Structural studies of acetylcholine agonists by NMR spectroscopy and theoretical calculations / Estudos estruturais de agonistas de acetilcolina pela espectroscopia de RMN e calculos teoricos

AUTOR(ES)
DATA DE PUBLICAÇÃO

2008

RESUMO

This work describes the conformational analysis of muscarine agonists of acetylcholine (ACh+): carbachol, metacholine and pilocarpine. It was performed from the analysis of 3JHH coupling constants and from ab initio theoretical calculations. Their conformational behavior is discussed taking into account the most important dihedral angles. Both the results from theoretical calculations at B3LYP/6-311+G(d,p) as the experimental data indicated that the gauche conformer is predominant, considering the dihedral angle wich is responsible by their pharmacological activity regardless the solvente employed. The stabilization of the gauche conformer was ascribed to the eletrostatic interaction between the positively charged nitrogen atom and the (OCH2) oxygen atom of the ester fragment. This was confirmed by the N+/O smaller distance for the most stable conformers. In addition, NBO data showed the relevant role of sC5H5 s* C6N7 e sC5H5s* O4C5 hyperconjugative interactions of the gauche conformers. The most stable conformers for the above compounds are: : acetycholine, TG-; carbachol, AG+; methacholine, TG+; pilocarpine, TG+C

ASSUNTO(S)

theoretical calculations calculos teoricos agonistas de acetilcolina acetylcholine agonists rmn rnm analise conformacional conformational analysis

ACESSO AO ARTIGO

Documentos Relacionados