Stability and Interconversion of Acetylcholine Conformers

Abstract

The gas phase structures, energetics, and interconversion pathways of five lowest energy conformers of acetylcholine were examined employing the B3LYP, MP2, and CCSD(T) methods in conjunction with diverse basis sets including the correlation consistent aug-cc-pVDZ and aug-cc-pVTZ basis sets. It is found that use of adequate basis set containing proper polarization and diffuse functions capable of describing the floppy potential energy surface of acetylcholine is important in correctly predicting the relative stability of these conformers. The interconversion pathways and barrier heights between these conformers were elucidated by examining the potential energy surface for torsional motion, which also manifested the presence of chiral conformations of acetylcholine corresponding to the original conformations. On the basis of high level electronic energy calculations and thermal contribution analysis, four lowest energy conformers appear to be populated in the energy range of less than 1 kcal/mol at room temperature.

Acetylcholine Conformational Flexibility and Its Neutral Hydrolysis in Aqueous Solution

“…In recent decades, computational studies on ACh conformational properties in aqueous solution have dominated. They aim to determine the reactive sites of ACh conformers, [28] the conformational changes’ pathway, [29] the fluorination effect to conformational changes, [30] hydration features, [31] and the features of ACh conformers paired to ions in biological media [32] . In our previous work, we demonstrated that two groups of ACh conformers, capable of undergoing hydrolysis without being preceded by conformational changes, have an energy difference of 8 kcal/mol [33] .…”

A Density-Functional Study of the Conformational Preference of Acetylcholine in the Neutral Hydrolysis

“…The dependency is stronger when the reaction involves an enzyme as a catalyst [14,15]. In the ACh + case, at least three conformers have been investigated to understand their stability and the interconversion among the conformers and to explore the fluorination and solvent effects on each of them [16][17][18][19][20][21][22][23][24][25][26][27]. However, to the best of our knowledge, studies of ACh + conformers remain limited to its stability as an individual molecule.…”