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Models for molecular mechanisms in drug—receptor interactions. Serotonin and 5‐hydroxyindole complexes with imidazolium cation
Author(s) -
Weinstein Harel,
Osman Roman
Publication year - 2009
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560120726
Subject(s) - chemistry , molecule , pseudopotential , interaction energy , tryptamine , tryptamines , ab initio , polarization (electrochemistry) , computational chemistry , chemical physics , stereochemistry , organic chemistry , atomic physics , biochemistry , physics
The interaction of 5‐hydroxytryptamine and 5‐hydroxyindole with theimidazolium cation is studied in the light of previously obtained reactivity characteristics of indolealkylamines in order to identify molecular determinants for the interaction of tryptamines with biological receptors. The complexes are calculated by a pseudopotential method. Results from this method are shown to be in excellent agreement with ab initio calculations on the separated molecules. At an interplanar interaction distance of 3.3 Å, suggested by crystallographic studies on the complexes of serotonin, the interaction is found to be mainly electrostatic: the transfer of charge to the imidazolium cation is negligible; the mutual polarization of the molecule is the major component of the electron charge redistribution. The degree of polarization affects the stabilization energy of the complex and is dependent on the mutual orientation of the molecules. The favorable orientation coincides with the interaction geometry predicted by electrostatic reactivity criteria derived for the separated molecules. The nature and localization of the stabilizing polarization serves as a first indication of the possible electronic mechanisms involved in the triggering of a biological receptor by drugs from the tryptamine series.