Gas-phase RNA and DNA ions.: 1.: H/D exchange of the [M-H]- anions of nucleoside 5′-monophosphates (GMP, dGMP, AMP, dAMP, CMP, dCMP, UMP, dTMP), ribose 5-monophosphate, and 2-deoxyribose 5-monophosphate with D2O and D2S

H/D exchange from D2O and D2S to electrosprayed [M - H](-) nucleoside 5'-monophosphate anions (GMP, dGMP, AMP, dAMP, CMP, dCMP, UMP, TMP) is examined by Fourier transform ion cyclotron resonance mass spectrometry at 9.4 T, along with sugar phosphate controls (ribose 5-monophosphate (R5P) and 2-deoxyribose 5-monophosphate (dR5P)). The relative exchange rates of the nucleotides with D2O were dR5P > dCMP > R5P > CMP > dAMP > UMP > AMP, dTMP much greater than dGMP much greater than GMP, and with D2S were CMP > UMP approximate to dTMP > dCMP > dAMP > AMP > R5P > dR5P much greater than dGMP much greater than GMP. All exchange rates increase dramatically on changing from D2O to D2S, due to the smaller gas-phase acidity difference between exchange reagent and the nucleotide: Delta(Delta H-acid) > 60 kcal mol(-1) for D2O vs Delta(Delta H-acid) > 20 kcal mol(-1) for D2S. Ab initio calculations on model compounds at the MP2/6-31+G*//HF/6-31+G* level yield the following order of calculated acidities for each of the exchangeable hydrogens: R2O3PO-H > R2N-H > (R2O-H on ribose) > RN-H-2 > (R2O-H on 2-deoxyribose). The present results provide a quantitative measure of proton exchange ratel, in minutes for D2S (rather than hours for D2O) for gas-phase nucleotide anions; thereby opening up a wide range of extensions to chemically modified nucleotides as well as single-stranded and duplex RNAs and DNAs.