Abstract
The kinetics of gas‐phase HD exchange reactions of a series of protonated amino acids and peptides with deuterium‐substituted alcohols (D~2~O, CH~3~OD, C~2~H~5~OD and 1‐C~4~H~9~OD) were studied in an external source Fourier transform mass spectrometer. The number of exchanges observed on the time‐scale of these experiments ranged from one to the total number of ‘labile’ substrate hydrogens, depending on the amino acid and the deuterating reagent. Exchange efficiencies, k/k~ADO~, varied from <0.001 to 0.3. Within the series ROD, the reactivity increased with increasing size of the R group. For the amino acids with alkyl side‐chains, a roughly linear correlation of log(k/k~ADO~) with proton affinity difference (Δ__PA__ = PA of unprotonated substrate ‐ PA of reagent) was observed. The amino acids lysine and histidine and the dipeptides alanylglycine and diglycine showed higher reactivity and greater tendency for multiple exchange, with a weaker dependence on Δ__PA__. The ability of a peptide and an alcohol to exchange efficiently even when Δ__PA__ is larger is attributed to the occurrence of exchange within a cyclic hydrogen‐bonded complex, in which the deuterating agent forms a bridge between the site of protonation and a basic site on the substrate.