Cluster Models of Bioenergetics. 4. Interaction Energies of Acetylcholine With Aromatic and Polar Molecules
C A. Deakyne, M Meot-Ner (Mautner)
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.
Journal of Physical Chemistry
acetylcholine, clusters, gas phase, hydrogen bonds, ion thermochemistry, mass spectrometry
and Meot-Ner (Mautner), M.
Cluster Models of Bioenergetics. 4. Interaction Energies of Acetylcholine With Aromatic and Polar Molecules, Journal of Physical Chemistry
(Accessed February 29, 2024)