| 1. |
- Wessel, Jennifer, et al.
(författare)
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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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| 2. |
- Mironov, Oleg A., et al.
(författare)
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Using Reduced Catalysts for Oxidation Reactions : Mechanistic Studies of the “Periana-Catalytica” System for CH4 Oxidation
- 2013
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 135:39, s. 14644-14658
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Tidskriftsartikel (refereegranskat)abstract
- Designing oxidation catalysts based on CH activation with reduced, low oxidation state species is a seeming dilemma given the proclivity for catalyst deactivation by overoxidation. This dilemma has been recognized in the Shilov system where reduced Pt-II is used to catalyze methane functionalization. Thus, it is generally accepted that key to replacing Pt-IV in that system with more practical oxidants is ensuring that the oxidant does not over-oxidize the reduced Pt-II species. The “Periana-Catalytica” system, which utilizes (bpym)-(PtCl2)-Cl-II in concentrated sulfuric acid solvent at 200 degrees C, is a highly stable catalyst for the selective, high yield oxy-functionalization of methane. In lieu of the over-oxidation dilemma, the high stability and observed rapid oxidation of (bpym)(PtCl2)-Cl-II to Pt-IV in the absence of methane would seem to contradict the originally proposed mechanism involving CH activation by a reduced Pt-II species. Mechanistic studies show that the originally proposed mechanism is incomplete and that while CH activation does proceed with Pt-II there is a solution to the over oxidation dilemma. Importantly, contrary to the accepted view to minimize Pt-II overoxidation, these studies also show that increasing that rate could increase the rate of catalysis and catalyst stability. The mechanistic basis for this counterintuitive prediction could help to guide the design of new catalysts for alkane oxidation that operate by CH activation.
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| 3. |
- Tenn, William J., III, et al.
(författare)
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Oxy-Functionalization of Nucleophilic Rhenium(I) Metal Carbon Bonds Catalyzed by Selenium(IV)
- 2009
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 131:7, s. 2466-2468
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Tidskriftsartikel (refereegranskat)abstract
- We report that SeO(2) catalyzes the facile oxy-functionalization of (CO)(5)Re(I)-Me(delta-) with IO(4)(-) to generate methanol. Mechanistic studies and DFT calculations reveal that catalysis involves methyl group transfer from Re to the electrophilic Se center followed by oxidation and subsequent reductive functionalization of the resulting CH(3)Se(VI) species. Furthermore, (CO)(3)Re(I)(Bpy)-R (R = ethyl, n-propyl, and aryl) complexes show analogous transfer to SeO(2) to generate the primary alcohols. This represents a new strategy for the oxy-functionalization of M-R(delta-) polarized bonds.
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| 4. |
- Ahlquist, Mårten, et al.
(författare)
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C-H activation in strongly acidic media. The co-catalytic effect of the reaction medium
- 2009
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Ingår i: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1359-7345 .- 1364-548X. ; :17, s. 2373-2375
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Tidskriftsartikel (refereegranskat)abstract
- Quantum mechanical (QM) results are used to establish the role of sulfuric acid solvent in facilitating the reaction between Pt(II)(bpym)Cl(2) (bpym = 2,2'-bipyrimidinyl) and methane; coordination of methane to the platinum catalyst is found to be catalyzed by the acidic medium.
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| 5. |
- Ahlquist, Mårten, et al.
(författare)
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Product Protection, the Key to Developing High Performance Methane Selective Oxidation Catalysts
- 2009
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 131:47, s. 17110-17115
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Tidskriftsartikel (refereegranskat)abstract
- Selective, direct conversion of methane to methanol might seem an impossible task since the C-H bond energy of methane is 105 kcal mol(-1) compared to the C-H bond energy for methanol of 94. We show here that the Catalytica catalyst is successful because the methanol is protected as methyl bisulfate, which is substantially less reactive than methanol toward the catalyst. This analysis suggests a limiting performance for systems that operate by this type of protection that is well above the Catalytica system.
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| 6. |
- Cheng, Mu-Jeng, et al.
(författare)
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Carbon-Oxygen Bond Forming Mechanisms in Rhenium Oxo-Alkyl Complexes
- 2010
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Ingår i: Organometallics. - : American Chemical Society (ACS). - 0276-7333 .- 1520-6041. ; 29:9, s. 2026-2033
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Tidskriftsartikel (refereegranskat)abstract
- Three C X bond formation mechanisms observed in the oxidation of (HBpz(3))ReO(R)(OTf) [HBpz(3) = hydrotris(1-pyrazolypborate; R = Me, Et, and iPr; OTf = OSO(2)CF(3)] by dimethyl sulfoxide (DMSO) were investigated using quantum mechanics (M06//B3LYP DFT) combined with solvation (using the PBF Poisson Boltzmann polarizable continuum solvent model). For R = Et we find the alkyl group is activated through alpha-hydrogen abstraction by external base OTf(-) with a free energy barrier of only 12.0 kcal/mol, leading to formation of acetaldehyde. Alternatively, ethyl migration across the M=O bond (leading to the formation of acetaldehyde and ethanol) poses a free energy barrier of 22.1 kcal/mol, and the previously proposed alpha-hydrogen transfer to oxo (a 2+2 forbidden reaction) poses a barrier of 44.9 kcal/mol. The rate-determining step to formation of the final product acetaldehyde is an oxygen atom transfer from DMSO to the ethylidene, with a free energy barrier of 15.3 kcal/mol. When R = iPr, the alkyl 1,2-migration pathway becomes the more favorable pathway (both kinetically and thermodynamically), with a free energy barrier (Delta G(double dagger) = 11.8 kcal/mol) lower than alpha-hydrogen abstraction by OTf(-) (Delta G(double dagger) = 13.5 kcal/mol). This suggests the feasibility of utilizing this type of migration to functionalize M-R to M-OR. We also considered the nucleophilic attack of water and ammonia on the Re-ethylidene alpha-carbon as a means of recovering two-electron-oxidized products from an alkane oxidation. Nucleophilic attack (with internal deprotonation of the nucleophile) is exothermic. However, the subsequent protonolysis of the Re alkyl bond (to liberate an alcohol or amine) poses a barrier of 37.0 or 42.4 kcal/mol, respectively. Where comparisons are possible, calculated free energies agree very well with experimental measurements.
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| 7. |
- Hirani, Bhavna, et al.
(författare)
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Cyclometallated iridium and platinum complexes with noninnocent ligands
- 2007
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Ingår i: Inorganic Chemistry. - : American Chemical Society (ACS). - 1520-510X .- 0020-1669. ; 46:10, s. 3865-3875
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Tidskriftsartikel (refereegranskat)abstract
- The electronic properties of the cyclometalated ((CN)-N-and) complexes of iridium and platinum metals with a catechol ligand have been studied experimentally and computationally. The synthesis and characterization of (p-tolylpyridine)Ir(3,5-di-tert-butylcatechol) (abbreviated Ir-sq) and (2,4-diflorophenylpyridine)Pt(3,5-di-tert-butylcatechol) (abbreviated Pt-sq) are reported along with their structural, spectral, and electrochemical properties. Reaction of the 3,5-di-tert-butylcatechol (DTBCat) ligand with the prepared cyclometalated metal complex was carried out in air in the presence of a base. The resulting complexes are air stable and are paramagnetic with the unpaired electron residing mainly on the catechol ligand. The bond lengths obtained from X-ray structure analysis and the theoretical results suggest the semiquinone form of the catechol ligand. Low-energy, intense (similar to 10(3) M-1 cm(-1)) transitions are observed in the visible to near-infrared region (600-700 nm) of the absorption spectra of the metal complexes. Electrochemically, the complexes exhibit a reversible reduction of the semiquinone form to the catechol form of the ligand and an irreversible oxidation to the unstable quinone form of the ligand. The noninnocent catechol ligand plays a significant role in the electronic properties of the metal complexes. Density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations on the two open-shell molecules provide the ground-state and excited-state energies of the molecular orbitals involved in the observed low-energy transitions. The spin density in the two complexes resides mainly on the catechol ligand. The intense transition arises from excitation of the beta electron from a HOMO-n (n = 1 or 2 here) to the LUMO, rather than from the excitation of the unpaired alpha electron.
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| 8. |
- Johnson, Samantha, et al.
(författare)
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Design of robust 2,2′-bipyridine ligand linkers for the stable immobilization of molecular catalysts on silicon(111) surfaces
- 2021
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Ingår i: Physical Chemistry Chemical Physics. - : Royal Society of Chemistry (RSC). - 1463-9076 .- 1463-9084. ; 23:16, s. 9921-9929
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Tidskriftsartikel (refereegranskat)abstract
- The attachment of the 2,2′-bipyridine (bpy) moieties to the surface of planar silicon(111) (photo)electrodes was investigated usingab initiosimulations performed on a new cluster model for methyl-terminated silicon. Density functional theory (B3LYP) with implicit solvation techniques indicated that adventitious chlorine atoms, when present in the organic linker backbone, led to instability at very negative potentials of the surface-modified electrode. In prior experimental work, chlorine atoms were present as a trace surface impurity due to required surface processing chemistry, and thus could plausibly result in the observed surface instability of the linker. Free energy calculations for the Cl-atom release process with model silyl-linker constructs revealed a modest barrier (14.9 kcal mol−1) that decreased as the electrode potential became more negative. A small library of new bpy-derived structures has additionally been explored computationally to identify strategies that could minimize chlorine-induced linker instability. Structures with fluorine substituents are predicted to be more stable than their chlorine analogues, whereas fully non-halogenated structures are predicted to exhibit the highest stability. The behavior of a hydrogen-evolving molecular catalyst Cp*Rh(bpy) (Cp* = pentamethylcyclopentadienyl) immobilized on a silicon(111) cluster was explored theoretically to evaluate differences between the homogeneous and surface-attached behavior of this species in a tautomerization reaction observed under reductive conditions for catalytic H2evolution. The calculated free energy difference between the tautomers is small, hence the results suggest that use of reductively stable linkers can enable robust attachment of catalysts while maintaining chemical behavior on the electrode similar to that exhibited in homogeneous solution.
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| 9. |
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| 10. |
- Raymand, David, 1981-, et al.
(författare)
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Hydroxylation Structure and Proton Transfer Reactivity at the Zinc Oxide-Water Interface
- 2011
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Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society. - 1932-7447 .- 1932-7455. ; 115:17, s. 8573-8579
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Tidskriftsartikel (refereegranskat)abstract
- The hydroxylation structural features of the first adsorption layer and its connection to proton transfer reactivity has been studied for the ZnO–liquid water interface at room temperature. Molecular Dynamics simulations employing the ReaxFF forcefield were performed for water on seven ZnO surfaces with varying step concentration. At higher water coverage a higher level of hydroxylation was found, in agreement with previous experimental results. We have also calculated the free energy barrier for transferring a proton to the surface, showing that stepped surfaces stabilizes the hydroxylated state and decreases the water dissociation barrier. On highly stepped surfaces the barrier is only 2 kJ/mol or smaller. Outside the first adsorption layer no dissociation events were observed during almost 100 ns of simulation time; this indicates that these reactions are much more likely if catalysed by the metal oxide surface. Also, when exposed to a vacuum, the less stepped surfaces stabilizes adsorption beyond monolayer coverage.
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