Identification of Protonated Sulfone and Aromatic Carboxylic Acid Functionalities in Organic Molecules by Using Ion–Molecule Reactions Followed by Collisionally Activated Dissociation in a Linear Quadrupole Ion Trap Mass Spectrometer

Abstract

Gas-phase reactivity of protonated model compounds with different functional groups toward trimethoxymethylsilane (TMMS) was studied to explore the utility of this reagent in mass spectrometric identification of specific functionalities for potentially rapid characterization of drug metabolites. Only protonated analytes with a carboxylic acid, a sulfone, or a sulfonamide functionality formed diagnostic adducts that had lost a methanol molecule upon reactions with TMMS. Collisionally activated dissociation (CAD) of these methanol-eliminated adduct ions (MS experiments) produced characteristic fragment ions of m/z 75, 105, and 123 for sulfones, while an additional methanol elimination was observed for carboxylic acids and sulfonamides. CAD of latter products (MS experiments) resulted in elimination of diagnostic neutral molecules CO (44 Da) and CHOSi (90 Da) for aromatic carboxylic acids. Both aliphatic carboxylic acids and sulfonamides yield several fragment ions in these MS experiments that are different from those observed for sulfones or aromatic carboxylic acids. Potential energy surfaces were calculated (at the M06-2X/6-311++G(d,p) level of theory) to explore the mechanisms of various reactions. In summary, sulfones and aromatic carboxylic acids can be differentiated from each other and also from sulfonamides and aliphatic carboxylic acids based on reactions with TMMS and one or two CAD experiments. Aliphatic carboxylic acids and sulfonamides could not be differentiated from each other.

Advanced tandem mass spectrometry in metabolomics and lipidomics—methods and applications

“…Reaction of lipid ions with hydrogen atoms and radical oxygen species resulted in formation of metastable lipid radical ions revealing DB positions and snisomer abundances upon activation. In other experiments, Kenttämaa and co-workers have shown that BF 3 or trimethoxymethylsilane can track the presence of adjacent functional groups in glucuronide [98] or sulfone/carboxylic acid/sulfonamide [99] groups after ion/molecule reactions, respectively. For example, Niyonsaba et al investigated negatively charged drugs ion/molecule reaction mass spectrometry.…”

Graph Based Machine Learning Interprets Diagnostic Isomer-Selective Ion-Molecule Reactions in Tandem Mass Spectrometry

“…Previously, the proton affinity (PA) of an analyte was used to predict whether the protonated analyte would undergo diagnostic product formation or proton transfer or if there is no reaction. 28,29 These proton affinity values were then compared to that of MOP to hypothesize whether a diagnostic product ion would be formed over no reaction or proton transfer from the protonated analyte to MOP. 8 If the PA of the analyte is lower than that of MOP, proton transfer usually dominates.…”

Effects of Residual Water in a Linear Quadrupole Ion Trap on the Protonation Sites of 4-Aminobenzoic Acid

“…8−10 Furthermore, it may also complicate the identification of functional groups in protonated analytes via functional-group selective gas-phase ion−molecule reactions as different protomers may exhibit different reactivities. 11,12 In this context, extensive research has been carried out to better understand the influence of solvents and other variables on the protonation sites of 4-aminobenzoic acid upon electrospray ionization (ESI) in tandem mass spectrometry. 2,6,13−15 When 4-aminobenzoic acid is protonated on the amino nitrogen, the charge is localized on the amino group, which facilitates solvation in the liquid phase.…”