A possible origin of [M - n H + m X]
( m-n ) +
ions (X = alkali
metal ions) in electrospray mass spectrometry of peptides
Christopher F. Rodriquez, Rene ´ Fournier, Ivan K. Chu, Alan C. Hopkinson,
K.W. Michael Siu*
Department of Chemistry, York University, 4700 Keele Street, Toronto, Ontario M3J 1P3, Canada
Received 26 January 1999; accepted 10 May 1999
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
2
O)
+
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
( H°+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. (Int J
Mass Spectrom 192 (1999) 303–317) © 1999 Elsevier Science B.V.
Keywords: Adduct ions; Alkali metal; Peptide; Collisional activation
1. Introduction
The sodium ion is an ubiquitous contaminant of
samples in electrospray mass spectrometry. For pep-
tide samples, the presence of high concentrations of
Na
+
typically results in envelopes of ions of [M -
nH + mNa]
( m-n) +
in the positive ion detection
mode, where n is the number of protons abstracted
from the peptide M, and m is the number of sodium
ions incorporated [1,2]. For a given charge state, i.e.
constant ( m - n) +, the peptide containing peaks are
readily identified by their separation on the m/z axis
by (23 - 1)/( m - n) units; however, the presence of
a large number of sodium-containing adducts of the
peptide crowds the mass spectrum and decreases
sensitivity as the peptide signal is distributed among
many peaks, and is generally considered to be a * Corresponding author. E-mail: kwmsiu@yorku.ca
1387-3806/99/$20.00 © 1999 Elsevier Science B.V. All rights reserved
PII S1387-3806(99)00116-5
International Journal of Mass Spectrometry 192 (1999) 303–317