A LSER-based model to predict the solubilizing effect of drugs by inclusion with cucurbit[7]uril. Issue 41 (26th June 2020) - Cheng, Enping
Abstract : A LSER model was built for predicting the solubility of inclusion complexes. Abstract : 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.