Oligosaccharide analysis using anion attachment in negative mode electrospray mass spectrometry

Abstract

Eleven different anionic species were able to form adducts with neutral oligosaccharides at low cone voltage in negative ion mode electrospray mass spectrometry. Among them, fluoride and acetate have the ability to significantly enhance the absolute abundance of [M - H](-) for neutral oliogosaccharides, which otherwise have low tendencies to deprotonate due to the lack of a highly acidic group. Evidence shows that the source of high abundances of [M - H](-) for neutral oligosaccharides arises from the decomposition of [M + F](-) and [M + Ac](-) with neutral losses of HF and HAc, respectively. The chloride adducts have the best stability among all the adduct species investigated, and chloride adducts consistently appeared in higher abundances relative to [M - H](-). In tandem mass spectrometry (ES-MS/MS) experiments, upon collision induced dissociation (CID), F(-) and Ac(-) adducts gave purely analyte-related product ions, i.e., no detection of the attaching anion and no incorporation of these anions into decomposition products. Cl(-) adducts produced both Cl(-) and analyte-related product ions. For the above three anions, CID of adduct species may be used for structural determination of neutral oligosaccharides because, in each case, structurally-informative fragment ions were produced. In the presence of F(-) and Ac(-), simultaneous detection of acidic and neutral oligosaccharides was achieved, because the problem of the presence of an acidic group that can impede the deprotonation of a neutral oligosaccharide was minimized. The ratio of Cl(-):non-Cl-containing product ions obtained in CID spectra of chloride adducts of disaccharides was used to differentiate anomeric configurations of disaccharides. Density functional theory (DFT) was employed to evaluate the optimized structures of chloride adducts of disaccharides, and it was found that chloride anions favor close contact with the hydrogen from the anomeric hydroxyl group. Multiple hydrogen bonding further stabilizes the chloride adduct.

Novel Fragmentation Pathways of Anionic Adducts of Steroids Formed by Electrospray Anion Attachment Involving Regioselective Attachment, Regiospecific Decompositions, Charge-Induced Pathways, and Ion–Dipole Complex Intermediates

“…Our previous experience with electrospray anion attachment targeting neutral compounds [43][44][45][46][47][48][49][50][51][52] led us to examine the possibility of creating anionic adducts of neutral steroids with different anions and, subsequently, studying the fragmentation patterns. Formation of the deprotonated molecule is a two-step procedure in which the neutral precursor first reacts with anion to form the anionic adduct, [M+anion] -followed by decomposition of this adduct under collision to form [ [44].…”

Solid-phase fluorescence and ionization efficiency in negative-ion matrix-assisted laser desorption/ionization of neutral oligosaccharides: Interaction between β-carboline matrix and ammonium salt

“…Cole et al [4,[17][18][19] used ESI MS to study the affinity of chloride anions for neutral oligosaccharides [17][18][19], and the generation and decomposition of chloride-anionized molecules in MALDI MS [4]. Only a small, often comparable amount of ammonium chloride to that of the analyte was required for the generation of chlorideanionized molecules in ESI [18], and the existing conditions were thought to be efficient in MALDI [4].…”

Differentiation of the Stereochemistry and Anomeric Configuration for 1-3 Linked Disaccharides Via Tandem Mass Spectrometry and 18O-labeling

“…For example, CID spectra of deprotonated di-and oligosaccharide alkoxy anions in the negative ion mode showed distinguishable fragmentation patterns for each linkage position, which was successfully applied to di-, tri-, and hexasaccharides [14][15][16][17]. Negative ion adducts [18,19] and positive adducts [20,21] of deprotonated di-and oligosaccharides have also enabled linkage positions to be determined, both in the negative and positive ion modes, and linkage sites can be established for neutral disaccharides as positive ion adducts of lithium or sodium ions or as protonated adducts [22][23][24][25][26][27]. Determination of anomeric configuration has been demonstrated for underivatized disaccharides in the negative ion mode [15,17,18], for derivatized 1-4-and 1-6-linked disaccharides [28], and in the positive ion mode with alkali metals [22][23][24][25][26][27] and lead cationization [20].…”