Conformational analysis of the C(6)-O(1)-C(5)-C(4) fragment in acetylcholine by carbon-13 NMR spectroscopy

Cassidei, L.; Sciacovelli, O.

doi:10.1021/ja00394a034

Cited by 22 publications

(14 citation statements)

References 7 publications

(9 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This result is in disagreement with a series of experimental studies [7,8,19,20] in which it was observed that the s 2 dihedral is often in the gauche conformation. The reason for which the gauche conformation should be favoured was justi®ed by invoking that``ACh + can be considered a member of a class of 1,2-disubstituted ethanes in which the increased stability of the gauche conformation is the norm.…”

Section: In Vacuocontrasting

confidence: 98%

Molecular dynamics, density functional and second-order Møller-Plesset theory study of the structure and conformation of acetylcholine in vacuo and in solution

Marino

Russo

Tocci

et al. 2001

Theoretical Chemistry Accounts: Theory, Computation, and Modeli

View full text Add to dashboard Cite

Molecular mechanics minimizations based on the CVFF force ®eld and molecular dynamics simulation for a time of 2.5 ns were performed to examine the conformational behaviour and the molecular motion of acetylcholine in vacuo and in aqueous solution. Five low-lying conformations, namely the TT, TG, GG, G*G and GT, were obtained from molecular mechanics computations with the GT structure as the absolute minimum. Molecular dynamics trajectories in vacuo and in water show that only four (GT, GG, G*G and TG) and three (TG, TT and GT) conformations are present in the simulation time, respectively. Density functional B3LYP and second-order Mùller± Plesset (MP2) methods were then used to study all the ®ve lowest-lying conformers of acetylcholine neurotransmitter in vacuo and in water by the polarizable continuum model approach. The B3LYP and MP2 computations show that in the gas phase all minima lie in a narrow range of energy with the G*G conformer as the most stable one. The relative minima GG, GT, TG and TT are located at 1.1 (3.3), 1.8 (4.2), 2.1 (4.5) and 4.3 (7.3) kcal/mol above the absolute one at the B3LYP (MP2) level. The preferred conformation in water is the TG. Solvation reduces the relative energy dierences between the ®ve minima in both computations.

show abstract

Section: In Vacuocontrasting

confidence: 98%

Molecular dynamics, density functional and second-order Møller-Plesset theory study of the structure and conformation of acetylcholine in vacuo and in solution

Marino

Russo

Tocci

et al. 2001

Theoretical Chemistry Accounts: Theory, Computation, and Modeli

View full text Add to dashboard Cite

show abstract

“…13CNMR experiments have shown that the dihedral angle, D 2, may attain both a gauche and a trans conformation in aqueous solution, with a rotamer population of 0.335/0.665 (Cassidei and Sciacovelli, 1981). However, the free-energy difference between these rotamers was calculated to be less than 0.5 kcal/mol, based on the rotamer population.…”

Section: Discussionmentioning

confidence: 99%

“…~3C NMR experiments have confirmed that the dihedral angle, D 2, may attain either a trans or a gauche position, and have indicated that the energy difference between these conformations is less than 0.5 kcal/mol (Cassidei and Sciacovelli, 1981). Other NMR experiments have demonstrated a maximum energy barrier of 7.9 kcal/mol for rotation about dihedral D 3 (Fig.…”

Section: Introductionmentioning

confidence: 87%

Molecular structure and dynamics of acetylcholine

Edvardsen

Dahl

1991

J. Neural Transmission

View full text Add to dashboard Cite

Molecular dynamics simulations and energy calculations based on the AMBER force field were used to examine the molecular movements and low-energy conformations of acetylcholine in vacuum and in aqueous solution. Electronic structures of acetylcholine were calculated by ab initio quantum mechanical calculations. Three conformations obtained from crystal structures and two from previous calculations were used as starting geometries in the simulations. The trans, gauche conformer had lowest energy both in vacuum and in aqueous solution. Both trans, gauche and trans, trans conformers were observed during molecular dynamics in water, which indicates that both conformations are relatively stable. The acetyl methyl group rotated more rapidly than those at the nitrogen atom during molecular dynamics simulations in water. Correlation times of both types of methyl groups were in good agreement with NMR data, which demonstrates that such simulations provide valid information about molecular movements of the neurotransmitter.

show abstract

“…To understand the interactions of biologically interesting molecules, it is necessary to know the shape of the interaction sites as well as the conformations of the interacting molecules and, the conformational analysis of Ach has been subject of many experimental 6–25 and theoretical 26–46 investigations. Aspects of the Ach potential energy surface (PES) have been the subject of numerous experimental investigations including X‐Ray 6–8, 16–21, NMR 9, 11–14, 23, 25, electron diffraction 22, and Raman Spectroscopy 15, in addition, computational studies have employed ab initio 3, 31, 34, 35, 42–44, semi empirical and empirical methods 26–30, 38, 39 as well as molecular dynamics 36, 37, 45.…”

Section: Introductionmentioning

confidence: 99%

A DFT study of determination of the reactive sites of the acetylcholine and its agonists: In the gas phase and dielectric medium

Serdaroğlu

2011

Int J of Quantum Chemistry

View full text Add to dashboard Cite

The reactive behavior of acetylcholine and its agonist molecules have been investigated using B3LYP hybrid density functional method at the 6-311þþG** basis set level, in the gas phase and aqueous phase. The calculations have been performed to obtain optimized geometries, relative reactivities, net atomic charges, HOMO, and LUMO energies. The solvent effect has been analyzed by using the continuum model (IPCM) and, the obtained results have shown that the all molecules have been stabilized more by solvent dielectric constant. For Ach and its analogues, it has been very well known that esteratic site and quaternary ammonium group which have reflected the difference in biological activity have been the two of the most important active site for interactions between molecule and its receptor. The structures of these analogues have provided an essential foundation for subsequent structureactivity analysis of ligand binding at acetylcholine receptors, neuronal uptake inhibitors and transporters. Molecular modeling predictions will be important initial steps toward the development of novel pharmaceuticals in the fight acetylcholine-related neurological disorders. This work is therefore expected to facilitate the design and development of new biologically active Ach analogues to treat Ach-related neurological disorders and, specially is used to qualitative understanding of the reactivity and related properties and, so on can be used to a preselection of new ligands which at the moment is taken essentially from empirical knowledge. V

show abstract

Conformational analysis of the C(6)-O(1)-C(5)-C(4) fragment in acetylcholine by carbon-13 NMR spectroscopy

Cited by 22 publications

References 7 publications

Molecular dynamics, density functional and second-order Møller-Plesset theory study of the structure and conformation of acetylcholine in vacuo and in solution

Molecular dynamics, density functional and second-order Møller-Plesset theory study of the structure and conformation of acetylcholine in vacuo and in solution

Molecular structure and dynamics of acetylcholine

A DFT study of determination of the reactive sites of the acetylcholine and its agonists: In the gas phase and dielectric medium

Contact Info

Product

Resources

About