Ion Mobility Spectrometry-Mass Spectrometry Coupled with Gas-Phase Hydrogen/Deuterium Exchange for Metabolomics Analyses

Ion mobility spectrometry-mass spectrometry (IMS-MS) in combination with gas-phase hydrogen/deuterium exchange (HDX) and collision-induced dissociation (CID) is evaluated as an analytical method for small-molecule standard and mixture characterization. Experiments show that compound ions exhibit unique HDX reactivities that can be used to distinguish different species. Additionally, it is shown that gas-phase HDX kinetics can be exploited to provide even further distinguishing capabilities by using different partial pressures of reagent gas. The relative HDX reactivity of a wide variety of molecules is discussed in light of the various molecular structures. Additionally, hydrogen accessibility scoring (HAS) and HDX kinetics modeling of candidate (in silico) ion structures is utilized to estimate the relative ion conformer populations giving rise to specific HDX behavior. These data interpretation methods are discussed with a focus on developing predictive tools for HDX behavior. Finally, an example is provided in which ion mobility information is supplemented with HDX reactivity data to aid identification efforts of compounds in a metabolite extract.

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The Ugi reaction with CF3-carbonyl compounds: effective synthesis of α-trifluoromethyl amino acid derivatives

The Ugi reaction with CF₃-carbonyl compounds is described in detail. The method is efficient for the multicomponent preparation of α-trifluoromethyl (Tfm) amino acids, α-Tfm containing dipeptides, and iminodicarboxylic acids. In addition, the first protected CF₃-opine derivative was prepared. The scope, limitations, and stereochemistry of the approach are discussed.     

Two modifications formed by "sulflower" C16S8 molecules, their study by XRD and optical spectroscopy (Raman, IR, UV-Vis) methods

Sublimation of sulflower, octathio[8]circulene C 16S 8 ( 1), on heating under high vacuum ( approximately 10 (-5) Torr) leads to successive formation of two modifications: a white film ( 1W) and a red polycrystalline solid ( 1R). When kept at room temperature for several weeks, 1W spontaneously turns pink, reflecting the monotropic phase transition 1W --> 1R. The accurate molecular and crystal structure of 1R has been studied using low-temperature (100 K) high-resolution single crystal X-ray analysis. The C 16S 8 molecule in crystal is strictly planar with nearly equalized bonds of each type (C-C, C-S, and CC). The point symmetry group of the free molecule is D 8 h , and the crystal space group is P2 1/ n. These data allowed group-theoretical analysis of vibrational normal modes to be accomplished. Investigation of the charge density distribution of 1R including Bader's AIM approach has revealed rather strong intermolecular S...S, S...C, and C...C interactions of charge transfer and pi-stacking types with overall lattice energy of 28.5 kcal/mol. The charge transfer due to the S...S interactions is the reason for the red coloration of 1R. The latter is reflected by its UV-vis spectrum exhibiting absorption bands in the visible region which are absent from that of 1W. Both modifications were studied comparatively by vibrational (Raman, IR) and electronic spectroscopies as well as XRD powder diffraction. All the results obtained are fully consistent and show that 1W is much less ordered than 1R with significantly weakened intermolecular interactions. Rationalizing of these results has led to an idea that 1W could be soluble, in contrast to 1R. Indeed, 1W appeared soluble in common solvents; this finding opens the way to the study of the chemistry of 1 and investigation of its electrooptical properties.     

Dependence of the quality of adhesion between poly(dimethylsiloxane) and glass surfaces on the conditions of treatment with oxygen plasma

Treatment with oxygen-containing plasma is an essential step for the fabrication of devices containing components of polydimethylsiloxane (PDMS). Such oxidative treatment chemically modifies the surface of PDMS allowing it to permanently adhere to glass, quartz, PDMS and other silica-based substrates. Overexposure of PDMS to oxidative gas plasma, however, compromises its adhesiveness. Therefore, regulation of the duration and the conditions of the plasma treatment is crucial for achieving sufficient surface activation without overoxidation. Using a semiquantitative ternary approach, we evaluated the quality of adhesion ( QA) between flat PDMS and glass substrates pretreated with oxygen plasma under a range of different conditions. The quality of adhesion manifested good correlation trends with the surface properties of the pretreated PDMS. Examination of the QA dependence on the treatment duration and on the pressure and the RF power of the plasma revealed a range of oxidative conditions that allowed for permanent adhesion with quantitative yields.     

Which Metals are Green for Catalysis? Comparison of the Toxicities of Ni,Cu, Fe,Pd, Pt,Rh, and Au Salts

Environmental profiles for the selected metals were compiled on the basis of available data on their biological activities. Analysis of the profiles suggests that the concept of toxic heavy metals and safe nontoxic alternatives based on lighter metals should be re‐evaluated. Comparison of the toxicological data indicates that palladium, platinum, and gold compounds, often considered heavy and toxic, may in fact be not so dangerous, whereas complexes of nickel and copper, typically assumed to be green and sustainable alternatives, may possess significant toxicities, which is also greatly affected by the solubility in water and biological fluids. It appears that the development of new catalysts and novel applications should not rely on the existing assumptions concerning toxicity/nontoxicity. Overall, the available experimental data seem insufficient for accurate evaluation of biological activity of these metals and its modulation by the ligands. Without dedicated experimental measurements for particular metal/ligand frameworks, toxicity should not be used as a “selling point” when describing new catalysts.     

Calorimetric, spectroscopic, and model studies provide insight into the transport of Ti(IV) by human serum transferrin

Evidence suggests that transferrin can bind Ti(IV) in an unhydrolyzed form (without bound hydroxide or oxide) or in a hydrolyzed form. Ti(IV) coordination by N,N'-di(o-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED) at different pH values models the two forms of Ti(IV)-loaded transferrin spectrally and structurally. 13C NMR and stopped-flow kinetic experiments reveal that when the metal is delivered to the protein using an unhydrolyzed source, Ti(IV) can coordinate in the typical distorted octahedral environment with a bound synergistic anion. The crystal structure of TiHBED obtained at low pH models this type of coordination. The solution structure of the complex compares favorably with the solid state from pH 3.0 to 4.0, and the complex can be reduced with E1/2 = -641 mV vs NHE. Kinetic and thermodynamic competition studies at pH 3.0 reveal that Ti(citrate)3 reacts with HBED via a dissociative mechanism and that the stability of TiHBED (log beta = 34.024) is weaker than that of the Fe(III) complex. pH stability studies show that Ti(IV) hydrolyzes ligand waters at higher pH but still remains bound to HBED until pH 9.5. Similarly, at a pH greater than 8.0 the synergistic anion that binds Ti(IV) in transferrin is readily displaced by irreversible metal hydrolysis although the metal remains bound to the protein until pH 9.5. Thermal denaturation studies conducted optically and by differential scanning calorimetry reveal that Ti(IV)-bound transferrin experiences only minimal enhanced thermal stability unlike when Fe(III) is bound. The C- and N-lobe transition Tm values shift to a few degrees higher. The stability, competition, and redox studies performed provide insight into the possible mechanism of Ti2-Tf transport in cells.     

High-order structure and dissociation of gaseous peptide aggregates that are hidden in mass spectra

Injected-ion mobility and high-pressure ion mobility techniques have been used to examine the conformations of bradykinin, insulin chain A, and several other peptide ions in the gas phase. Under the experimental conditions employed, evidence for multimer formation in the mass spectra of peptides is minimal or absent altogether. However, ion mobility distributions show that aggregates of peptides (containing a single charge per monomer unit) are observed at the same mass-to-charge ratios as the singly charged parent ions. Collision cross sections for these clusters show that they have tightly packed roughly spherical conformations. We have bracketed the average density as 0. 87 ρ < ρ < 1. 00 g cm^?3. In some cases, specific stable aggregate forms within a cluster size can be distinguished indicating that some high order structures are favored in the gas phase. Multimer formation between different sizes of polyalanine peptides shows no evidence for size specificity in aggregate formation. Collisional and thermal excitation studies have been used to examine structural transitions and dissociation of the multimers. Aggregates appear to dissociate via loss of singly charged monomers. The observation that peptide multimers can be concealed in mass spectral data requires that fragmentation patterns and reactivity studies of singly charged monomers be undertaken with care.