Electrospray ionization tandem mass spectral analysis of oxidation products of precursors of sulfur mustards

Electrospray ionization tandem mass spectral (ESI-MSn) analysis of thiodiglycol, bis(2-hydroxyethylthio)alkanes (BHETAs) and their mono-, di-, tri-, and tetraoxygenated compounds was carried out to obtain their characteristic spectra for ESI-MS analysis. These compounds are important markers of chemical warfare agents, namely sulfur mustards. ESI-MSn (n > or = 3) analysis of a compound by collisionally induced dissociation in an ion trap gives rise to mass spectra that are somewhat similar to electron ionization mass spectra. These ESI-MSn spectra can be used for compound identification. Under ESI-MS and ESI-MS/MS the compounds mostly produced [M+NH4]+, [M+H]+ and [M+H--H2O]+ ions. Fragmentations of these even-electron precursors in the ion trap gave rise to characteristic product ions via neutral loss of O2, H2O, C2H4, HCHO, C2H4O, C2H4S, HSC2H4OH and C2H4SO. Fragmentation routes of these compounds are proposed that rationalize the formation of product ions in ESI-MSn analysis.     

Electrospray ionisation tandem mass spectrometry of poly

Evaluation of polymer end-capping reactions with the aid of electrospray ionisation tandem mass spectrometry techniques (ESI-MS(n)) allows characterisation of novel poly[(R, S)-3-hydroxybutanoic acid]-(a-PHB) telechelics, containing primary hydroxyl groups at both polymer chain ends. The chemical structures of individual mass-selected macromolecules of the well-defined a-PHB telechelics have been defined in this way, and fragmentation mechanisms have been proposed. Copyright 1999 John Wiley & Sons, Ltd.     

Electrospray ionization mass spectral studies of N,N-dialkylaminoethane-2-sulphonic acids

Oxidative reactions of VX type compounds and N,N-dialkylaminoethane-2-thiols that are precursors for VX compounds produce N,N-dialkylaminoethane-2-sulphonic acids, N(R(1))(R(2))-CH(2)-CH(2)SO(3)H (where R(1) and R(2) = methyl, ethyl, n-propyl and isopropyl, 1-10), as the degradation products, and these degradation products are considered as markers for the detection of chemicals listed in the schedules of Chemical Weapons Convention (CWC) chemicals. Off-site detection of such degradation products in aqueous samples is an important task in the verification of CWC-related chemicals. Here we report a simple method involving the direct analysis of aqueous samples using positive and/or negative ion electrospray ionization (ESI) for the screening, detection and identification of N,N-dialkylaminoethane-2-sulphonic acids, avoiding sample preparation and chromatographic steps. The positive ion ESI mass spectra of all the compounds result in abundant [M+Na](+) ions, and the negative ion spectra show abundant [M-H](-) ions to confirm their molecular weight. The collision-induced dissociation spectra of [M+Na](+) and [M-H](-) give characteristic product ions by which it is easy to detect and identify all the studied N,N-dialkylaminoethane-2-sulphonic acids including those of isomeric compounds. The method is successfully applied to detect the spiked chemical, N,N-diisopropylaminoethane-2-sulphonic acid, present in a water sample received in a proficiency test.     

Electrospray ionisation tandem mass spectrometry in the characterisation of isomeric benzofurocoumarins

A set of aminoalkoxy-substituted, differently annullated furocoumarins, differing in the position of the aminoalkoxy chain and in the unsaturation level of the fused ring, has been subjected to electron impact and electrospray ionisation (ESI) experiments. In order to achieve a distinct characterisation of isomeric compounds, which partially failed under electron impact conditions, collision-induced dissociation experiments were performed on protonated molecules. The breakdown curves obtained by varying the tickle voltage on an ion trap ESI instrument led to the desired characterisation.     

Electrospray ionisation Fourier-transform ion cyclotron resonance mass spectrometry of dynamic combinatorial libraries

The use of electrospray ionisation Fourier-transform ion cyclotron resonance tandem mass spectrometry (ESI-FTICR-MS/MS) for the analysis of dynamic combinatorial libraries (DCLs) of pseudo-peptide macrocyclic hydrazone oligomers is presented. The design of library building blocks results in mixtures of compounds with greater diversity than libraries generated by conventional combinatorial chemistry and so presents increased demands for analysis. The extended capabilities of the FTICR technique, specifically selective ion trapping, sensitivity, high resolution and mass accuracy over a broad mass range, are compatible with these increased demands and, most importantly, without the need for chromatography. Preliminary studies on the sequencing of cyclic oligomers and confirmation of the presence of sequence isomers are presented. These studies highlight the potential of FTICR-MS as a superior technique for the analysis of combinatorially generated compounds.     

Electrospray ionisation mass spectrometric detection of weak non-covalent interactions in nogalamycin-DNA complexes

We demonstrate the use of electrospray ionisation mass spectrometry (ESI-MS) in high salt solutions for the analysis of weak non-covalent complexes of the anthracycline antibiotic nogalamycin with novel DNA hairpin structures; high signal-to-noise ratios for the complexes in the absence of bound Na+ ions permits relative binding affinities to be estimated.     

Electrospray ionisation tandem mass spectrometric study of hydrogen-bonding interactions of some disaccharides with lysine

The efficiency of formation of protonated heterotrimers of lysine with underivatised sugars (mono-, di-, and trisaccharides) and N-acetylglucosamine (N-AcGlc) was studied under electrospray ionisation conditions. The collision induced dissociation spectra of [Lys + sugar + NAcGlc + H](+) resulted in [Lys + NAcGlc + H](+) and [Lys + sugar + H](+) as the major product ions. Relative abundances of these two fragments reflect the extent of adduct formation of protonated lysine plus sugar, with reference to the reference compound NAcGlc. This relative abundance ratio was found to be characteristic of the sugar structure. In this way it was observed that the ability of lysine to form a protonated heterodimer with neutral sugars increases with an increase in the number of acetal oxygens. Lactose showed an anomalously high affinity for protonated Lys, possibly reflecting the axial hydroxyl at C4. The postulated involvement of the epsilon-NH(2) group of lysine in the formation of protonated heterodimers with sugars was supported by similar results of similar experiments with NH(3) in place of lysine.     

Electrospray ionisation tandem mass spectrometric investigation of phenylpropanoids and secoiridoids from solid olive residue

This work is focused on the recovery and structural characterisation of bioactive compounds from SOR (solid olive residue), a low cost and widely available by-product in the Mediterranean basin. In the light of the interesting biological activities attributed both to secoiridoid and phenylpropanoids, the aim of this work was to carry out a systematic tandem mass spectrometric study for the identification and characterisation of these two class of compounds extracted from SOR derived from Coratina, a cultivar widely diffused in the south of Italy. Five phenylpropanoids, in addition to verbascoside, and two new secoiridoids were identified.     

Electrospray ionization mass spectral 3nvestigations on multi-nuclear complexes of an azacryptand

The electrospray ionization (ES) mass spectrum of a trisodium azacryptate derived from a template reaction of sodium 2,6-diformyl-4-methylphenolate (sdmp) with 2,2′,2″-triaminoethylamine (tren) was investigated and compared with those by fast atom bombardment (FAB), atmospheric pressure chemical ionization (APCI) and electronic ionization (EI) methods. Dinuclear transition metal complexes of this hexaimine macrobicyclic ligand obtained by transmetallation were also studied by ES mass spectra. An [M₂L]⁺ species has been observed for divalent metal complexes, and an [MLH]⁺ species for a trivalent metal complex. The possible mechanism of the fragmentation process is discussed.     

Nucleophilic substitution by grignard reagents on sulfur mustards

With proper activation of the leaving group, sulfur mustards react with Grignard reagents with neighboring group participation of the sulfur atom. 2,6-Dichloro-9-thiabicyclo[3.3.1]nonane is especially useful in this regard, providing clean reactivity with organomagnesium nucleophiles on a topologically constrained scaffold.     

Electron ionisation mass spectral studies of bridgehead‐fused Δ2‐norbornanethiazolines

The electron ionisation (EI) mass spectra of a series of bridgehead‐fused Δ²‐norbornanethiazolines, a new class of bridgehead‐norbornane derivatives, have been studied and their cleavage mechanisms rationalised on the basis of the substituent shifts as well as on the identification of relevant peaks through accurate mass measurements and collision‐induced dissociation tandem mass spectrometric experiments. The fragmentation patterns of isomeric pairs of 6,6‐ and 10,10‐dimethylnorbornanethiazolines are almost identical, probably due to an initial isomerisation of molecular ion previous to the fragmentation. In general, the dominant peaks in the spectra of all the studied compounds originate from initial α‐cleavages of C(5)–C(6) or C(1)–C(10) bonds, followed by concomitant homolytic cleavage of C(1)–C(9) and C(7)–C(10) bonds. The driving force for this fragmentation pathway, directed by the gem‐dimethyl group, is the formation of a highly stabilised thiazolilmethyl cation which constitutes the base peak in all the spectra and allows the identification of these interesting ligands. Copyright © 2009 John Wiley & Sons, Ltd.     

Electrospray ionization mass spectrometric studies on the amphoteric surfactant cocamidopropylbetaine.

After liquid chromatographic (LC) separation, electrospray ionization mass spectrometry (ESI-MS) was investigated for the determination of the amphoteric surfactant cocamidopropylbetaine (CAPB). In the positive ion mode the molecule formed the adduct ions [M + H](+), [M + Na](+) and [M + K](+). Adducts of these cations were also detected with decreasing abundance as dimer and trimer clusters. Additionally, doubly charged molecular ions with different combinations of cations were identified. It was noticed that the relative abundances of individual cation adducts were not reproducible, apparently owing to varying contents of alkali metal ions originating from the solvent and the sample. Under negative ionization, the major molecular ion was [M - H](-). Higher clusters formed by two and three surfactant molecules, i.e. [2M - H](-) and [3M - H](-) were likewise registered. The tendency to form clusters in both positive and negative ion modes, even at 0.1 mg l(-1) levels, was attributed to strong electrostatic interactions between the zwitterionic head groups. Further evidence for this assumption was provided by the detection of a fragment formed from [2M - H](-) which contained the two charged head groups. Studies were undertaken in the negative ion mode on the concentration- and orifice voltage-dependent monomer, dimer and trimer formation of C(12)-CAPB in order to evaluate potential issues in using the ion [M - H](-) mode for quantitative analysis. Finally, the established (-)-LC/ESI-MS method was applied to follow up the primary degradation of CAPB in a laboratory-scale fixed-bed bioreactor (FBBR) spiked with a test concentration of 10 mg l(-1). Direct analysis without sample pretreatment revealed that higher alkyl homologues were more prone to adsorption. Primary biodegradation of all alkyl homologues was completed after a period of 4 days. Selected lyophilized FBBR samples were examined for the presence of transient or stable degradation intermediates, but no metabolite could be identified.     

Electrospray tandem mass spectrometric analysis of zeaxanthin and its oxidation products

Carotenoids have been implicated in protection of the eye from light-mediated photo-toxicity caused by free radicals. Under conditions of normal oxidative stress the carotenoids serve as protective antioxidants; however, when the oxidative stress exceeds the antioxidant capacity, carotenoids can be oxidized into numerous cleavage products. The determination and identification of oxidized carotenoids in biological samples remains a major challenge due to the small sample size and low stability of these compounds. We investigated the reaction of various zeaxanthin cleavage products with O-ethyl hydroxylamine to evaluate their levels in a biological sample. For this, a sensitive and specific electrospray tandem mass spectrometry (ESI-MS/MS) was developed, avoiding the classical lower sensitive and specific HPLC-UV and fluorescence absorption methods. Protonated molecules [M + H](+) of carotenoids upon collision-induced dissociation produced a number of structurally characteristic product ions. A series of complicated clusters of product ions differing in 14 (CH(2))and 26 (C(2)H(2))Da was characteristic of the polyene chain of intact carotenoids. All carotenoid ethyl oximes of zeaxanthin cleavage products were characterized by the losses of 60 and 61 Da in their MS/MS spectra. Through the application of the LC/MS/MS method, we identified two oxime derivatives of 3-hydroxy-beta-ionone and 3-hydroxy-14'-apocarotenal with protonated molecules at m/z 252 and m/z 370 respectively, in a human eye sample.     

Further mass spectral studies of flavones

Further evidence supporting the structure of the [M ? 1]⁺ ion found in the mass spectrum of flavone as being the [dibenzo-β-tropolone ? H]⁺ species was obtained by comparison of linked scan measurements performed in flavone, 3-deuteroflavone, 5,6,7,8-tetradeuteroflavone, 2′,3′,4′,5′,6′-pentadeuteroflavone and dibenzo-β-tropolone. This fragmentation process has also been demonstrated in the case of 3-methoxyflavone by high-resolution measurements, deuterium labelling, metastable decompositions and evaluation of the subspectra of 9-methoxyfluorenol, fluorenone and biphenylene. The structure of the ion at m/z 181 in the spectrum of flavone was found to be the [2-phenylbenzoxetane ? 1]⁺ species.     

Electrospray tandem mass spectrometric studies of phosphopeptides and phosphopeptide analogues

A set of synthetic phosphopeptides and phosphopeptide analogues was studied by tandem nano-electrospray mass spectrometry. The influence of the collision offset and of the charge state of the molecular ion on phosphate-specific fragmentation processes was investigated in detail. H--D exchange experiments and structural considerations support a six-centered transition being present in the neutral loss of H3PO4 from serine, threonine and homoserine phosphopeptides, where the C-alpha hydrogen of serine or threonine or the C-beta hydrogen of homoserine is transferred to the protonated phosphate group. Neutral loss of H3PO4 at moderate collision offset potential represents a very abundant fragmentation process for serine, threonine and homoserine phosphopeptides. The most specific feature for discrimination of these phosphopeptides from tyrosine phosphopeptides is the m/z 79:97 ratio in the negative ion product spectra, which is consistently elevated in tyrosine phosphopeptides as compared with serine, threonine and homoserine phosphopeptides. The fragment ions of methylphosphono- and H-phosphonopeptides can be explained by the same mechanisms as are applicable to phosphopeptides.     

Electrospray mass spectrometry studies of macromolecules containing 1,3-oxazolidine moieties

The polycondensation of terephthalaldehyde with 2-amino-2-methyl-1,3-propanediol using acidic catalysts leads to the formation of linear polymers and macrocyclic compounds with 2-(1',4'-phenylene)-5-methyl-1-aza-3,7-dioxabicyclo[3.3.0]octane as the repeating unit in all compounds. The structure of the polymer was determined by 1H- and 13C-NMR spectroscopy, and electrospray ionization mass spectrometric (ESI-MS) analysis. ESI-MS measurements were used to study the details of the polymer structure and support the equimolar alternating nature of bicyclo-O,N-acetals of terephthaldehyde in these macromolecules. Copyright