Development of QSAR model for predicting the inclusion constants of organic chemicals with α-cyclodextrin
- 9 Downloads
Solubility is a crucial limiting factor in pharmaceutical research and contaminated site remediation. Cyclodextrin, with its structure of hydrophilic exterior and hydrophobic cavity, has a potential ability to enhance the hydrophobic chemical’s solubility through the formation of host–guest complex. The stability of host–guest complex is often quantified by the inclusion constant. In this study, the logarithm of 1:1 α-cyclodextrin inclusion constants (log K α ) for 195 organic chemicals was collected. With this parameter as the endpoint, a quantitative structure–activity relationship (QSAR) model was developed using DRAGON descriptors and stepwise multiple linear regression analysis. The model statistics parameters indicated that the established model had a good determination coefficient of 0.857, a high cross-validation coefficient of 0.835, a low root mean square error of 0.380, together with the acceptable results of external validation, which indicate a satisfactory goodness-of-fit, robustness, and predictive ability of the model. Based on the screened eight descriptors, we propose an appropriate mechanism interpretation for the inclusion interaction. Additionally, the applicability domain of the current model was characterized by the Euclidean distance-based method and Williams plot, and results indicated that the model covered a large number of structurally diverse chemicals belonging to 13 different classes. Comparing with the previous reported models, this model has obvious advantages with a larger dataset, a higher value of correlation coefficient, and a wider application domain.
KeywordsQuantitative structure–activity relationship model Inclusion constant Cyclodextrin Organic chemicals
The study was supported by the National Natural Science Foundation of China (No. 21507061, No. 21507038, and No. 41671489) and the Natural Science Foundation of Jiangsu Province (No. BK20150771).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
The transparency document associated with this article can be found in the online version.
- Mocelo-Castell R, Villanueva-Novelo C, Cáceres-Castillo D, Carballo RM, Quijano-Quiñones RF, Quesadas-Rojas M, Cantillo-Ciau Z, Cedillo-Rivera R, Moo-Puc RE, Moujir LM, Mena-Rejón GJ (2015) 2-Amino-4-arylthiazole derivatives as anti-giardial agents: synthesis, biological evaluation and QSAR studies. Open Chem 13:1127–1136CrossRefGoogle Scholar
- Mousset E, Oturan N, van Hullebusch ED, Guibaud G, Esposito G, Oturan MA (2014) Influence of solubilizing agents (cyclodextrin or surfactant) on phenanthrene degradation by electro-Fenton process—study of soil washing recycling possibilities and environmental impact. Water Res 48:306–316CrossRefGoogle Scholar
- OECD (2007) Guidance document on the validation of (quantitative) structure–activity relationships [(Q)SAR] models. Organisation for Economic Co-Operation and Development, Paris, France. <http://www.oecd.org/env/ehs/risk-assessment/guidancedocumentsandreportsrelatedtoqsars.htm>
- Shariati-Rad M, Hasani M (2013) Linear and nonlinear quantitative structure–property relationships modeling of charge–transfer complex formation of organic donors with iodine and iodine monochloride using partial least squares and radial basis function–partial least squares. J Iran Chem Soc 10:1247–1256CrossRefGoogle Scholar