Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) allows detailed characterization of complex petroleum samples at the level of elemental composition assignment. ...Ultrahigh-resolution (450 000−650 000 at m/z 500) enables identification of isobaric species that differ in mass by 3 mDa or less, and high mass accuracy (mass error of better than 300 ppb), combined with Kendrick mass sorting, allows for unambiguous molecular formula assignment to each of more than 10 000−20 000 peaks in each mass spectrum. Thus, it is possible to identify, sort, and monitor thousands of elemental compositions simultaneously, as a function of the boiling point. Here, the detailed FT-ICR MS characterization of an Athabasca bitumen heavy vacuum gas oil (HVGO) distillation series exposes the progression of heteroatom class, type (double bond equivalents (DBE), number of rings plus double bonds to carbon), and carbon number for tens of thousands of crude oil species, as a function of the boiling point. Specifically, we analyze a distillation series of Athabasca bitumen HVGO with cut temperatures from the initial boiling point (IBP) to 538 °C (in eight cuts) by atmospheric pressure photoionization (APPI), as well as positive and negative electrospray ionization (ESI) FT-ICR MS, to determine the distributions of nonpolar and polar species, as a function of the HVGO boiling point. Compositional distributions reveal definitive heteroatom class, type, and carbon number trends among distillation cuts, and provide the first detailed compositional evidence in support of the Boduszynski model that describes the progression of petroleum composition and structure as a function of the boiling point. Quantitation of the aromaticity and carbon number profiles of both polar and nonpolar species in all distillate cuts further affirms the validity of the Boduszynski model for the HVGO distillate range, and provides evidence for cycloalkane linkages, in addition to polyaromatic cores.
High-resolution mass spectrometers Marshall, Alan G; Hendrickson, Christopher L
Annual review of analytical chemistry (Palo Alto, Calif.),
01/2008, Letnik:
1
Journal Article
Recenzirano
Over the past decade, mass spectrometry has been revolutionized by access to instruments of increasingly high mass-resolving power. For small molecules up to approximately 400 Da (e.g., drugs, ...metabolites, and various natural organic mixtures ranging from foods to petroleum), it is possible to determine elemental compositions (C(c)H(h)N(n)O(o)S(s)P(p)...) of thousands of chemical components simultaneously from accurate mass measurements (the same can be done up to 1000 Da if additional information is included). At higher mass, it becomes possible to identify proteins (including posttranslational modifications) from proteolytic peptides, as well as lipids, glycoconjugates, and other biological components. At even higher mass ( approximately 100,000 Da or higher), it is possible to characterize posttranslational modifications of intact proteins and to map the binding surfaces of large biomolecule complexes. Here we review the principles and techniques of the highest-resolution analytical mass spectrometers (time-of-flight and Fourier transform ion cyclotron resonance and orbitrap mass analyzers) and describe some representative high-resolution applications.
With the rapid growth of therapeutic monoclonal antibodies (mAbs), stringent quality control is needed to ensure clinical safety and efficacy. Monoclonal antibody primary sequence and ...post-translational modifications (PTM) are conventionally analyzed with labor-intensive, bottom-up tandem mass spectrometry (MS/MS), which is limited by incomplete peptide sequence coverage and introduction of artifacts during the lengthy analysis procedure. Here, we describe top-down and middle-down approaches with the advantages of fast sample preparation with minimal artifacts, ultrahigh mass accuracy, and extensive residue cleavages by use of 21 tesla FT-ICR MS/MS. The ultrahigh mass accuracy yields an RMS error of 0.2–0.4 ppm for antibody light chain, heavy chain, heavy chain Fc/2, and Fd subunits. The corresponding sequence coverages are 81%, 38%, 72%, and 65% with MS/MS RMS error ~4 ppm. Extension to a monoclonal antibody in human serum as a monoclonal gammopathy model yielded 53% sequence coverage from two nano-LC MS/MS runs. A blind analysis of five therapeutic monoclonal antibodies at clinically relevant concentrations in human serum resulted in correct identification of all five antibodies. Nano-LC 21 T FT-ICR MS/MS provides nonpareil mass resolution, mass accuracy, and sequence coverage for mAbs, and sets a benchmark for MS/MS analysis of multiple mAbs in serum. This is the first time that extensive cleavages for both variable and constant regions have been achieved for mAbs in a human serum background.
Graphical Abstract
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The compositional analysis (speciation) of heavy oil products is a key step to improve our understanding of hydrotreatment processes and reaction mechanisms. Thus, detailed characterization of polar ...fractions, such as asphaltenes, should be considered. Here, we employ atmospheric pressure photoionization Fourier transform ion cyclotron mass spectrometry to monitor the evolution of the asphaltene hydrocarbon and sulfur families in deep hydrotreatment processes (fixed and ebullated beds). The results suggest that the complexity of the asphaltenic fractions (in terms of chemical polydispersity) is drastically lowered with increased process severity. In either fixed or ebullated beds, the evolution of the sulfur species is quite similar in class composition, aromaticity (DBE/carbon number ratio), and polycondensation (DBE). The compositional changes are marked by a drastic increase in aromaticity to highly polycondensed dealkylated aromatic structures. Asphaltene disaggregation followed by a dealkylation of the remaining species could be suggested. The proposed scheme would converge toward those previously proposed.
Carbonaceous presolar grains of supernovae origin have long been isolated and are determined to be the carrier of anomalous ²²Ne in ancient meteorites. That exotic ²²Ne is, in fact, the decay isotope ...of relatively short-lived ²²Na formed by explosive nucleosynthesis, and therefore, a selective and rapid Na physical trapping mechanism must take place during carbon condensation in supernova ejecta. Elucidation of the processes that trap Na and produce large carbon molecules should yield insight into carbon stardust enrichment and formation. Herein, we demonstrate that Na effectively nucleates formation of Na@C ₆₀ and other metallofullerenes during carbon condensation under highly energetic conditions in oxygen- and hydrogen-rich environments. Thus, fundamental carbon chemistry that leads to trapping of Na is revealed, and should be directly applicable to gas-phase chemistry involving stellar environments, such as supernova ejecta. The results indicate that, in addition to empty fullerenes, metallofullerenes should be constituents of stellar/circumstellar and interstellar space. In addition, gas-phase reactions of fullerenes with polycyclic aromatic hydrocarbons are investigated to probe “build-up” and formation of carbon stardust, and provide insight into fullerene astrochemistry.
We have coupled atmospheric pressure photoionization (APPI) to a home-built 9.4-T Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. Analysis of naphtho2,3-apyrene and crude oil ...mass spectra reveals that protonated molecules, deprotonated molecules, and radical molecular ions are formed simultaneously in the ion source, thereby complicating the spectra (>12 000 peaks per mass spectrum and up to 63 peaks of the same nominal mass), and eliminating the “nitrogen rule” for nominal mass determination of number of nitrogens. Nevertheless, the ultrahigh mass resolving power and mass accuracy of FT-ICR MS enable definitive elemental composition assignments, even for doublets as closely spaced as 1.1 mDa (SH3 13C vs 12C4). APPI efficiently ionizes nonpolar compounds that are unobservable by electrospray and allows nonpolar sulfur speciation of petrochemical mixtures.
An understanding of chemical formation mechanisms is essential to achieve effective yields and targeted products. One of the most challenging endeavors is synthesis of molecular nanocarbon. ...Endohedral metallofullerenes are of particular interest because of their unique properties that offer promise in a variety of applications. Nevertheless, the mechanism of formation from metal-doped graphite has largely eluded experimental study, because harsh synthetic methods are required to obtain them. Here we report bottom-up formation of mono-metallofullerenes under core synthesis conditions. Charge transfer is a principal factor that guides formation, discovered by study of metallofullerene formation with virtually all available elements of the periodic table. These results could enable production strategies that overcome long-standing problems that hinder current and future applications of metallofullerenes.
Most gastrointestinal stromal tumors (GISTs) exhibit aberrant activation of the receptor tyrosine kinase (RTK) KIT. The efficacy of the inhibitors imatinib mesylate and sunitinib malate in GIST ...patients has been linked to their inhibition of these mutant KIT proteins. However, patients on imatinib can acquire secondary KIT mutations that render the protein insensitive to the inhibitor. Sunitinib has shown efficacy against certain imatinib-resistant mutants, although a subset that resides in the activation loop, including D816H/V, remains resistant. Biochemical and structural studies were undertaken to determine the molecular basis of sunitinib resistance. Our results show that sunitinib targets the autoinhibited conformation of WT KIT and that the D816H mutant undergoes a shift in conformational equilibrium toward the active state. These findings provide a structural and enzymologic explanation for the resistance profile observed with the KIT inhibitors. Prospectively, they have implications for understanding oncogenic kinase mutants and for circumventing drug resistance.
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