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

Molecules. 2020 Feb 5;25(3):670. doi: 10.3390/molecules25030670.


Acetylcholine, which is associated with Alzheimer's disease, is widely known to have conformers. The preference of each conformer to undergo neutral hydrolysis is yet to be considered. In this study, we employed density-functional calculations to build the conformers and investigated their preference in one-step neutral hydrolysis. The results showed the preference in ten possible hydrolysis pathways involving seven acetylcholine conformers (reactant), four transition state structures, and two choline conformers (product). Three out of the seven acetylcholine conformers predicted from the results confirmed experimental findings on the conformers stability. We suggested that two out of ten possible pathways were observed in the experimental results based on agreement in reaction energy. Eventually, this study will emphasize the importance of considering acetylcholine conformers in its hydrolysis study.

Keywords: acetylcholine; conformational preference; density functional theory; neutral hydrolysis.

MeSH terms

  • Acetylcholine / analogs & derivatives
  • Acetylcholine / chemistry*
  • Alzheimer Disease
  • Density Functional Theory
  • Humans
  • Hydrogen Bonding
  • Hydrolysis
  • Molecular Conformation*
  • Neurotransmitter Agents / chemistry*
  • Synaptic Transmission / physiology*
  • Thermodynamics


  • Neurotransmitter Agents
  • Acetylcholine