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

Abstract

The [M - nH + mX] (m-n)+ (X = alkali metal ion) are common ions in the mass 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 spectrometer via ion-molecule reactions and/or reactions between components of collisionally activated adducts was investigated. The Li + ion was selected for examination since its salts are computationally the least expensive among alkali metal salts. The lithium ion affinities of the [M - H] - ions of N-methylacetamide, acetic acid, and 1-propanamine were calculated by means of density functional theory (DFT) at various levels of theory, including B3LYP/6-311++G(d, p). These three compounds were selected as representatives of relevant functional groups on a peptide. The calculated lithium ion affinities, together with evaluated thermochemical data, were used to calculate the enthalpies of reactions between the model compounds and LiOH, LiCl, and Li(H 2O) + that might lead to the formation of [M - nH + mX] (m-n)+. A number of these reactions were found to be exothermic or slightly endothermic (ΔH° < +20 kcal/mol). DFT calculations on the energetics of a model reaction revealed a relatively flat potential energy hypersurface containing a well of approximately 35 kcal/mol in depth and devoid of significant 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 region via collisions between an ionic peptide and neutral lithium compounds or collisional activation of lithium-peptide adducts. © 1999 Elsevier Science B.V.