Establishment of mass spectrometric fingerprints of novel synthetic cholesteryl neoglycolipids: The presence of a unique C-glycoside species during electrospray ionization and during collision-induced dissociation tandem mass spectrometry

Abstract

In this study we evaluated the fragmentation pattern of 16 novel amphiphilic neoglycolipid cholesteryl derivatives that can be efficiently used to increase cationic liposomal stability and to enhance gene transfer ability. These neoglycolipids bear different sugar moieties, such as D-glucosamine, In addition, we observed a unique ion that could not be rationally explained by the expected fragmentation of these amphiphilic molecules. The structure of this ion was tentatively proposed with that of a C-glycoside species formed by a chemical reaction between the sugar portion and the cholesterol. MS/MS analysis of this unique [C-glycoside] ϩ confirmed the validity of the proposed structure of this ion. The presence of an amino group at position C-2 and free hydroxyl groups of the sugar motif is crucial for the formation of a "reactive" sugar oxonium ion that can form the [C-glycoside] ϩ species. In summary, we precisely established the fragmentation patterns of the tested series of neoglycolipid cholesteryl derivatives and authenticated their structure as well; moreover, we speculated on the formation of a C-glycoside with the ESI source under atmospheric pressure and in the collision cell during MS/MS analysis. (J Am Soc Mass Spectrom 2007, 18, 294 -310)

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

“…Mass spectrometry combined with chromatographic techniques has become very popular owing to its sensitivity and selectivity [9]. The analysis of steroids has been carried out by gas chromatography-mass spectrometry (GC-MS) [10][11][12][13][14][15][16], liquid chromatography-mass spectrometry (LC-MS) [17][18][19], electrospray mass spectrometry (ESI-MS) [20][21][22][23][24], atmospheric pressure chemical ionization mass spectrometry (APCI-MS) [25], matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) [26][27][28], and immunoassay [29]. Although GC-MS approaches are highly sensitive, they have some limitations due to the need for multistep derivatization procedures for these thermally-labile compounds, especially those that contain large numbers of hydroxyl groups [9,30,31].…”

Tandem Mass Spectrometric Analysis of the Novel Gemini Surfactant Nanoparticle Families G12-s and G18:1-s

“…[33] For example, using electrospray ionization (ESI), the MS=MS analysis of 18 novel cholesteryl neoglycolipids, used in liposomes-based gene delivery, resulted in the formation of specific common fingerprint fragments regardless of the nature of the sugar moiety or the spacer group that linked the carbohydrate portion to the lipid cholesteryl moiety. [34] In addition, the unknown molecular structure of lipid A, isolated from the A. salmonicida lipopolysaccharide, was established by single-stage MS and MS=MS analysis using ESI ionization and quadrupole time-of-flight (Qq-ToF) MS=MS techniques. [35,36] Similarly, the fragmentation routes of morphine antagonists were precisely determined using ESI-Qq-ToF MS=MS.…”

The in situ gas‐phase formation of a C‐glycoside ion obtained during electrospray ionization tandem mass spectrometry. A unique intramolecular mechanism involving an ion‐molecule reaction

“…We have reported the electrospray ionization mass spectrometry (ESI‐MS) and low‐energy collision‐induced dissociation tandem mass spectrometry (CID‐MS/MS) of a series of synthetic neoglycolipids measured with a hybrid quadrupole‐quadrupole‐time‐of‐flight (QqTOF)‐MS instrument . The amphiphilic neoglycolipids were composed of a polar end consisting of a 2‐amino‐2‐deoxy‐ and 2‐acetamido‐2‐deoxy‐D‐glucoside linked to a polyethylene spacer which was covalently linked to a lipophilic cholesteryl moiety . We have also recently produced evidence for the in situ formation of a [C‐glycoside+H] + species, both at the electrospray interface and in the collision cell, during CID‐MS/MS measurements .…”

“…The understanding of this unique ' in situ ' gas‐phase C ‐glycosylation should provide novel insights into new synthetic routes for these compounds . To our knowledge, the gas‐phase formation of this [C‐glycoside+H] + ion has never been reported . It is important to mention that in recent decades the therapeutic values of the C ‐glycoside analogues have been established as anticancer vaccines, treatments for melanoma metastases, and protection against malaria …”

“…[7,8] The amphiphilic neoglycolipids were composed of a polar end consisting of a 2-amino-2-deoxy-and 2-acetamido-2deoxy-D-glucoside linked to a polyethylene spacer which was covalently linked to a lipophilic cholesteryl moiety. [7,8] We have also recently produced evidence for the in situ formation of a [C-glycoside+H] + species, both at the electrospray interface and in the collision cell, during CID-MS/MS measurements. [7,8] The gas-phase formation of this unique product ion was proposed incorrectly as an 'intermolecular' reaction occurring by an ion-molecule reaction, between the sugar oxonium and the neutral 3,5-cholestadiene molecule, both formed following the excision of the ethylene glycol spacer from the protonated neoglycolipid.…”