High-resolution Electrospray Mass Spectrometry Research Articles

Identification of a new tert-leucinate class synthetic cannabinoid in powder and “spice-like” herbal incenses: Methyl 2-[[1-(5-fluoropentyl)indole-3-carbonyl]amino]-3,3-dimethyl-butanoate (5F-MDMB-PICA)

A brown powder and different product packages of “spice-like” herbal incenses were analyzed using a systematic identification approach based on liquid chromatography with diode array detector (HPLC-PDA) and gas chromatography mass spectrometry (GC–MS) with computer based library search against spectral libraries. However, the most predominant compound in the methanolic sample solutions could not be identified. In order to elucidate the chemical structure, a more extensive analysis of the material was initiated using liquid chromatography mass spectrometry (LC–MS), electrospray high resolution mass spectrometry (ESI-HRMS) and 1H, 13C and 19F nuclear magnetic resonance spectroscopy (NMR), which allowed the identification and characterization of the major compound as methyl 2-[[1-(5-fluoropentyl)indole-3-carbonyl]amino]-3,3-dimethyl-butanoate (5F-MDMB-PICA).The goal of this study is to provide analytical information for the identification of this new tert-leucinate class synthetic cannabinoid by various analytical methods.

Anion-templated nanosized silver clusters protected by mixed thiolate and diphosphine.

S2-, MoO42-, and Mo6O228- were successfully employed as templates in the formation of six high-symmetry polynuclear silver clusters as exemplified in the single-crystal X-ray structures of [S@Ag18(tBuC6H4S)16(dppp)4]·DMF·5CH3CN·3CH3OH (1), [MoO4@Ag24(MeC6H4S)12(dppm)6(MoO4)4]·2BF4·C2H5NO (2), [MoO4@Ag24(MeC6H4S)12(dppm)6(MoO4)4]·2CF3SO3 (3), [MoO4@Ag24(MeC6H4S)12(dppf)6(MoO4)4]·2CF3SO3 (4), [MoO4@Ag24(MeC6H4S)12(dppb)6(MoO4)4]·2CF3SO3 (5) and [Mo6O22@Ag46(tBuC6H4S)32(dppm)4(CH3CN)8]·6CF3SO3 (6) (dppp = 1,3-bis(diphenylphosphino)propane, dppm = bis(diphenylphosphino)methane, dppf = 1,1'-bis(diphenylphosphino)ferrocene and dppb = 1,4-bis(diphenylphosphino)butane). Cluster 1 is a S2--centered octadecanuclear banana-shaped molecule. Clusters 2-5 have similar structures consisting of a tetrahedron of a MoO42- core and four MoO42- where three silver atoms cap each face and a pair sits on each edge, giving tetraicosanuclear ball-shaped molecules. Although different diphosphine ligands and silver salts were used in the syntheses, 2-5 contain a common building cluster unit with similar geometry and nuclearity. With (Bu4N)2Mo6O19 as a template, a giant 46-silver-atom cluster encapsulates an in situ modified Mo6O228- unit. The nuclearity and geometry depend on the size and shape of the templates. High-resolution electrospray mass spectrometry (HR-ESI-MS) analyses of 4 indicate its exceptionally high stability in acetonitrile. The solid-state luminescence of 1 as a function of the temperature exhibits thermochromism from red to yellow due to the different intensities of the two bands. This work established a new strategy for the construction of polynuclear silver clusters using an anionic template and mixed S- and P-donor ligands where a promising approach for building novel dual emissive materials is unraveled.

Self-assembled supramolecular cages containing dinuclear ruthenium(II) polypyridyl complexes

Four dinuclear ruthenium(II) terpyridine complexes containing terminal pyridyl groups were synthesised for assembly into larger heterometallic supramolecular structures. These 4nm long metalloligands are capable of binding additional metal ions. Combination of tetrakis(acetonitrile)palladium(II) tetrafluoroborate with one of the dinuclear complexes lead to rapid self-assembly of a [Pd2L4]20+ cage, which was characterised using high resolution electrospray mass spectrometry and NMR spectroscopy, including diffusion measurements.

Dual reductive/oxidative electrochemistry/liquid chromatography/mass spectrometry: Towards peptide and protein modification, separation and identification

A new hyphenated technique based on on-line dual (oxidative and reductive) electrochemistry coupled to liquid chromatography and high resolution electrospray mass spectrometry is presented. Two liquid streams are combined, with one containing a disulfide, which is reduced to the respective thiol in an electrochemical cell based on a titanium working electrode. The other stream contains phenol, which is electrochemically activated to benzoquinone on a boron-doped diamond working electrode. Upon combination of the two streams, a Michael addition takes places, leading to the covalent coupling of thiol to quinone. In continuous flow, the reaction mixture is transferred into an injection valve and the products are separated by reversed phase liquid chromatography and detected by electrospray-high resolution mass spectrometry. Proof of concept is demonstrated for low molecular mass disulfides and peptides, but further optimization will be required in future work to achieve efficient protein labelling.

Orthogonal Synthesis of "Easy-to-Read" Information-Containing Polymers Using Phosphoramidite and Radical Coupling Steps.

A new orthogonal solid-phase iterative strategy is proposed for the synthesis of sequence-coded polymers. This approach relies on the use of two successive chemoselective steps: (i) phosphoramidite coupling, and (ii) radical-radical coupling. These repeated steps can be performed using two different types of building blocks, i.e. a phosphoramidite monomer that also contains an alkyl bromide and a hydroxy-functionalized nitroxide. The phosphoramidite and the hydroxy group are reacted in step (i), thus leading to a phosphite that is oxidized in situ into a phosphate bond. The alkyl bromide is activated by copper bromide in step (ii) to afford a carbon-centered radical that is spin-trapped in situ by the nitroxide. The iterative repetition of these steps allow synthesis of uniform polymers, as evidenced by high-resolution electrospray mass spectrometry. Moreover, binary information could be easily implemented in the polymers using different types of phosphoramidite monomers in step (i). Interestingly, it was found that the formed information-containing polymers are very easy to sequence by tandem mass spectrometry due to the presence of easily cleavable alkoxyamine bonds formed in step (ii).

Investigating the Transformations of Polyoxoanions Using Mass Spectrometry and Molecular Dynamics.

The reactions of [γ-SiW10O36]8– represent one of the most important synthetic gateways into a vast array of polyoxotungstate chemistry. Herein, we set about exploring the transformation of the lacunary polyoxoanion [β2-SiW11O39]8– into [γ-SiW10O36]8– using high-resolution electrospray mass spectrometry, density functional theory, and molecular dynamics. We show that the reaction proceeds through an unexpected {SiW9} precursor capable of undertaking a direct β → γ isomerization via a rotational transformation. The remarkably low-energy transition state of this transformation could be identified through theoretical calculations. Moreover, we explore the significant role of the countercations for the first time in such studies. This combination of experimental and the theoretical studies can now be used to understand the complex chemical transformations of oxoanions, leading to the design of reactivity by structural control.

Inventory of metal complexes circulating in plant fluids: a reliable method based on HPLC coupled with dual elemental and high-resolution molecular mass spectrometric detection.

Description of metal species in plant fluids such as xylem, phloem or related saps remains a complex challenge usually addressed either by liquid chromatography-mass spectrometry, X-ray analysis or computational prediction. To date, none of these techniques has achieved a complete and true picture of metal-containing species in plant fluids, especially for the least concentrated complexes. Here, we present a generic analytical methodology for a large-scale (>10 metals, >50 metal complexes) detection, identification and semiquantitative determination of metal complexes in the xylem and embryo sac liquid of the green pea, Pisum sativum. The procedure is based on direct injection using hydrophilic interaction chromatography with dual detection by elemental (inductively coupled plasma mass spectrometry) and molecular (high-resolution electrospray mass spectrometry) mass spectrometric detection. Numerous and novel complexes of iron(II), iron(III), copper(II), zinc, manganese, cobalt(II), cobalt(III), magnesium, calcium, nickel and molybdenum(IV) with several ligands including nicotianamine, citrate, malate, histidine, glutamine, aspartic acid, asparagine, phenylalanine and others are observed in pea fluids and discussed. This methodology provides a large inventory of various types of metal complexes, which is a significant asset for future biochemical and genetic studies into metal transport/homeostasis.

Analysis and fragmentation mechanisms of hirsutinolide-type sesquiterpene lactones by ultra-high-performance liquid chromatography/electrospray ionization linear ion trap Orbitrap mass spectrometry.

Hirsutinolide-type sesquiterpene lactones (SLs) are natural biologically active compounds mainly found in the genus Vernonia. Very few studies have been published about the fragmentation mechanisms of SLs generally and none about hirsutinolides, although they have drawn attention through their biological and taxonomical interest. This work aims to propose a mass spectrometry fragmentation pattern for hirsutinolides in order to detect and to identify them in a botanical extract. The fragmentation pathways of six pure hirsutinolides isolated from Pseudelephantopus spiralis were established by positive ion electrospray high-resolution linear ion trap Orbitrap tandem mass spectrometry (ESI(+)-HRMS(n) ). A resolutive, hyphenated ultra-high-performance liquid chromatography (UHPLC) coupled to diode array detection (DAD) and ESI(+)-HRMS(n) method was then implemented to separate and analyze them. The ionization behaviour and diagnostic product ions were investigated by both methods. The UHPLC/DAD-ESI-HRMS(n) method was applied for the dereplication of a plant extract. For the six standard compounds, the main fragmentation pattern consists first in the loss of the side chain in the C-8 position followed by the loss of the substituent in the C-13 position. UHPLC/HRMS analyses of hirsutinolides mainly produced sodiated molecules or [M+H-H2 O](+) ions. The high-abundance product ions at m/z 299 and 259 were established to be the characteristic diagnostic ions of the hirsutinolide core. The analysis of a P. spiralis extract further led to the identification of two putative hirsutinolides. The UHPLC/DAD-HRMS(n) method combining characteristic fragmentation patterns and the profiles of the product ions generated in the MS and MS/MS spectra is an effective technique for characterizing hirsutinolide-type SLs.

Angelocunhol: New Erythroxylane Diterpene and Other Compounds fromSimira sampaioana(Rubiaceae)

The first Simira sampaioana (Rubiaceae) phytochemical study allowed the isolation and structural determination of a new erythroxylane diterpene named Angelocunhol, 11β,12α-dihydroxy-2,4(18),15-eritroxilatrien-1-one, together with 14 known compounds: simirane B, harman, maxonine, isomalindine, malindine, sitost-4-en-6-ol-3-one, estigmast-4,22-dien-6-ol-3-one, campest-4-en-6-ol-3-one, sitost-4-en-3-one, stigmast-4,22-dien-3-one, campest-4-en-3-one, β-sitosterol, stigmasterol, and stigmast-4,22-dien-3-ol from the wood of a specimen of the species. The structures of these compounds were elucidated on the spectroscopic-data analysis basis, mainly 1H and 13C nuclear magnetic resonance (NMR), including 2D experiments (1H-1H correlation spectroscopy (COSY), nuclear Overhauser spectroscopy (NOESY), heteronuclear multiple-bond correlation-HMBC and heteronuclear single-quantum correlation-HSQC), and high-resolution electrospray mass spectrometry (HRESI-MS).

The evaluation of matrix effects in pesticide multi-residue methods via matrix fingerprinting using liquid chromatography electrospray high-resolution mass spectrometry

Matrix fingerprinting of twenty-three different commodities was evaluated.

Spectroscopic Analyses on Reaction Intermediates Formed during Chlorination of Alkanes with NaOCl Catalyzed by a Nickel Complex

The spectroscopic, electrochemical, and crystallographic characterization of [((Me,H)PyTACN)Ni(II)(CH3CN)2](OTf)2 (1) ((Me,H)PyTACN = 1-(2-pyridylmethyl)-4,7-dimethyl-1,4,7-triazacyclononane, OTf = CF3SO3) is described together with its reactivity with NaOCl. 1 catalyzes the chlorination of alkanes with NaOCl, producing only a trace amount of oxygenated byproducts. The reaction was monitored spectroscopically and by high resolution electrospray-mass spectrometry (ESI-MS) with the aim to elucidate mechanistic aspects. NaOCl reacts with 1 in acetonitrile to form the transient species [(L)Ni(II)-OCl(S)](+) (A) (L = (Me,H)PyTACN, S = solvent), which was identified by ESI-MS. UV/vis absorption, electron paramagnetic resonance, and resonance Raman spectroscopy indicate that intermediate A decays to the complex [(L)Ni(III)-OH(S)](2+) (B) presumably through homolytic cleavage of the O-Cl bond, which liberates a Cl(•) atom. Hydrolysis of acetonitrile to acetic acid under the applied conditions results in the formation of [(L)Ni(III)-OOCCH3(S)](2+) (C), which undergoes subsequent reduction to [(L)Ni(II)-OOCCH3(S)](2+) (D), presumably via reaction with OCl(-) or ClO2(-). Subsequent addition of NaOCl to [(L)Ni(II)-OOCCH3(S)](+) (D) regenerates [(L)Ni(III)-OH(S)](2+) (B) to a much greater extent and at a faster rate. Addition of acids such as acetic and triflic acid enhances the rate and extent of formation of [(L)Ni(III)-OH(S)](2+) (B) from 1, suggesting that O-Cl homolytic cleavage is accelerated by protonation. Overall, these reactions generate Cl(•) atoms and ClO2 in a catalytic cycle where the nickel center alternates between Ni(II) and Ni(III). Chlorine atoms in turn react with the C-H bonds of alkanes, forming alkyl radicals that are trapped by Cl(•) to form alkyl chlorides.

Antimicrobial Properties of Mono- and Di-fac-rhenium Tricarbonyl 2-Pyridyl-1,2,3-triazole Complexes

A family of mono- and di-fac-rhenium tricarbonyl 2-pyridyl-1,2,3-triazole complexes with different aliphatic and aromatic substituents was synthesized in good-to-excellent yields (46–99 %). The complexes were characterized by 1H and 13C NMR spectroscopy, infrared spectroscopy, electronic (UV-visible) spectroscopy, high-resolution electrospray mass spectrometry, and elemental analyses. In four examples, the solid-state structures of the rhenium(i) complexes were confirmed by X-ray crystallography. The family of the mono- and di-rhenium(i) complexes and the corresponding 2-pyridyl-1,2,3-triazole was tested for antimicrobial activity in vitro against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) microorganisms. Agar-based disk diffusion assays indicated that most of the rhenium(i) complexes were active against Staphylococcus aureus and that the cationic rhenium(i) complexes were more active than the related neutral systems. However, in all cases, the minimum inhibitory concentrations for all the complexes were modest (i.e. 16–1024 µg mL–1).

New glycosylated biscoumarins from Hymenaea coubaril L. seeds

Hymenaea coubaril L. seeds are widely used by the population for the treatment of several ailments. Despite its popular use, no other phytochemical studies had been carried out about “Jatobá” seeds. For this reason, this is the first study on the matter and it was carried out with the purpose of finding and identifying the molecules that constitute this seed. This work presented the isolation and elucidation of two new biscoumarins from H. coubaril L. seeds. The new compounds: hymenain 7-O-β-glucopyranosyl-(1′′′→2′′)-O-α-apiofuranosyl-(1′′′′→2′′′)-O-α-galactopyranoside (1) and hymenain 7-O-β-glucopyranosyl-(1′′′→2′′)-O-α-apiofuranoside (2). Their structures were elucidated by extensive 1D and 2D NMR experiments, IR and electrospray high resolution mass spectrometry (ESI-HRMS).

Antifungal Molecules Produced by a New Salt-Tolerant and Alkaliphilic Streptomyces sp. BS30 Isolated from an Arid Soil

A salt-tolerant and alkaliphilic actinomycete BS30 isolated from a Saharan soil sample of Algeria, exhibited optimum growth at 2 % (w/v) NaCl and pH10. The strain exhibited antimicrobial activity against yeast and toxinogenic fungi. Analysis of the 16S rRNA gene sequence (1476 nucleotides) of the BS30 strain showed 98.77 % similarity with 16S rRNA gene sequence of Streptomyces spiroverticillatus NBRC 12821T, the most closely related type species. The phylogenetic analysis indicated that the BS30 strain represent a distinct phyletic line suggesting a potential new genomic species. Two bioactive molecules were isolated from the culture broth using various separation and purification steps. The first partially purified bioactive product was subjected to gas chromatography–mass spectrometry (GC–MS). The second fraction was analyzed by ultraviolet–visible (UV–VIS) spectrometry, electro-spray ionization mass (ESI–MS) and high resolution mass spectrometry (HR-ESI–MS) coupled with analytical liquid chromatography (HPLC) with a diode array detector (DAD). The two compounds showed significant antifungal activity against Aspergillus niger 2CA936.

Thiols in brewed coffee: Assessment by fast derivatization and liquid chromatography–high resolution mass spectrometry

In the present paper, we present a simple, reliable, selective and sensitive method for the identification and quantification of volatile thiols at trace levels in coffee brews. A simultaneous derivatization/extraction procedure followed by liquid chromatography–electrospray high-resolution mass spectrometry is proposed and adapted to coffee brew matrix, and the performance of the method is evaluated. The linearity, sensitivity, recovery and both the intra-day and inter-day accuracy were all satisfactory. According to established identification criteria, seven target and nine non-target thiols were identified and quantified in coffee brew samples. Several of them are reported here for the first time in coffee brews, and our results are in agreement with previously reported results for coffee powder analyzed using similar analytical approach.

An integrated strategy for rapid and accurate determination of free and cell-bound microcystins and related peptides in natural blooms by liquid chromatography–electrospray-high resolution mass spectrometry and matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry using both positive and negative ionization modes

An integrated high resolution mass spectrometry (HRMS) strategy has been developed for rapid and accurate determination of free and cell-bound microcystins (MCs) and related peptides in water blooms. The natural samples (water and algae) were filtered for independent analysis of aqueous and sestonic fractions. These fractions were analyzed by MALDI-TOF/TOF-MS and ESI-Orbitrap-HCD-MS. MALDI, ESI and the study of fragmentation sequences have been provided crucial structural information. The potential of combined positive and negative ionization modes, full scan and fragmentation acquisition modes (TOF/TOF and HCD) by HRMS and high resolution and accurate mass was investigated in order to allow unequivocal determination of MCs. Besides, a reliable quantitation has been possible by HRMS. This composition helped to decrease the probability of false positives and negatives, as alternative to commonly used LC–ESI-MS/MS methods. The analysis was non-target, therefore covered the possibility to analyze all MC analogs concurrently without any pre-selection of target MC. Furthermore, archived data was subjected to retrospective “post-targeted” analysis and a screening of other potential toxins and related peptides as anabaenopeptins in the samples was done. Finally, the MS protocol and identification tools suggested were applied to the analysis of characteristic water blooms from Spanish reservoirs.

Cation Exchange in Small ZnS and CdS Molecular Analogues

The simplest means of altering the chemistry and electronic structure of any material, from molecular clusters to single crystals, is by the introduction of chemical impurities. We present a systematic study of the cation exchange reaction involving Co(2+) ions with metal benzenethiolate clusters, [M4(SPh)10](2-) (M = Zn, Cd), yielding diluted magnetic clusters having the general formula [(M1-xCox)4(SPh)10](2-). This method allows high concentrations of doping at the molecular level without forming concentrated magnetic clusters such as [Co4(SPh)10](2-). Changes in the electronic structure of the molecular species containing on average <1 Co(2+) per cluster were observed and characterized by a variety of analytical (high-resolution electrospray mass spectrometry) and spectroscopic techniques (electronic absorption including stopped-flow kinetics, luminescence, and paramagnetic (1)H NMR). The mass spectrometry results strongly suggest that the cation exchange reaction with Co(2+) is thermodynamically favored for the [Zn4(SPh)10](2-) cluster compared to the [Cd4(SPh)10](2-) clusters at room temperature. The rate of the cation exchange is orders of magnitude faster for the [Cd4(SPh)10](2-) cluster than for [Zn4(SPh)10](2-) and is governed by ligand interconversion processes. This simple room temperature cation exchange into molecular clusters is a model reaction that provides important structural information regarding the effect of Co(2+) doping on the cluster stability.

Transformation of Au144(SCH2CH2Ph)60 to Au133(SPh-tBu)52 Nanomolecules: Theoretical and Experimental Study.

Ultrastable gold nanomolecule Au144(SCH2CH2Ph)60 upon etching with excess tert-butylbenzenethiol undergoes a core-size conversion and compositional change to form an entirely new core of Au133(SPh-tBu)52. This conversion was studied using high-resolution electrospray mass spectrometry which shows that the core size conversion is initiated after 22 ligand exchanges, suggesting a relatively high stability of the Au144(SCH2CH2Ph)38(SPh-tBu)22 intermediate. The Au144 → Au133 core size conversion is surprisingly different from the Au144 → Au99 core conversion reported in the case of thiophenol, -SPh. Theoretical analysis and ab initio molecular dynamics simulations show that rigid p-tBu groups play a crucial role by reducing the cluster structural freedom, and protecting the cluster from adsorption of exogenous and reactive species, thus rationalizing the kinetic factors that stabilize the Au133 core size. This 144-atom to 133-atom nanomolecule's compositional change is reflected in optical spectroscopy and electrochemistry.

Silver (I) as DNA glue: Ag(+)-mediated guanine pairing revealed by removing Watson-Crick constraints.

Metal ion interactions with DNA have far-reaching implications in biochemistry and DNA nanotechnology. Ag+ is uniquely interesting because it binds exclusively to the bases rather than the backbone of DNA, without the toxicity of Hg2+. In contrast to prior studies of Ag+ incorporation into double-stranded DNA, we remove the constraints of Watson-Crick pairing by focusing on homo-base DNA oligomers of the canonical bases. High resolution electro-spray ionization mass spectrometry reveals an unanticipated Ag+-mediated pairing of guanine homo-base strands, with higher stability than canonical guanine-cytosine pairing. By exploring unrestricted binding geometries, quantum chemical calculations find that Ag+ bridges between non-canonical sites on guanine bases. Circular dichroism spectroscopy shows that the Ag+-mediated structuring of guanine homobase strands persists to at least 90 °C under conditions for which canonical guanine-cytosine duplexes melt below 20 °C. These findings are promising for DNA nanotechnology and metal-ion based biomedical science.

Can Radiolysis Help Understanding the Decomposition Products of the Electrolytes Used in Lithium-Ion Batteries?

Lithium-ion batteries appear to be one of the most important advances in energy storage. Unfortunately, their performance declines gradually with their use and/or time. Nevertheless, their degradation products affect both the battery performance and its safety. Therefore it is of paramount importance to understand the reaction mechanisms involved in the ageing processes. Among those, redox processes are likely to play a critical role and radiolysis is an interesting approach in order to simulate the ageing phenomena. One of the aims of our group is then to investigate the effect of ionizing radiation on the different solvents containing or not lithium salts used in batteries. We generate, thus, the decomposition products that are actually comparable to those formed by electrolysis. Moreover, the use of the “radiolysis approach” entails particularly two important benefits: the time needed to degrade the solvent is much shorter than in classical charge/discharge cycles and it offers the possibility to explore different time scales processes (from picoseconds to days). Our work was first focused on linear alkyl carbonates diethyl and dimethyl carbonate (DEC and DMC) with/without LiPF6. At short-time scale, picosecond pulse radiolysis has been used in order to explore the primary radiation effects. These experiments reveal, for instance, an unambiguous reaction between the electron and the PF6 - anion. Then, the long-time decomposition products were analyzed both in the gas and liquid phase. To this end, a wide variety of analytical techniques has been used. Gas phase has been analyzed and quantified using Gas Chromatography-Electron Impact-Mass spectrometry (GC-EI-MS) whereas a combination of Electrospray-High Resolution Mass Spectrometry (ESI-HRMS) with both Ion Mobility Spectroscopy (IMS) and Infrared Multi-Photon Dissociation (IRMPD) spectroscopy has been used to characterize the decomposition products in the liquid phase. In conclusion, we show that the “radiolysis approach” used herein can provide an unprecedented, quantitative and fast overview of the electrolyte decomposition phenomenon.