Charge Site Mass Spectra: Conformation-Sensitive Components of the Electron Capture Dissociation Spectrum of a Protein

A conventional electron capture dissociation (ECD) spectrum of a protein is uniquely characteristic of the first dimension of its linear structure. This sequence information is indicated by summing the primary c ^m+ and z ^m+? products of cleavage at each of its molecular ion’s inter-residue bonds. For example, the ECD spectra of ubiquitin (M?+?nH)ⁿ⁺ ions, n?=?7–13, provide sequence characterization of 72 of its 75 cleavage sites from 1843 ions in seven c ^(1–7)+ and eight z ^(1–8)+? spectra and their respective complements. Now we find that each of these c/z spectra is itself composed of “charge site (CS)” spectra, the c ^m+ or z ^m+? products of electron capture at a specific protonated basic residue. This charge site has been H-bonded to multiple other residues, producing multiple precursor ion forms; ECD at these residues yields the multiple products of that CS spectrum. Closely similar CS spectra are often formed from a range of charge states of ubiquitin and KIX ions; this indicates a common secondary conformation, but not the conventional α-helicity postulated previously. CS spectra should provide new capabilities for comparing regional conformations of gaseous protein ions and delineating ECD fragmentation pathways.

Synthesis of water‐soluble zwitterionic polysiloxanes

A series of water‐soluble siloxane polymers with pendent phosphorylcholine (PC) and sulfobetaine (SB) zwitterions was prepared using thiol‐ene “click” chemistry. Specifically, well‐defined vinyl‐substituted siloxane homopolymers and block copolymers were functionalized with small molecule zwitterionic thiols at room temperature. Rapid and quantitative substitution of the pendent vinyl groups was achieved, and zwitterionic polysiloxanes of narrow molecular weight distribution were obtained. The PC‐ and SB‐substituted polymers were found to be readily soluble in pure, salt‐free water. Critical micelle concentrations (CMCs) of these polymers in water were measured using a pyrene fluorescence probe, with CMC values estimated to be <0.01 g/L. Polymer aggregates were studied by dynamic light scattering, and the micelles generated from the PC block copolymers were visualized, after drying, by transmission electron microscopy. Aqueous solutions of these zwitterionic polysiloxanes significantly reduced the oil‐water interfacial surface tension, functioning as polymer amphiphiles that lend stability to oil‐in‐water emulsions. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 127–134     

The isotope exchange depth profiling (IEDP) technique using SIMS and LEIS

The determination of the mass transport kinetics of oxide materials for use in electrochemical systems such as fuel cells, sensors and oxygen separators is a significant challenge. Several techniques have been proposed to derive these data experimentally with only the oxygen isotope exchange depth profile technique coupled with secondary ion mass spectrometry (SIMS) providing a direct measure of these kinetic parameters. Whilst this allows kinetic information to be obtained, there is a lack of knowledge of the surface chemistry of these complex processes. The advent of low-energy ion scattering (LEIS) now offers the opportunity of correlating exchange kinetics with chemical processes at materials atomic surfaces, giving unprecedented levels of information on electrochemical systems with isotopic discrimination. Here, the challenges of these techniques, including sample preparation, are discussed and the advantages of the combined approach of SIMS and LEIS illustrated with reference to key literature data.     

Evaluation of a multiple spin- and gradient-echo (SAGE) EPI acquisition with SENSE acceleration: Applications for perfusion imaging in and outside the brain

Perfusion-based changes in MR signal intensity can occur in response to the introduction of exogenous contrast agents and endogenous tissue properties (e.g. blood oxygenation). MR measurements aimed at capturing these changes often implement single-shot echo planar imaging (ssEPI). In recent years ssEPI readouts have been combined with parallel imaging (PI) to allow fast dynamic multi-slice imaging as well as the incorporation of multiple echoes. A multiple spin- and gradient-echo (SAGE) EPI acquisition has recently been developed to allow measurement of transverse relaxation rate (R₂ and R₂^?) changes in dynamic susceptibility contrast (DSC)-MRI experiments in the brain. With SAGE EPI, the use of PI can influence image quality, temporal resolution, and achievable echo times. The effect of PI on dynamic SAGE measurements, however, has not been evaluated. In this work, a SAGE EPI acquisition utilizing SENSE PI and partial Fourier (PF) acceleration was developed and evaluated. Voxel-wise measures of R₂ and R₂^? in healthy brain were compared using SAGE EPI and conventional non-EPI multiple echo acquisitions with varying SENSE and PF acceleration. A conservative SENSE factor of 2 with PF factor of 0.73 was found to provide accurate measures of R₂ and R₂^? in white (WM) (r_R2 = [0.55–0.79], r_R2? = [0.47–0.71]) and gray (GM) matter (r_R2 = [0.26–0.59], r_R2? = [0.39–0.74]) across subjects. The combined use of SENSE and PF allowed the first dynamic SAGE EPI measurements in muscle, with a SENSE factor of 3 and PF factor of 0.6 providing reliable relaxation rate estimates when compared to multi-echo methods. Application of the optimized SAGE protocol in DSC-MRI of high-grade glioma patients provided T₁ leakage-corrected estimates of CBV and CBF as well as mean vessel diameter (mVD) and simultaneous measures of DCE-MRI parameters K^trans and v_e. Likewise, application of SAGE in a muscle reperfusion model allowed dynamic measures of R₂′, a parameter that has been shown to correlate with muscle oxy-hemoglobin saturation.     

Derivation of Smoluchowski equations with corrections for Fokker-Planck and BGK collision models

The time evolution of the phase space distribution function for a classical particle in contact with a heat bath and in an external force field can be described by a kinetic equation. From this starting point, for either Fokker-Planck or BGK (Bhatnagar-Gross-Krook) collision models, we derive, with a projection operator technique, Smoluchowski equations for the configuration space density with corrections in reciprocal powers of the friction constant. For the Fokker-Planck model our results in Laplace space agree with Brinkman, and in the time domain, with Wilemski and Titulaer. For the BGK model, we find that the leading term is the familiar Smoluchowski equation, but the first correction term differs from the Fokker-Planck case primarily by the inclusion of a fourth order space derivative or super Burnett term. Finally, from the corrected Smoluchowski equations for both collision models, in the spirit of Kramers, we calculate the escape rate over a barrier to fifth order in the reciprocal friction constant, for a particle initially in a potential well.     

Formation of H and D atoms in pyrolysis of 1,3-butadiene and 1,3 butadiene-1,1,4,4,-d4 behind shock waves

Highly dilute mixtures of 1,3-butadiene and 1,3-butadiene-1,1,4,4-d₄ were pyrolyzed behind reflected and incident shock waves, respectively. Concentrations of H and D atoms were measured by resonance absorption spectroscopy. In the early stages of the reaction, nearly equal amounts of H and D were formed from CD₂CHCHCD₂, indicating that loss of H from C₂ followed by loss of D from C₁ is a more important reaction than breaking of the central C? C bond. Overall, rate constants for atom-forming reactions are much slower than rate constants for disappearance of butadiene in earlier experiments, suggesting that most of the butadiene disappears by processes that do not involve H or D atoms or by radicals that produce them rapidly.