Conformational analysis of N-protonated-?-fluoro-?-vinyl-ethylamine, a protonated adrenaline model: an exploratory first-principle computational study

Dong Jin Lee, David H Setiadi, Imre G Czismadia

Abstract


The conformational landscapes of N-protonated-?-fluoro-?-vinyl-ethylamine, a fragmented model of L-adrenaline, were explored by full geometry optimization. The study was performed using restricted Hartree-Fock (RHF) formalism with a 3-21 contracted Gaussian (3-21G) basis set (RHF/3-21G level of theory). A complete conformational study of N-protonated-?-fluoro-?-vinyl-ethylamine was carried out from first principles of quantum mechanical computations using the Gaussian 03 (G03) program. The present study was designed to analyze the conformational characteristics of the molecule, a prerequisite to any full investigation of the adrenaline molecule. The relative energies of the various stable conformers of N-protonated-?-fluoro-?-vinyl-ethylamine were calculated for the R and S stereoisomers. For the R stereoisomer, the g-g+ was the most stable and the g+g+ conformer was the least stable. For the S stereoisomer, the g+g- and g-g- were the most and the least stable conformers, respectively. Through the combination analysis of both point and axis chirality, the enantiomeric and diastereomeric relationships of the twelve structures investigated were established. This study presents a preview of all existing stable conformers of adrenaline. Future studies must aim to computationally dock these conformers to the active site of the adrenergic receptor in order to determine which conformer has the greatest biological effect.

Keywords


adrenaline model; conformational study; first-principle quantum chemistry; ?-fluoro-?-vinyl-ethylamine; molecular computation

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