ISSN:
1573-4951
Keywords:
CoMFA
;
cyclodextrin complexes
;
lipophilicity
;
molecular connectivity
;
molecular recognition
;
multivariate analysis
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract The application of classical QSAR and molecular modeling analysis using Comparative Molecular Field Analysis (CoMFA) to the complexation of some natural and modified cyclodextrins (CDs) with guest molecules was examined. For 1:1 complexation systems between natural β-CD, modified α-, β-, and γ-CD that bear one p-(dimethylamino)benzoyl (DMAB) moiety (DMAB-α-, β-, and γ-CDs) and guest molecules of widely varying chemical structures and properties, the binding constants of the complexes were successfully fitted using multiple linear regression (MLR) with hydrophobic descriptor log P (the partition coefficient between 1-octanol and water phases) and molecular connectivity indices. A non-linear dependency of binding constants on the zero-th and/or first order molecular connectivity index as a measure of size becomes apparent. The modeling performance of the CoMFA models with steric/electrostatic fields to DMAB-α- and β-CD systems was comparable to those of MLR models. However, statistically significant CoMFA models for γ-CD systems which have higher conformational flexibility of the ring could not be obtained. The CoMFA models obtained for DMAB-α- and β-CD systems showed that the predominant effects were steric for the DMAB-α-CD system and electrostatic for the DMAB-β-CD system, respectively.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1008103122313
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