The use of dicationic ion-pairing compounds to enhance the ambient detection of surface lipids in positive ionization mode using desorption electrospray ionisation mass spectrometry

Abstract

RATIONALE:Lipids are typically analysed in negative ionisation mode in desorption electrospray ionisation mass spectrometry (DESI-MS), which can result in reduced sensitivity. In this study we examine the use of dicationic compounds as reactive DESI-MS agents to detect a range of lipid standards from the surface in positive ionisation mode. METHODS: Nine dicationic compounds were tested for their ability to detect seven representative lipid species (palmitoleic acid, linoleic acid, phosphatidic acid (34:1), phosphoethanolamine (34:2), phosphatidylglycerol (34:1), phosphatidylserine (36:1), and phosphoinositol (34:2)) with a 2D DESI source on hydrophobic surfaces. Two different solvent systems (methanol/chloroform (1:1) and methanol) were tested with each dicationic compound, with the DESI-MS analysis performed in the positive ionisation mode. RESULTS: Most of the dications tested were able to form stable ion-pairs with the negatively charged lipid species when analysed from the surface with DESI-MS, and were detected readily in positive ionisation electrospray mode as singly charged species. The optimal solvent system was found to be methanol. The dicationic compound [C 6 (C 1 Pyrr) 2 ][Br] 2 was found to enhance the detection of palmitoleic acid (638%), linoleic acid (304%) and phosphoethanolamine (269%) compared with the negative ionisation mode. CONCLUSIONS: We demonstrate the first successful application of dicationic compounds in DESI-MS for the ambient surface detection of model lipids in positive electrospray ionisation mode. Dicationic compounds could potentially be used as reactive DESI-MS agents to improve the ambient detection of a number of negatively charged analytes.

High-Resolution Ambient MS Imaging of Negative Ions in Positive Ion Mode: Using Dicationic Reagents with the Single-Probe

“…[C 5 (bpyr) 2 ] 2+ was able to form adducts with a broad range of negatively charged metabolites, and this dication does not seem to favor any particular mass range. This observation is in contrast with previous DESI-MSI studies, in which dicationic compound [C 6 (C 1 Pyrr) 2 ][Br] 2 [41, 42] was chosen as the reagent, where the higher mass ranges were less well detected. It is very likely that the difference of detection range resulted from the difference of sampling and ionization mechanisms between the Single-probe MSI and DESI-MSI techniques.…”

“…This concentration is higher than those used in previous LC-PIESI MS (40 µM) [40] and DESI-MS (10 µM) [41] studies. It is likely that in our MSI experiments, a larger amount of complex molecules extracted from biological tissues can form adducts with the dicationic compounds resulting in higher consumptions of dicationic reagents.…”

“…In addition to the ESI-MS experiments, dicationic compounds have been applied for ambient surface analyses. A number of dicationic compounds were used in DESI MS for the detection of stock lipid species spotted onto a glass surface, where one of the dicationic compounds [C 6 (C 1 Pyrr) 2 ][Br] 2 was show to have selectively improved the detection of palmitoleic acid and linoleic acid over their detection in the negative ionization mode [41]. [C 6 (C 1 Pyrr) 2 ][Br] 2 was later applied to DESI MSI studies on biological tissues, where adducts of dicationic compound with fatty acids in the range of m/z 250–350 were observed in the positive ionization mode [42].…”

Easily fabricated ion source for characterizing mixtures of organic compounds by direct analysis in real time mass spectrometry

“…These experiments can differ from those seen with DART with the involvement of either covalent derivatization, such as xed charge derivatization with betaine aldehyde 50 and ketone modication with hydroxylamine, 54 or non-covalent complexation, such as dicationic pairing 51,52 and other supramolecular host-guest complexes.…”

“…That method involves host-guest supramolecular chemistry with either the host or guest in the spray to complex with a target functionality present on the analyte in the sample, or derivatization chemistry involving attachment of a xed charge to the target functionality within the molecule, oen with the reagent molecule being delivered in the spray. 50 Many different hostguest supramolecular interactions [51][52][53] and chemical derivatization methods 50,54 have been used successfully with reactive DESI. We report in this study a similar method with DART ionization, referred to as reagent assisted desorption ionization (RADI), with which the introduction of host-guest supramolecular chemistry allows for enhanced detection of target species in a complex mixture and simplication of resultant spectra.…”