Cluster Models of Bioenergetics. 4. Interaction Energies of Acetylcholine With Aromatic and Polar Molecules

Published

October 16, 2008

Author(s)

C A. Deakyne, M Meot-Ner (Mautner)

Abstract

The binding energies of the quaternary ions (CH₃)4N⁺ and acetylcholine (ACh) to neutral molecules have been measured by pulsed high-pressure mass spectrometry and calculated ab initio, to model interactions in the acceptor channel. Binding energies to C₆H₆ and C₆H₅CH₃ are similar to those to H₂O (33 kJ/mol to 42 kJ/mol), but weaker than those to polar ligands such as (CH₃)₂CO and CH₃CO₂CH₃ (50 kJ/mol to 63 kJ/mol) and to amides (up to 84 kJ/mol). These data suggest that aromatic residues that line the groove leading to the ACh receptor site may provide stabilization comparable to water, and therefore allow entry from the aqueus environment, yet do not bind ACh as strongly as polar protein groups, and therefore allow transit, without trapping, to the receptor site. In order to assess the role of ACh conformational changes, five distinct ACh conformers have been examined computationally. Each conformer can form a number of stable complexes with water or benzene. The most stable hydrated structure has a bridge of two water molecules between the quaternary moiety and the carbonyl oxygen of ACh. After transit through the channel the aromatic environment may play a role when formation of the active all-trans ACh rotamer is required. The calculations show that the aromatic environment may decrease the energy barrier to the formation of this active rotamer, which is required at the receptor site.

Citation

Journal of Physical Chemistry

Pub Type

Journals

Keywords

acetylcholine, clusters, gas phase, hydrogen bonds, ion thermochemistry, mass spectrometry

Citation

Deakyne, C. and Meot-Ner (Mautner), M. (2008), Cluster Models of Bioenergetics. 4. Interaction Energies of Acetylcholine With Aromatic and Polar Molecules, Journal of Physical Chemistry (Accessed April 30, 2024)