Evidence for site-specific intra-ionic hydrogen/deuterium exchange in the low-energy collision-induced dissociation product ion spectra of protonated smallmolecules generated by electrospray ionisation

The experimental investigation of site-specific intra-ionic hydrogen/deuterium (H/D) exchange in the low-energy collisioninduced dissociation (CID) product ion spectra of protonated small molecules generated by electrospray ionisation (ESI) is presented. The observation of intra-ionic H/D exchange in such ions under low-energy CID conditions has hitherto been rarely reported.Thedatasuggest that the intra-ionicH/Dexchangetakes place inasite-specificmannerbetweenthe ionisingdeuteron, localised at either a tertiary amine or a tertiary amine-N-oxide, anda γ-hydrogen relative tothenitrogen atom.Nuclear magnetic resonance (NMR) spectroscopy measurements showed that no H/D exchange takes place in solution, indicating that the reaction occurs in the gas phase. The compounds analysed in this study suggested that electron-withdrawing groups bonded to the carbon atom bearing the γ-hydrogen can preclude exchange. The effect of the electron-withdrawing group appears dependent upon its electronegativity, with lower x value groups still allowing exchange to take place. However, the limited dataset available in this study prevented robust conclusions being drawn regarding the effect of the electron-withdrawing group. The observation of site-specific intra-ionic H/D exchange has application in the area of structural elucidation, where it could be used to introduce an isotopic label into the carbon skeleton of a molecule containing specific structural features. This could increase the throughput, and minimise the cost, of such studies due to the obviation of the need to produce a deuterium-labelled analogue by syntheticmeans. Copyright © 2010 John Wiley & Sons, Ltd.