Explore the vast range of titles available.

Each different molecular elemental composition--e.g., CcHhNnOoSs--has a different exact mass. With sufficiently high mass resolving power (m/Δm₅₀% [almost equal to] 400,000, in which m is molecular mass and Δm₅₀% is the mass spectral peak width at half-maximum peak height) and mass accuracy (<300 ppb) up to [almost equal to]800 Da, now routinely available from high-field (greater-than-or-equal9.4 T) Fourier transform ion cyclotron resonance mass spectrometry, it is possible to resolve and identify uniquely and simultaneously each of the thousands of elemental compositions from the most complex natural organic mixtures, including petroleum crude oil. It is thus possible to separate and sort petroleum components according to their heteroatom class (NnOoSs), double bond equivalents (DBE = number of rings plus double bonds involving carbon, because each ring or double bond results in a loss of two hydrogen atoms), and carbon number. \"Petroleomics\" is the characterization of petroleum at the molecular level. From sufficiently complete characterization of the organic composition of petroleum and its products, it should be possible to correlate (and ultimately predict) their properties and behavior. Examples include molecular mass distribution, distillation profile, characterization of specific fractions without prior extraction or wet chemical separation from the original bulk material, biodegradation, maturity, water solubility (and oil:water emulsion behavior), deposits in oil wells and refineries, efficiency and specificity of catalytic hydroprocessing, \"heavy ends\" (asphaltenes) analysis, corrosion, etc.

We describe the design and initial performance of the first 21 tesla Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer. The 21 tesla magnet is the highest field superconducting magnet ever used for FT-ICR and features high spatial homogeneity, high temporal stability, and negligible liquid helium consumption. The instrument includes a commercial dual linear quadrupole trap front end that features high sensitivity, precise control of trapped ion number, and collisional and electron transfer dissociation. A third linear quadrupole trap offers high ion capacity and ejection efficiency, and rf quadrupole ion injection optics deliver ions to a novel dynamically harmonized ICR cell. Mass resolving power of 150,000 ( m/Δm 50% ) is achieved for bovine serum albumin (66 kDa) for a 0.38 s detection period, and greater than 2,000,000 resolving power is achieved for a 12 s detection period. Externally calibrated broadband mass measurement accuracy is typically less than 150 ppb rms, with resolving power greater than 300,000 at m/z 400 for a 0.76 s detection period. Combined analysis of electron transfer and collisional dissociation spectra results in 68% sequence coverage for carbonic anhydrase. The instrument is part of the NSF High-Field FT-ICR User Facility and is available free of charge to qualified users. Graphical Abstract ᅟ

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.

Tremendous advances in nanoscience have been made since the discovery of the fullerenes; however, the formation of these carbon-caged nanomaterials still remains a mystery. Here we reveal that fullerenes self-assemble through a closed network growth mechanism by incorporation of atomic carbon and C 2 . The growth processes have been elucidated through experiments that probe direct growth of fullerenes upon exposure to carbon vapour, analysed by state-of-the-art Fourier transform ion cyclotron resonance mass spectrometry. Our results shed new light on the fundamental processes that govern self-assembly of carbon networks, and the processes that we reveal in this study of fullerene growth are likely be involved in the formation of other carbon nanostructures from carbon vapour, such as nanotubes and graphene. Further, the results should be of importance for illuminating astrophysical processes near carbon stars or supernovae that result in C 60 formation throughout the Universe. The formation mechanisms of fullerenes remain unclear. This study shows that fullerenes self-assemble through a closed network growth mechanism in which atomic carbon and C 2 are incorporated into the growing closed cages.

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 ᅟ

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. An understanding of the formation mechanism of endohedral metallofullerenes may pave the way towards targeted synthesis of these nanomaterials. Here, the authors investigate their bottom-up synthesis and determine that charge transfer plays a key role in their formation.

We tested a long-standing hypothesis within river ecology, predicted by the River Continuum Concept, that dissolved organic matter (DOM) diversity decreases with stream order. We measured DOM molecular composition across three stream orders in the headwaters of well characterized forested catchments with ultrahigh-resolution mass spectrometry to assess DOM chemogeography and chemodiversity over the spatial scales of climatic regions and fluvial networks. Stream waters with similar dissolved organic carbon (DOC) concentrations in different climatic regions had distinctive DOM compositions, but shared 69.5 % of the 3286 individual chemical formulae detected. DOM compositions common to all watersheds were characterized by abundant lignin-like and tannin-like molecules as well as carboxyl-rich alicyclic-like molecules (CRAM); 50 % of all formulae were found in all streams. Of the roughly 700 unique chemical formulae within a given fluvial network, most were outside the CRAM region within a van Krevelen diagram and 78 to 95 % were restricted to 1st-order streams where diffuse ground water sources surface, coalesce into a channel, and flow downstream. The 1st-order streams within a fluvial network also exhibited the highest formula diversity as well as the greatest numbers of formulae across a broad range of compound classes.

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.

An ultimate goal in carbon nanoscience is to decipher formation mechanisms of highly ordered systems. Here, we disclose chemical processes that result in formation of high-symmetry clusterfullerenes, which attract interest for use in applications that span biomedicine to molecular electronics. The conversion of doped graphite into a C 80 cage is shown to occur through bottom-up self-assembly reactions. Unlike conventional forms of fullerene, the iconic Buckminsterfullerene cage, I h -C 60 , is entirely avoided in the bottom-up formation mechanism to afford synthesis of group 3-based metallic nitride clusterfullerenes. The effects of structural motifs and cluster–cage interactions on formation of compounds in the solvent-extractable C 70 –C 100 region are determined by in situ studies of defined clusterfullerenes under typical synthetic conditions. This work establishes the molecular origin and mechanism that underlie formation of unique carbon cage materials, which may be used as a benchmark to guide future nanocarbon explorations. An understanding of how caged carbon materials self-assemble from doped graphite is a long-standing challenge. Here, the authors show that distinct bottom-up processes lead to the synthesis of high-symmetry clusterfullerenes.

Aminoacyl-tRNA synthetases-interacting multifunctional protein3 (AIMP3/p18) is involved in the macromolecular tRNA synthetase complex via its interaction with several aminoacyl-tRNA synthetases. Recent reports reveal a novel function of AIMP3 as a tumor suppressor by accelerating cellular senescence and causing defects in nuclear morphology. AIMP3 specifically mediates degradation of mature Lamin A (LmnA), a major component of the nuclear envelope matrix; however, the mechanism of how AIMP3 interacts with LmnA is unclear. Here we report solution-phase hydrogen/deuterium exchange (HDX) for AIMP3, LmnA, and AIMP3 in association with the LmnA C-terminus. Reversed-phase LC coupled with LTQ 14.5 T Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) results in high mass accuracy and resolving power for comparing the D-uptake profiles for AIMP3, LmnA, and their complex. The results show that the AIMP3-LmnA interaction involves one of the two putative binding sites and an adjacent novel interface on AIMP3. LmnA binds AIMP3 via its extreme C-terminus. Together these findings provide a structural insight for understanding the interaction between AIMP3 and LmnA in AIMP3 degradation.