β) also depends upon whether the guest molecule is a barbiturate or a thiobarbiturate. The results suggest that in α-cyclodextrin-barbiturate complexes the cyclodextrin cavity includes only R₁, while in β-cyclodextrin complexes both R₁ and (part of) the barbiturate ring are included. This complexation model is compared with those proposed by other authors.