QSPR Modelling With the Topological Substructural Molecular Design Approach: beta-Cyclodextrin Complexation

• Type: Article in International Scientific Journal
• Date: 2009

Authors

Alfonso Perez Garrido (Author) Other; Aliuska M Morales Helguera (Author) Other; Natalia N D S Cordeiro (Author) FCUP; Amalio G Garrido Escudero (Author) Other

Journal

Title: Journal of Pharmaceutical Sciences

Vol. 98

Pages: 4557-4576

ISSN: 0022-3549

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 17 Citations

Scopus - 22 Citations

Scientific classification

FOS: Natural sciences > Chemical sciences

Other information

Authenticus ID: P-003-E2A

DOI: 10.1002/jps.21747

Abstract (EN): This study aims at developing a quantitative structure-property relationship (QSPR) model for predicting complexation with beta-cyclodextrins (beta-CD) based on a large variety of organic compounds. Molecular descriptors were computed following the TOPological Substructural MOlecular DEsign (TOPS-MODE) approach and correlated with beta-CD complex stability constants by linear multivariate data analysis. This strategy afforded a final QSPR model that was able to explain around 86% of the variance in the experimental activity, along with showing good internal cross-validation statistics, and also good predictivity on external data. Topological substructural information influencing the complexation with beta-CD was extracted from the QSPR model. This revealed that the major driving forces for complexation are hydrophobicity and van der Waals interactions. Therefore, the presence of hydrophobic groups (hydrocarbon chains, aryl groups, etc.) and voluminous species (Cl, Br, I, etc.) in the molecules renders easy their complexity with beta-CDs. To our knowledge, this is the first time a correlation between TOPS-MODE descriptors and complexing abilities of beta-CDs has been reported. (C) 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci98:4557-4576, 2009

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 20