Abstract
Low-energy collision-induced dissociation (CID) of acetylcholine (ACh) yields only two fragment ions: the dominant C4H7O +2 ion at m/z 87, arising from trimethylamine loss; and protonated trimethylamine at m/z 60. Since the literature is replete with conflicting mechanisms for the loss of trimethylamine from ACh, in this article density functional theory (DFT) calculations are used to assess four competing mechanisms: (1) Path A involves a neighboring group attack to form a five-membered ring product, 2-methyl-1,3-dioxolan-2-ylium cation; (2) Path B is a neighboring group attack to form a three-membered ring product, 1-methyl-oxiranium ion; (3) Path C involves an intramolecular elimination reaction to form C=O protonated vinylacetate; and (4) Path D is a 1,2-hydride migration reaction forming CH2-protonated vinylacetate. At the MP2/6-311++G(2d,p)//B3-LYP/6-31+G(d,p) level of theory path A is the kinetically favored pathway, with a transition-state energy barrier of 37.7 kcal mol−1 relative to the most stable conformer of ACh. The lowest energy pathway for the formation of protonated trimethylamine was also calculated to proceed via path A, involving proton transfer within the ion-molecule complex intermediate, with the exocylic methyl group being the proton donor. To confirm the site of proton transfer, low-energy CID of acetyl-d 3-choline (d 3-ACh) was carried out, which revealed loss of trimethylamine and the formation of Me3ND+.
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This article is Part 63 of the series “Gas Phase Ion Chemistry of Biomolecules.
Published online September 25, 2008
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Lioe, H., Barlow, C.K. & O’Hair, R.A.J. How does acetylcholine lose trimethylamine? A density functional theory study of four competing mechanisms. J Am Soc Mass Spectrom 20, 238–246 (2009). https://doi.org/10.1016/j.jasms.2008.09.017
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DOI: https://doi.org/10.1016/j.jasms.2008.09.017