Abstract
Ethylnitrilium ion can be generated by protonation of acetonitrile (when used as the LC-MS mobile phase) under the conditions of atmospheric pressure ionizations, including electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) as well as atmospheric pressure photoionization (APPI). Ethylnitrilium ion (\(CH_3 - C \equiv \mathop N\limits^ + H\) and its canonical form \(CH_3 - \mathop C\limits^ + = NH\)) is shown to efficiently undergo the gas-phase Meerwein reaction with epoxides. This reaction proceeds by the initial formation of an oxonium ion followed by three-to-five-membered ring expansion via an intramolecular nucleophilic attack to yield the Meerwein reaction products. The density functional theory (DFT) calculations at the B3LYP/6-311 + G(d,p) level show that the gas-phase Meerwein reaction is thermodynamically favorable. Collision-induced dissociation (CID) of the Meerwein reaction products yields the net oxygen-by-nitrogen replacement of epoxides with a characteristic mass shift of 1 Da, providing evidence for the cyclic nature of the gas-phase Meerwein reaction products. The gas-phase Meerwein reaction offers a novel and fast LC-MS approach for the direct analysis of epoxides that might be of genotoxic concern during drug development. Understanding and utilizing this unique gas-phase ion/molecule reaction, the sensitivity and selectivity for quantitation of epoxides can be enhanced.
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Wu, L., Liu, D.Q. & Kord, A.S. Gas-phase Meerwein reaction of epoxides with protonated acetonitrile generated by atmospheric pressure ionizations. J Am Soc Mass Spectrom 21, 1802–1813 (2010). https://doi.org/10.1016/j.jasms.2010.06.017
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DOI: https://doi.org/10.1016/j.jasms.2010.06.017