engleski

Binding interactions of indole derivatives with beta cyclodextrin

Indole-3-acetic acid (IAA), the principal natural auxin, is involved in regulation of practically all aspects of plant growth and development. The molecular mechanism of auxin perception and response is complex and is still not fully understood. Cyclodextrins are cyclic oligosaccharides of toroidal shape, with a relatively hydrophobic central cavity and a hydrophilic exterior. They are able to form inclusion complexes with organic compounds of appropriate size and polarity, which make them attractive model systems for studying ligand-receptor interactions. Here we present the relative binding constants to beta-cyclodextrin for IAA and 29 indolic compounds, obtained by high-performance liquid chromatography. In order to get some insight into the recognition mechanism, a QSPR (quantitative structure-property relationship) analysis was carried out. An accurate model, based on physico-chemical and structural parameters, was obtained which accounts for more than 95% variations in the relative binding constants. The model confirmed importance of hydrophobic interactions in formation of the indole derivatives/beta-cyclodextrin inclusion complexes. In general, more lipophilic indole derivatives bind more strongly than more polar ones. Hydrogen bonds between the carboxyl group of the indole-3-acetic acids and the hydroxyl groups lining the rim of the binding cavity additionally stabilize the complex. Thus, the indole-3-acetic acids bind to beta-cyclodextrin about ten times stronger than the indolic compounds having hydroxyl (indole-3-ethanol), ester (indole-3-acetic acid methyl ester), acetamide (indole-3-acetamide) or aldehyde (indole-3-acetaldehyde) group at the ring position 3. The length and flexibility of the side chain containing the carboxyl group also affect the affinities of the indole derivatives to beta-cyclodextrin. The binding constants of the unsubstituted indole carboxylic acids increase in the following order: indole-3-carboxylic acid < indole-3-acrylic acid < indole-3-acetic acid < indole-3-propionic acid < indole-3-butyric acid. The lower binding affinities of 2-methyl-5-hydroxyindole-3-acetic acid and 5, 7-dichloroindole-3-acetic acid could be attributed to the steric restrictions of the binding cavity. Whereas esterification of the carboxyl group markedly reduces the binding capacity of the indolic compounds, similarity between the relative binding constants of IAA and its 1-methyl derivative indicates that a free indole NH group is not essential for the binding to beta-cyclodextrin.

binding interactions; indole derivatives; beta cyclodextrin; QSPR

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