Local convexity and starshaped sets

Previously [7] we proved among other results that a closed connected set inE _n which has a unique point of local nonconvexity is starshaped. Here we characterize a fairly large class of plane sets whose points of local nonconvexity are so arranged that starshapedness follows. This theory determines as a special case the simple closed polygonal regions which are starshaped. In order to proceed simply we utilize the following notations and definitions. The preparation of this paper was supported in part by NSF Grant GP-1988.     

Carboxylate Switch between Hydro‐ and Carbopalladation Pathways in Regiodivergent Dimerization of Alkynes

Experimental and theoretical investigation of the regiodivergent palladium‐catalyzed dimerization of terminal alkynes is presented. Employment of N‐heterocyclic carbene‐based palladium catalyst in the presence of phosphine ligand allows for highly regio‐ and stereoselective head‐to‐head dimerization reaction. Alternatively, addition of carboxylate anion to the reaction mixture triggers selective head‐to‐tail coupling. Computational studies suggest that reaction proceeds via the hydropalladation pathway favoring head‐to‐head dimerization under neutral reaction conditions. The origin of the regioselectivity switch can be explained by the dual role of carboxylate anion. Thus, the removal of hydrogen atom by the carboxylate directs reaction from the hydropalladation to the carbopalladation pathway. Additionally, in the presence of the carboxylate anion intermediate, palladium complexes involved in the head‐to‐tail dimerization display higher stability compared to their analogues for the head‐to‐head reaction.     

Lysine residues in the N‐terminal huntingtin amphipathic α‐helix play a key role in peptide aggregation

Huntington's disease is a genetic neurodegenerative disorder caused by an expansion in a polyglutamine domain near the N‐terminus of the huntingtin (htt) protein that results in the formation of protein aggregates. Here, htt aggregate structure has been examined using hydrogen–deuterium exchange techniques coupled with tandem mass spectrometry. The focus of the study is on the 17‐residue N‐terminal flanking region of the peptide that has been shown to alter htt aggregation kinetics and morphology. A top‐down sequencing strategy employing electron transfer dissociation is utilized to determine the location of accessible and protected hydrogens. In these experiments, peptides aggregate in a deuterium‐rich solvent at neutral pH and are subsequently subjected to deuterium–hydrogen back‐exchange followed by rapid quenching, disaggregation, and tandem mass spectrometry analysis. Electrospray ionization of the peptide solution produces the [M + 5H]⁵⁺ to [M + 10H]¹⁰⁺ charge states and reveals the presence of multiple peptide sequences differing by single glutamine residues. The [M + 7H]⁷⁺ to [M + 9]⁹⁺ charge states corresponding to the full peptide are used in the electron transfer dissociation analyses. Evidence for protected residues is observed in the 17‐residue N‐terminal tract and specifically points to lysine residues as potentially playing a significant role in htt aggregation. Copyright © 2015 John Wiley & Sons, Ltd.     

Coupling desorption electrospray ionization with ion mobility/mass spectrometry for analysis of protein structure: evidence for desorption of folded and denatured States

A desorption electrospray ionization (DESI) source has been coupled to an ion mobility time-of-flight mass spectrometer for the analysis of proteins. Analysis of solid-phase horse heart cytochrome c and chicken egg white lysozyme proteins with different DESI solvents and conditions shows similar mass spectra and charge state distributions to those formed when using electrospray to analyze these proteins in solution. The ion mobility data show evidence for compact ion structures [when the surface is exposed to a spray that favors retention of "nativelike" structures (50:50 water:methanol)] or elongated structures [when the surface is exposed to a spray that favors "denatured" structures (49:49:2 water:methanol:acetic acid)]. The results suggest that the DESI experiment is somewhat gentler than ESI and under appropriate conditions, it is possible to preserve structural information throughout the DESI process. Mechanisms that are consistent with these results are discussed.     

Solvent dependence of the charge-transfer properties of a quaterthiophene–anthraquinone dyad

An electron donor–acceptor dyad (quaterthiophene–anthraquinone) mediates ultrafast intramolecular photoinduced charge separation and consequent charge recombination when in polar or moderately polar solvents. Alternatively, non-polar media completely impedes the initial photoinduced electron transfer by causing enough destabilization of the charge-transfer state and shifting its energy above the energy of the lowest locally excited singlet state. Furthermore, femtosecond transient-absorption spectroscopy reveals that for the solvents mediating the initial photoinduced electron-transfer process, the charge recombination rates were slower than the rates of charge separation. This behavior of donor–acceptor systems is essential for solar-energy-conversion applications. For the donor–acceptor dyad described in this study, the electron-transfer driving force and reorganization energy place the charge-recombination processes in the Marcus inverted region.     

Comparison of two yeast MnSODs: mitochondrial Saccharomyces cerevisiae versus cytosolic Candida albicans

Human MnSOD is significantly more product-inhibited than bacterial MnSODs at high concentrations of superoxide (O(2)(-)). This behavior limits the amount of H(2)O(2) produced at high [O(2)(-)]; its desirability can be explained by the multiple roles of H(2)O(2) in mammalian cells, particularly its role in signaling. To investigate the mechanism of product inhibition in MnSOD, two yeast MnSODs, one from Saccharomyces cerevisiae mitochondria (ScMnSOD) and the other from Candida albicans cytosol (CaMnSODc), were isolated and characterized. ScMnSOD and CaMnSODc are similar in catalytic kinetics, spectroscopy, and redox chemistry, and they both rest predominantly in the reduced state (unlike most other MnSODs). At high [O(2)(-)], the dismutation efficiencies of the yeast MnSODs surpass those of human and bacterial MnSODs, due to very low level of product inhibition. Optical and parallel-mode electron paramagnetic resonance (EPR) spectra suggest the presence of two Mn(3+) species in yeast Mn(3+)SODs, including the well-characterized 5-coordinate Mn(3+) species and a 6-coordinate L-Mn(3+) species with hydroxide as the putative sixth ligand (L). The first and second coordination spheres of ScMnSOD are more similar to bacterial than to human MnSOD. Gln154, an H-bond donor to the Mn-coordinated solvent molecule, is slightly further away from Mn in yeast MnSODs, which may result in their unusual resting state. Mechanistically, the high efficiency of yeast MnSODs could be ascribed to putative translocation of an outer-sphere solvent molecule, which could destabilize the inhibited complex and enhance proton transfer from protein to peroxide. Our studies on yeast MnSODs indicate the unique nature of human MnSOD in that it predominantly undergoes the inhibited pathway at high [O(2)(-)].     

Catalytic hydrofunctionalization of alkynes through P-H bond addition: the unique role of orientation and properties of the phosphorus group in the insertion step

The puzzling question of alkyne insertion into Pd-P and Pd-H bonds leading to the formation of new Pd-C, C-P, and C-H bonds was explored by theoretical calculations at the CCSD(T) and B3LYP levels of theory. The key factors responsible for selectivity of catalytic hydrofunctionalization of alkynes were resolved and studied in details for the models of hydrophosphorylation, hydrophosphinylation, and hydrophospination reactions. In contrast with the generally accepted mechanistic picture, the calculations have shown that several pathways are possible depending on the nature and geometrical arrangement of the phosphorus group. It was found that the product of alkyne insertion into the metal-hydrogen bond should be easily formed under kinetic-control conditions, while the product of alkyne insertion into the metal-phosphorus bond may be formed in certain cases under thermodynamic control. For the first time, the calculations have revealed the role of the oxygen atom in the reactivity of P=P(O)R(2) groups and the role of the interactions involving the lone pair of the P=PR(2) group in the reagent. The fundamental properties of the Pd-P, C-P, and P-H bonds were reported, and the larger bond strength upon increasing the number of oxygen atoms bound to phosphorus (P=PR(2), P(O)R(2), and P(O)(OR)(2)) have been shown. The relationship between bond energy, acidity, and reactivity of the studied phosphorus compounds has been determined.     

Overtone Mobility Spectrometry: Part 4. OMS-OMS Analyses of Complex Mixtures

A new, two-dimensional overtone mobility spectrometry (OMS-OMS) instrument is described for the analysis of complex peptide mixtures. OMS separations are based on the differences in mobilities of ions in the gas phase. The method utilizes multiple drift regions with modulated drift fields such that only ions with appropriate mobilities are transmitted to the detector. Here we describe a hybrid OMS-OMS combination that utilizes two independently operated OMS regions that are separated by an ion activation region. Mobility-selected ions from the first OMS region are exposed to energizing collisions and may undergo structural transitions before entering the second OMS region. This method generates additional peak capacity and allows for higher selectivity compared with the one-dimensional OMS method. We demonstrate the approach using a three-protein tryptic digest spiked with the peptide Substance P. The [M + 3H]³⁺ ion from Substance P can be completely isolated from other components in this complex mixture prior to introduction into the mass spectrometer.     

Overtone Mobility Spectrometry: Part 5. Simulations and Analytical Expressions Describing Overtone Limits

Mathematical expressions for the analytical duty cycle associated with different overtones in overtone mobility spectrometry are derived from the widths of the transmitted packets of ions under different instrumental operating conditions. Support for these derivations is provided through ion trajectory simulations. The outcome of the theory and simulations indicates that under all operating conditions there exists a limit or maximum observable overtone that will result in ion transmission. Implications of these findings on experimental design are discussed.      

Transition metal ‘cocktail’-type catalysis

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