Charge Inversion of Mono- and Dianions to Cations via Triply Charged Metal Complexes: Application to Lipid Mixtures

Abstract

Electrospray ionization (ESI) of mixtures can give rise to ions with different masses and charges with overlapping massto-charge (m/z) ratios. Such a scenario can be particularly problematic for the detection of low-abundance species in the presence of more highly abundant mixture components. For example, negative mode ESI of polar lipid extracts can result in highly abundant singly charged glyerophospholipids (GPLs), such as phosphatidylethanolamines (PE) and phosphatidylglycerols (PG), that can obscure much less abundant cardiolipins (CLs), which are complex phospholipids with masses roughly double those of GPLs that mostly form doubly charged anions. Despite their low relative abundance, CLs are lipidome components that perform vital biological functions. To facilitate the study of CLs in lipid mixtures without resorting to offline or online separations, we have developed a gas-phase approach employing ion/ion reactions to charge invert anionic lipid species using a trivalent metal-complex. Specifically, ytterbium(III) is shown to readily complex with three neutral ligands, N,N,N′,N′-tetra-2-ethylhexyl diglycolamide (TEHDGA), to form [Yb(TEHDGA 3 )] 3+ using ESI. Herein, we describe pilot studies to evaluate [Yb(TEHDGA) 3 ] 3+ as an ion/ion reagent to allow for chemical separation of doubly and singly charged anions, using lipid mixtures as examples, without neutralizing ions of either charge state.

Aza-Prilezhaev Aziridination-Enabled Multidimensional Analysis of Isomeric Lipids via High-Resolution U-Shaped Mobility Analyzer–Mass Spectrometry

“…Over the past decades, the field of lipidomics exponentially grew through the use of a variety of approaches. − Conventional tandem mass spectrometry (MS/MS) methods allow one to analyze the levels of lipid sum composition and the fatty acyl composition, but are blind to isomeric variants arising from different carbon–carbon bonding motifs. , Gas-phase ion activation methods including radical-directed dissociation (RDD), , ultraviolet photodissociation (UVPD), , ozone-induced dissociation (OzID), − electro impact excitation of ions from organic (EIEIO), , and oxygen attachment dissociation (OAD) , have been successfully employed in resolving isomeric lipids. However, taking membrane abundant glycerophospholipids (GP) as an example, annotations of five levels in terms of structure information (lipid class, the length and desaturation degree of fatty acyl, fatty acyl sn -positions, and the location and stereochemistry of CC in fatty acyl) remain a challenge in complex biological samples due to low physiological content, wide polarity range of different subclasses, and interference from excess saturated lipids.…”