Quantitative structure-stability relationships among inclusion complexes of cyclodextrins. I: Barbituric acid derivatives.
Quantitative structure-stability relationships (QSSRs) are formulated for the inclusion complexation of 17 barbituric acid derivatives with alpha- and beta-cyclodextrin. The variation in the complex stability constants K alpha and K beta 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 alpha also depends upon whether or not R1 is branching or cyclic, and K beta also depends upon whether the guest molecule is a barbiturate or a thiobarbiturate. The results suggest that in alpha-cyclodextrin-barbiturate complexes the cyclodextrin cavity includes only R1, while in beta-cyclodextrin complexes both R1 and (part of) the barbiturate ring are included. This complexation model is compared with those proposed by other authors.
D001463:Barbiturates / Q000032:analysis*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003505:Cyclodextrins / Q000032:analysis*; D003912:Dextrins / Q000032:analysis*; D004355:Drug Stability; D007700:Kinetics; D012995:Solubility; D013213:Starch / Q000032:analysis*; D013329:Structure-Activity Relationship; D013858:Thiobarbiturates / Q000032:analysis; D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins
D001463:Barbiturates; D003505:Cyclodextrins; D003912:Dextrins; D013858:Thiobarbiturates; D047391:alpha-Cyclodextrins; D047392:beta-Cyclodextrins; D013213:Starch; C031215:betadex; C029684:thiobarbituric acid; C032613:alpha-cyclodextrin