Formation of [M - nH] + mNA](m-n)+ and [M - nH + mK](m-n)+ ions in electrospray mass spectrometry of peptides and proteins.

The [M - nH + mNa](m-n)+ and [M - nH + mK](m-n)+ ions are common in the electrospray mass spectra of proteins and peptides. The feasibility of forming these ions in the gas phase via collision activation and/or ion-molecule reaction is investigated. Sodium and potassium affinities of the N-methylacetamide anion, the acetate anion, and the 1-propanamide anion have been calculated using density functional theory at the B3LYP/6-311+ +G(d,p) level of theory. These anions were chosen as models for the functional groups on a protein or peptide. These affinity values are then used to calculate reaction enthalpies of alkali hydroxides, chlorides, and hydrates with N-methylacetamide, acetic acid, the acetate anion, and 1-propanamine, model reactions that may lead to formation of the [M - nH + mNa](m-n) and [M - nH + mK](m-n)+ ions. It is found that a number of these reactions are exothermic or slightly endothermic (deltaH(o) < + 20 kcal/mol) and are accessible after collision activation in the lens region. The potential energy hypersurfaces of model reactions between NaOH and formamide as well as NaCl and formamide show relatively flat surfaces devoid of significant barriers.