Monoisotopic Mass?

The current IUPAC-recommended definition of the term "monoisotopic mass" of a chemical species is based on the most abundant isotopes of the constituent elements. It has even been proposed to constrain the definition to be based only on the atomic masses of the most abundant stable isotopes. Such an approach is flawed because in this way several elements and their compounds, in addition to isotopically enriched species, would not merit to be assigned a monoisotopic mass. Furthermore, for large molecules, such as proteins, the monoisotopic mass as currently defined loses its significance. Therefore, we propose to eliminate using the current definition altogether. Instead, the term isotopologue mass should be applied uniformly to every species denoted by a specific chemical formula.

Helium-Plasma-Ionization Mass Spectrometry of Metallocenes and Their Derivatives.

Ferrocene and its derivatives and nickelocene undergo facile ionization when exposed directly to the ionizing plasma of a helium-plasma ionization (HePI) source. Mass spectra recorded from such samples under ambient positive-ion-generating conditions show intense peaks for the respective molecular ions [M+•] and protonated species [(M + H)+]. The protonation process occurs most efficiently when traces of water are present in the heated nitrogen used as the "heating gas." In fact, the relative population of the two categories of ions generated in this way can be manipulated by regulating the heating-gas flow. Moreover, rapid and highly efficient gas-phase hydrogen-deuterium exchange (HDX) reactions can be performed in the ion source by passing the heating gas through a vial with D2O before it reaches the HePI source. Moreover, the ionized species generated in this way can be subjected to in-source CID fragmentation in the QDa-HePI source very efficiently by varying the sampling-cone voltage. By this procedure, ions generated from ferrocene and nickelocene could be stripped so far as to ultimately generate the bare-metal cation. Other typical fragment-ions produced from protonated metallocenes included the M(cp)1+ ions (M = Fe or Ni), by elimination of a cyclopentadiene molecule, or the molecular cation, by loss of a H• radical. Moreover, H/D exchanges and subsequent tandem mass spectrometric analysis indicated that the central metal core participates in the initial protonation process of ferrocene under HePI conditions. However, in compounds such as ferrocene carboxaldehyde and ferrocene boronic acid, the protonation takes place at the peripheral functional group.

HCN emission by a Polydesmid Millipede Detected Remotely by Reactive Adsorption on Gold Nanoparticles Followed by Laser Desorption/Ionization Mass Spectrometry (LDI-MS).

Hydrocyanic acid (HCN) is a well-known defensive allomone in the chemical arsenal of millipedes in the order Polydesmida. The presence of HCN in the headspace vapor of adult Xystocheir dissecta (Wood, 1867), a common millipede from the San Francisco Bay Area, was traced by laser desorption/ionization-mass spectrometry (LDI-MS). To accomplish this, the headspace vapor surrounding caged, live millipedes was allowed to diffuse passively over gold-nanoparticle (AuNP) deposits placed at various distances from the emitting source. The stainless steel plates with AuNP deposits were removed and irradiated by a 355-nm laser. The gaseous ions generated in this way were detected by time-of-flight mass spectrometry. The intensity of the mass spectrometric peak detected at m/z 249 for the Au(CN)2- complex anion was compared to that of the residual Au- signal (m/z 197). Using this procedure, HCN vapors produced by the live millipedes could be detected up to 50 cm away from the source. Furthermore, the addition of H2O2, as an internal oxygen source for the gold cyanidation reaction that takes place in the AuNP deposits, significantly increased the detection sensitivity. Using the modified H2O2 addition procedure, HCN could now be detected at 80 cm from the source. Moreover, we found a decreasing intensity ratio of the Au(CN)2-/Au- signals as the distance from the emitting source increased, following an exponential-decay distribution as predicted by Fick's law of diffusion. Graphical abstract.

1,4-Benzoquinone as a Highly Efficient Dopant for Enhanced Ionization and Detection of Nitramine Explosives on a Single-Quadrupole Mass Spectrometer Fitted with a Helium-Plasma Ionization (HePI) Source.

Previous investigations have evaluated the efficacy of anions such as NO3-, Cl-, Br-, CH3COO-, and CF3COO- as additives to generate or enhance mass spectrometric signals from explosives under plasma ionization conditions. The results of this study demonstrate that for detecting nitramine-class explosives, such as 1,3,5-trinitroperhydro-1,3,5-triazine (RDX) and 1,3,5,7-tetranitro-1,3,5,7-tetrazacyclooctane (HMX), 1,4-benzoquinone (BQ) is a highly effective and efficient dopant. When used in conjunction with ambient-pressure negative-ion helium-plasma ionization (HePI), 1,4-benzoquinone readily captures an electron, forming an abundant molecular anion (m/z 108), which upon exposure to vapors of RDX and HMX generates adduct ions of m/z 330 and 404, respectively. The signal level recorded for RDX upon adduction to the radical anion of 1,4-benzoquinone under our experimental conditions was significantly higher than that realized by chloride adduction using dichloromethane (DCM) as the dopant.

Fortuitous Ion-Molecule Reaction Enables Enumeration of Metal-Hydrogen Bonds Present in Gaseous Ions.

Upon mass selection and ion activation under mass spectrometric conditions, gaseous formate adducts of many metal formates undergo decarboxylation and form product ions that bear metal-hydrogen bonds. Fortuitously, we noted that negative-ion spectra of several such formate adducts showed many peaks that could not be rationalized by the conventional fragmentation pathways attributed to the precursor ion. Subsequent experimentation proved that these enigmatic peaks are due to an ion-molecule reaction that takes place between traces of adventitious water vapor in the collision gas and the in situ formed product anions bearing metal-hydrogen bonds, generated by the fragmentation of the formate adducts. Results show that metal-hydrogen bonds of the group 2 elements are particularly susceptible to this reaction. For example, in the product-ion spectrum of [Sr(η2-O2CH)3]-, the peak at m/z 91 for SrH3 - was accompanied by three peaks at higher m/z ratios. These peaks, at m/z 107, 123, and 139, represented SrH2(OH)1 -, SrH1(OH)2 -, and Sr(OH)3 -, respectively. These satellite peaks, which were separated by 16 m/z units, were attributed to adducts formed due to the high affinity of gas-phase anions bearing metal-hydrogen bonds to water. Although undesired, these peaks are diagnostically useful to determine the number of metal-hydrogen bonds present in a precursor ion. Even though the peaks were less pronounced, analogous reactions were noted from the adducts of the group 1 elements as well. Moreover, Gibbs free energy values computed for the interaction of [H-Mg(η2-O2CH)2]- with water to form [HO-Mg(η2-OCOH)2]- and H2 indicated that this is an exergonic reaction.

Gold Nanoparticles (AuNPs) as Reactive Matrix for Detection of Trace Levels of HCN in Air by Laser Desorption/Ionization Mass Spectrometry (LDI-MS).

Under direct laser desorption/ionization mass spectrometric conditions, the irradiation of target spots made of gold nanoparticle residues generates a series of peaks at m/z 197, 394, 591… representing Aun- ions (n = 1-3). In contrast, spectra recorded from gold nanoparticles directly mixed with an alkali cyanide exhibited an additional peak at m/z 249, indicating an abundant generation of gaseous [Au(CN)2]- ions upon irradiation. The relative intensity of the m/z 249 peak surged when the amount of cyanide in the mixture was increased. Most remarkably, a peak at m/z 249 was observed even from neat AuNPs upon irradiation, if a nearby spot, which was not irradiated, happened to bear a cyanide sample. We postulated that traces of HCN emanating from the headspace of aqueous cyanide solution during the sample-plate preparation is sufficient to convert gold to AuCN, which is subsequently detected as [Au(CN)2]-. Further experiments demonstrated that the relative intensity of the m/z 249 peak diminishes exponentially as the AuNP spot becomes more distant from the putative HCN source. Eventually, the method was developed as an efficient procedure to detect HCN or alkali cyanides. Using KCN, the detection limits were determined to be below 10 pg of CN- per spot. The method also demonstrated that, upon crushing, the seeds or roots of certain fruits and vegetables such as apple, peach, radish, and cassava, but not carrot, release HCN in amounts detectable by this method. Graphical Abstract.

Brimstone chemistry under laser light assists mass spectrometric detection and imaging the distribution of arsenic in minerals.

Singly charged As2n+1 ion clusters (n = 2-11) were generated from elemental arsenic by negative-ion laser-ablation mass spectrometry. The overall abundance of the gaseous As ions generated upon laser irradiation was enhanced nearly a hundred times when As-bearing samples were admixed with sulfur. However, sulfur does not act purely as an inert matrix: irradiating arsenic-sulfur mixtures revealed a novel pathway to generate and detect a series of [AsSn]- clusters (n = 2-6). Intriguingly, the spectra recorded from As2O3, NaAsO2, Na3AsO4, cacodylic acid and 3-amino-4-hydroxyphenylarsonic acid together with sulfur as the matrix were remarkably similar to that acquired from an elemental arsenic and sulfur mixture. This result indicated that arsenic sulfide cluster-ions are generated directly from arsenic compounds by a hitherto unknown pathway. The mechanism of elemental sulfur extracting chemically bound arsenic from compounds and forming [AsSn]- clusters is enigmatic; however, this discovery has a practical value as a general detection method for arsenic compounds. For example, the method was employed for the detection of As in its minerals, and for the imaging of arsenic distribution in minerals such as domeykite. LDI-MS data recorded from a latent image imprinted on a piece of paper from a flat mineral surface, and wetting the paper with a solution of sulfur, enabled the localization of arsenic in the mineral. The distribution of As was visualized as false-color images by extracting from acquired data the relative intensities of m/z 139 (AsS2-) and m/z 171 (AsS3-) ions.

Periodic Trends Manifested through Gas-Phase Generation of Anions Such as [AlH4]-, [GaH4]-, [InH4]-, [SrH3]-, [BaH3]-, [Ba(0)(η2-O2CH)1]-, [Pb(0)H]-, [Bi(I)H2]-, and Bi- from Formates.

Metal-hydride anions of main group elements, such as BaH3 - and InH4 -, were generated by dissociating formate adducts of the respective metal formates. Upon activation, these adducts fragment by formate-ion ejection or by decarboxylation. For adducts of alkali-metal formates, the formate-ion ejection is the preferred pathway, whereas for those of alkaline-earth and group 13-15 metals, the expulsion of CO2 is the more favorable pathway. Decarboxylation is deemed to yield a metal-hydrogen bond presumably by a hydride transfer to the metal atom. For example, the decarboxylation of Al(η-OCOH)4 - and Ga(η-OCOH)4 - generated AlH4 - and GaH4 -, respectively. The initial fragment-ion with a H-M bond formed in this way from adducts of the heavier metals of group 13 (Ga, In, and Tl) undergo a unimolecular reductive elimination, ascribable to the "inert-pair" effect, to lower the metal-ion oxidation state from +3 to +1. As group 13 is descended, the tendency for this reductive elimination process increases. PbH3 -, generated from the formate adduct of lead formate, reductively eliminated H2 to form PbH-, in which Pb is in oxidation state zero. In the energy-minimized structure [H-Pb(η2-H2)]-, proposed as an intermediate for the process, a H2 molecule is coordinated with PbH- as a dihapto ligand. The formate adducts of strontium and barium produce monoleptic ions such as [M(0)(η2-O2CH)1]-, in which the formate ion is chelated to a neutral metal atom. The bismuth formate adduct undergoes a double reductive elimination process whereby the oxidation state of Bi is reduced from +3 to +1 and then to -1. Upon activation, the initially formed [H-Bi-H]- ion transforms to an anionic η2-H2 complex, which eliminates dihydrogen to form the bismuthide anion (Bi-).

Influence of Ionization Source Conditions on the Gas-Phase Protomer Distribution of Anilinium and Related Cations.

The gas-phase-ion generation technique and specific ion-source settings of a mass spectrometer influence heavily the protonation processes of molecules and the abundance ratio of the generated protomers. Hitherto that has been attributed primarily to the nature of the solvent and the pH. By utilizing electrospray ionization and ion-mobility mass spectrometry (IM-MS), we demonstrate, even in the seemingly trivial case of protonated aniline, that the protomer ratio strongly depends on the source conditions. Under low in-source ion activation, nearly 100% of the N-protomer of aniline is produced, and it can be subsequently converted to the C-protomer by collisional activation effected by increasing the electrical potential difference between the entrance and exit orifices of the first vacuum region. This activation and transformation process takes place even before the ion is mass-selected and subjected to IM separation. Despite the apparent simplicity of the problem, the preferred protonation site of aniline in the gas phase-the amino group or the aromatic ring-has been a topic of controversy. Our results not only provide unambiguous evidence that ring- and nitrogen-protonated aniline can coexist and be interconverted in the gas phase, but also that the ratio of the protomers depends on the internal energy of the original ion. There are many dynamic ion-transformation and fragmentation processes that take place in the different physical compartments of a Synapt G2 HDMS instrument. Such processes can dramatically change the very identity even of small ions, and therefore should be taken into account when interpreting product-ion mass spectra. Graphical Abstract ᅟ.

Nominal Mass?

The current IUPAC-recommended definition of the term "nominal mass," based on the most abundant naturally occurring stable isotope of an element, is flawed. We propose that Nominal mass should be defined as the sum of integer masses of protons and neutrons in any chemical species. In this way, all isotopes and isotopologues can be assigned a definitive identifier. Graphical Abstract ᅟ.

Collision-induced dissociation processes of protonated benzoic acid and related compounds: competitive generation of protonated carbon dioxide or protonated benzene.

Upon activation in the gas phase, protonated benzoic acid (m/z 123) undergoes fragmentation by several mechanisms. In addition to the predictable water loss followed by a CO loss, the m/z 123 ion more intriguingly eliminates a molecule of benzene to generate protonated carbon dioxide (H - O+ ═ C ≡ O, m/z 45), or a molecule of carbon dioxide to yield protonated benzene (m/z 79). Experimental evidence shows that the incipient proton ambulates during the fragmentation processes. For the CO2 or benzene loss, protonated benzoic acid transfers the charge-imparting proton initially to the ortho position and then to the ipso position to generate a transient species which dissociates to form an ion-neutral complex between benzene and protonated CO2 . The formation of the m/z 45 ion is not a phenomenon unique to benzoic acid: spectra from protonated isophthalic acid, terephthalic acid, trans-cinnamic acid and some aliphatic acids also displayed a peak for m/z 45. However, the m/z 45 peak is structurally diagnostic only for certain benzene polycarboxylic acids because the spectra of compounds with two carboxyl groups on adjacent ring carbons do not produce a peak at m/z 45. For the m/z 79 ion to be formed, an intramolecular reaction should take place in which protonated CO2 within the ion-neutral complex acts as the attacking electrophile to transfer a proton to benzene. Copyright © 2017 John Wiley & Sons, Ltd.

Oxidative Ionization Under Certain Negative-Ion Mass Spectrometric Conditions.

1,4-Hydroquinone and several other phenolic compounds generate (M - 2) -• radical-anions, rather than deprotonated molecules, under certain negative-ion mass spectrometric conditions. In fact, spectra generated under helium-plasma ionization (HePI) conditions from 1,4-hydroquinone and 1,4-benzoquinone (by electron capture) were practically indistinguishable. Because this process involves a net loss of H• and H+, it can be termed oxidative ionization. The superoxide radical-anion (O2-•), known to be present in many atmospheric-pressure plasma ion sources operated in the negative mode, plays a critical role in the oxidative ionization process. The presence of a small peak at m/z 142 in the spectrum of 1,4-hydroquinone, but not in that of 1,4-benzoquinone, indicated that the initial step in the oxidative ionization process is the formation of an O2-• adduct. On the other hand, under bona fide electrospray ionization (ESI) conditions, 1,4-hydroquinone generates predominantly an (M - 1) - ion. It is known that at sufficiently high capillary voltages, corona discharges begin to occur even in an ESI source. At lower ESI capillary voltages, deprotonation predominates; as the capillary voltage is raised, the abundance of O2-• present in the plasma increases, and the source in turn increasingly behaves as a composite ESI/APCI source. While maintaining post-ionization ion activation to a minimum (to prevent fragmentation), and monitoring the relative intensities of the m/z 109 (due to deprotonation) and 108 (oxidative ionization) peaks recorded from 1,4-hydroquinone, a semiquantitative estimation of the APCI contribution to the overall ion-generation process can be obtained. Graphical Abstract ᅟ.

Competitive homolytic and heterolytic decomposition pathways of gas-phase negative ions generated from aminobenzoate esters.

An alkyl-radical loss and an alkene loss are two competitive fragmentation pathways that deprotonated aminobenzoate esters undergo upon activation under mass spectrometric conditions. For the meta and para isomers, the alkyl-radical loss by a homolytic cleavage of the alkyl-oxygen bond of the ester moiety is the predominant fragmentation pathway, while the contribution from the alkene elimination by a heterolytic pathway is less significant. In contrast, owing to a pronounced charge-mediated ortho effect, the alkene loss becomes the predominant pathway for the ortho isomers of ethyl and higher esters. Results from isotope-labeled compounds confirmed that the alkene loss proceeds by a specific γ-hydrogen transfer mechanism that resembles the McLafferty rearrangement for radical cations. Even for the para compounds, if the alkoxide moiety bears structural motifs required for the elimination of a more stable alkene molecule, the heterolytic pathway becomes the predominant pathway. For example, in the spectrum of deprotonated 2-phenylethyl 4-aminobenzoate, m/z 136 peak is the base peak because the alkene eliminated is styrene. Owing to the fact that all deprotonated aminobenzoate esters, irrespective of the size of the alkoxy group, upon activation fragment to form an m/z 135 ion, aminobenzoate esters in mixtures can be quantified by precursor ion discovery mass spectrometric experiments.

Regulated In Situ Generation of Molecular Ions or Protonated Molecules under Atmospheric-Pressure Helium-Plasma-Ionization Mass Spectrometric Conditions.

In an enclosed atmospheric-pressure helium-plasma ionization (HePI) source engulfed with dehumidified ambient gases, molecular cations are generated from compounds such as toluene, bromobenzene, and iodobenzene. Evidently, the ionization is effected by a direct Penning mechanism attributable to interactions of the gas-phase analyte with metastable helium atoms. It is widely known that secondary ions generated from ambient gases also play an important role in the overall ionization process. For example, when the ambient gases bear even traces of moisture, the analytes are ionized by proton transfer reactions with gaseous H3O(+). In this study, we demonstrate how a controlled variation of experimental conditions can manipulate the abundance of molecular ions and protonated molecules in a HePI source.

Real-time monitoring of in situ gas-phase H/D exchange reactions of cations by atmospheric pressure helium plasma ionization mass spectrometry (HePI-MS).

An enclosed atmospheric-pressure helium-plasma ionization (HePI-MS) source avoids, or minimizes, undesired back-exchange reactions usually encountered during deuterium incorporation experiments under ambient-pressure open-source conditions. A simple adaptation of an ESI source provides an economical way of conducting gas phase hydrogen/deuterium (H/D) exchange reactions (HDX) in real time without the need for complicated hardware modifications. For example, the spectrum of [(2)H8]toluene recorded under exposed ambient conditions showed the base peak at m/z 96 due to fast leaching of ring hydrogens because of interactions with H2O vapor present in the open source. Such D/H exchanges are rapidly reversed if the deuterium-depleted [(2)H8]toluene is exposed to D2O vapor. In addition to the enumeration of labile protons, our procedure enables the identification of protonation sites in molecules unambiguously, by the number of H/D exchanges observed in real time. For example, molecules such as tetrahydrofuran and pyridine protonate at the heteroatom and consequently undergo only one H/D exchange, whereas ethylbenzene, which protonates at a ring position of the aromatic ring, undergoes six H/D exchanges. In addition, carbocations generated in situ by in-source fragmentation of precursor protonated species, such as benzyl alcohol, do not undergo any rapid H/D exchanges. Because radical cations, second-generation cations (ions formed by losing a small molecule from a precursor ion), or those formed by hydride abstraction do not undergo rapid H/D exchanges, our technique provides a way to distinguish these ions from protonated molecules.

Direct detection of solid inorganic mercury salts at ambient pressure by electron-capture and reaction-assisted HePI mass spectrometry.

Solid HgCl2 is readily detected at ambient conditions by electron capture in a HePI-MS source. The captured electron occupies the empty 6 s orbital of the Hg atom. The resulting radical-anion HgCl2 (-•) can exist as three "flexomers" of different Cl-Hg-Cl angle. The facile in-source formation of HgCl2 (-•) and the adduct [HgCl3](--) is exploited to detect other solid Hg compounds by exposing them to an external chloride source, such as HCl, NaCl, or vapors emanating from solid TiCl3. In situ oxidation of Hg2Cl2 with H2O2 generated signals for HgCl2 (-•) and [HgCl3] (-), suggesting that oxidation makes Hg 6 s orbital available for electron capture.

Direct detection and identification of active pharmaceutical ingredients in intact tablets by helium plasma ionization (HePI) mass spectrometry.

A simple modification converts an electrospray ion source to an ambient-pressure helium plasma ionization source without the need of additional expensive hardware. Peaks for active ingredients were observed in the spectra recorded from intact pharmaceutical tablets placed in this source. A flow of heated nitrogen was used to thermally desorb analytes to gas phase. The desorption temperatures were sometimes as low as 50 °C. For example, negative-ion spectra recorded from an aspirin tablet showed peaks at m/z 137 (salicylate anion) and 179 (acetylsalicylate anion) which were absent in the background spectra. The overall ion intensity increased as the desorption gas temperature was elevated. Within the same acquisition experiment, both positive- and negative-ion signals for acetaminophen were recorded from volatiles emanating from Tylenol tablets by switching the polarity of the capillary back and forth. Moreover, different preparations of acetaminophen tablets could be distinguished by their ion-intensity thermograms.

Direct detection and identification of active pharmaceutical ingredients in intact tablets by helium plasma ionization (HePI) mass spectrometry / 药物分析学报

A simple modification converts an electrospray ion source to an ambient-pressure helium plasma ionization source without the need of additional expensive hardware. Peaks for active ingredients were observed in the spectra recorded from intact pharmaceutical tablets placed in this source. A flow of heated nitrogen was used to thermally desorb analytes to gas phase. The desorption temperatures were sometimes as low as 50 1C. For example, negative-ion spectra recorded from an aspirin tablet showed peaks at m/z 137 (salicylate anion) and 179 (acetylsalicylate anion) which were absent in the background spectra. The overall ion intensity increased as the desorption gas temperature was elevated. Within the same acquisition experiment, both positive- and negative-ion signals for acetaminophen were recorded from volatiles emanating from Tylenol tablets by switching the polarity of the capillary back and forth. Moreover, different preparations of acetaminophen tablets could be distinguished by their ion-intensity thermograms.

Enhancement of laser desorption ionization mass spectrometric signals of cesium iodide by elemental sulfur.

RATIONALE: The utility of elemental sulfur as a matrix for inorganic salts such as CsI, AgI, and KI was investigated because the conventional matrices deployed to generate gaseous ions from organic compounds, upon irradiation with a laser beam, are not suitable for inorganic salts. METHODS: Sulfur and inorganic salts were admixed and irradiated with a 337-nm UV laser. Laser desorption ionization (LDI) mass spectra were recorded in both positive and negative ion mode on a time-of-flight mass spectrometer. RESULTS: The positive ion laser desorption ionization mass spectrum of CsI showed peaks at m/z 133, 393, etc. for [(CsI)(n)Cs](+) ions. Similarly, negative ion spectra showed peaks at m/z 387, 647, etc. for [(CsI)(n)I](-) ions. However, for n >2 ion clusters, the intensities of peaks were negligibly small in both ionization modes. In contrast, spectra recorded from CsI admixed with elemental sulfur showed peaks up to n = 13 for (CsI)(n)Cs(+), and n = 9 for (CsI)(n)I(-). A similar enhancement of ion abundances by sulfur was observed for the cluster ions generated from KI and AgI. CONCLUSIONS: The dramatic increase in intensities of the higher-mass CsI cluster peaks suggests that sulfur acts as a laser-absorbing matrix for inorganic salts far superior to conventional matrices such as 2,5-dihydroxybenzoic acid and α-cyano-4-hydroxycinnamic acid.