A theoretical study of epibatidine

A theoretical study of the conformational profile of epibatidine and its protonated form has been carried out using molecular mechanics (CVFF and CFF91), semiempirical (AM1) and ab initio (RHF/6-31G* and B3LYP/6-31G*) methods. Six minima have been found for the neutral molecule and four for the protonated one with small rotational barriers between them. The stability of the minima has been explained using the AIM methodology. Finally, the NMR shieldings of the different conformers found have been calculated with the GIAO method and used to assign some of the ambiguous experimental signals.

[1]  José Elguero,et al.  Non-conventional hydrogen bonds , 1998 .

[2]  D. Anderson,et al.  Mono- and disubstituted-3,8-diazabicyclo[3.2.1]octane derivatives as analgesics structurally related to epibatidine: synthesis, activity, and modeling. , 1998, Journal of medicinal chemistry.

[3]  J K Lynch,et al.  Neuronal nicotinic acetylcholine receptors as targets for drug discovery. , 1997, Journal of medicinal chemistry.

[4]  R. Bader,et al.  Identifying and Analyzing Intermolecular Bonding Interactions in van der Waals Molecules , 1996 .

[5]  J. Malpass,et al.  Synthesis of epibatidine homologues: Homoepibatidine and bis-homoepibatidine , 1996 .

[6]  M. Trudell,et al.  Chemistry of 7-Azabicyclo[2.2.1]hepta-2,5-dienes, 7-Azabicyclo[2.2.1]hept-2-enes, and 7-Azabicyclo[2.2.1]heptanes. , 1996, Chemical reviews.

[7]  D. Donnelly-roberts,et al.  Novel 3-Pyridyl ethers with subnanomolar affinity for central neuronal nicotinic acetylcholine receptors. , 1996, Journal of medicinal chemistry.

[8]  G. Blaskó,et al.  A practical route to epibatidine , 1994 .

[9]  A. Becke Density-functional thermochemistry. III. The role of exact exchange , 1993 .

[10]  L. Pannell,et al.  Epibatidine: a novel (chloropyridyl)azabicycloheptane with potent analgesic activity from an ecuadoran poison frog , 1992 .

[11]  P. Petillo,et al.  The nitrogen inversion barrier of 7-methyl-7-azabicyclo[2.2.1]heptane and the "bicyclic effect" , 1989 .

[12]  R. Bader,et al.  Prediction of the structures of hydrogen-bonded complexes using the laplacian of the charge density , 1988 .

[13]  Parr,et al.  Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density. , 1988, Physical review. B, Condensed matter.

[14]  R. Sheridan,et al.  The ensemble approach to distance geometry: application to the nicotinic pharmacophore. , 1986, Journal of medicinal chemistry.

[15]  Eamonn F. Healy,et al.  Development and use of quantum mechanical molecular models. 76. AM1: a new general purpose quantum mechanical molecular model , 1985 .

[16]  R. Ditchfield,et al.  Self-consistent perturbation theory of diamagnetism , 1974 .

[17]  W. H. BEERS,et al.  Structure and Activity of Acetylcholine , 1970, Nature.

[18]  R. Bader Atoms in molecules : a quantum theory , 1990 .