Structural features and protonation site of epibatidine in the gas phase: an investigation through infrared multiphoton dissociation spectroscopy and computational chemistry.
The gas phase structures of epibatidine, one of the most potent agonists of nicotinic acetylcholine receptors (nAChRs), are determined by means of infrared multiphoton dissociation (IRMPD) spectroscopy and quantum chemistry calculations. Comparison of the experimental and theoretical spectra provides evidence that about 15% of epibatidine is protonated on the Nsp(2) nitrogen in the gas phase. In contrast, the computational study of deschloroepibatidine shows that in the gas phase, the molecule is present only protonated on the Nsp(2) nitrogen. The main minima of the Nsp(2) protonated forms of the two molecules are strongly stabilized by intramolecular CH···Nsp(3) hydrogen bonds. The fundamental insights obtained in the present study on these two important nAChRs agonists show how subtle chemical modifications can have a deep impact on important physicochemical properties.
Laboratoire CEISAM, UMR CNRS 6230, Faculté des Sciences et des Techniques, Université de Nantes, 2, rue de la Houssinière, BP 92208, Nantes F-44322 Cedex 3, France.
Alexandre P
AP
Atkinson
Aurélien
A
Planchat
Jérôme
J
Graton
Eric
E
Renault
Gilles
G
Grégoire
Jean-Yves
JY
Le Questel
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D019295:Computational Biology; D005740:Gases / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011522:Protons; D011725:Pyridines / Q000737:chemistry*; D013055:Spectrophotometry, Infrared
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005740:Gases; D011522:Protons; D011725:Pyridines; C507197:deschloroepibatidine; C082748:epibatidine