A large number of traditional drugs and the development of new drugs often encounter the problem of poor water solubility. Cucurbit[7]uril, a novel macrocyclic host, has attracted great interest in this field. Investigating the solubilizing effect of drugs by inclusion with cucurbit[7]uril could provide guidance for drug solubilization. In this work, the interactions of drugs with cucurbit[7]uril, drugs with water and the inclusion complexes with water, and the properties of drugs and inclusion complexes, are considered to establish a linear solvation energy relationships (LSER)-based model. This model could be applied to predicting the solubility of drugs with cucurbit[7]uril in water. Density functional theory (DFT) is employed to obtain the properties and interaction parameters. The multi-parameter solubility model obtained by stepwise regression shows good fitting and predicting results. And the surface area of inclusion complexes (A 3), the LUMO energy of inclusion complexes (E 3LUMO), the polarity index of inclusion complexes (I 3), the electronegativity of drugs (χ 1), and the oil-water partition coefficient of drugs (log p 1w) are effective parameters related to the solubilization of drugs with cucurbit[7]uril. Futhermore, the model could be extended to calculate the solubilizing effect of other macrocycles.
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