H-D exchange kinetics of alcohols and protonated peptides: Effects of structure and proton affinity

The kinetics of gas-phase H-D exchange reactions of a series of protonated amino acids and peptides with deuterium-substituted alcohols (D₂O, CH₃OD, C₂H₅OD and 1-C₄H₉OD) 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 (ΔPA = 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 ΔPA. The ability of a peptide and an alcohol to exchange efficiently even when ΔPA 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.