A possible origin of [M-nH+mX]((m-n)+) ions (X = alkali metal ions) in electrospray mass spectrometry of peptides

The [M - nH + mX]((m-n)+) (X = alkali metal ion) are common ions in the mas s spectrum of a peptide that is electrosprayed in the presence of an alkali metal salt or hydroxide. The feasibility of forming [M - nH + mX]((m-n)+) ions in the gas phase including those in the lens region of the mass spectr ometer via ion-molecule reactions and/or reactions between components of co llisionally activated adducts was investigated. The Li+ ion was selected fo r examination since its salts are computationally the least expensive among alkali metal salts. The lithium ion affinities of the [M - H]- ions of N-m ethylacetamide, acetic acid, and 1-propanamine were calculated by means of density functional theory (DFT) at various levels of theory, including B3LY P/6-311++G(d, p). These three compounds were selected as representatives of relevant functional groups on a peptide. The calculated lithium ion affini ties, together with evaluated thermochemical data, were used to calculate t he enthalpies of reactions between the model compounds and LiOH, LiCl, and Li(H2O)(+) that might lead to the formation of [M - nH + mX]((m-n)+). A num ber of these reactions were found to be exothermic or slightly endothermic (Delta H degrees < +20 kcal/mol). DFT calculations on the energetics of a m odel reaction revealed a relatively flat potential energy hypersurface cont aining a well of approximately 35 kcal/mol in depth and devoid of significa nt barriers. These results are used to postulate the formation of [M - nH mX](((m-n)+) ions in the gas phase in the ion source and/or in the lens re gion via collisions between an ionic peptide and neutral lithium compounds or collisional activation of lithium-peptide adducts. (C) 1999 Elsevier Sci ence B.V.