Copper salts find widespread use in Pd-catalyzed oxidation reactions, and they are typically used as oxidants or redox-active cocatalysts. Here, we probe the origin of a dramatic acceleration effect ...of Cu(OTf)2 in the C–H/C–H aerobic oxidative coupling of o-xylene. NMR spectroscopic analysis of the PdII catalyst in the presence of Cu(OTf)2, together with other experimental and DFT computational studies of the catalytic reaction, show that Cu(OTf)2 activates the PdII catalyst for C–H activation via a non-redox pathway and has negligible impact on catalyst reoxidation. These observations led to the testing of other metal triflate salts as cocatalysts, the results of which show that Fe(OTf)3 is even more effective than Cu(OTf)2.
Objective: To summarize the accumulated data on metabolic syndrome prevalence in patients with schizophrenia, examine evidence for a biological contribution of the mental illness to metabolic risk ...and review novel options available for management of prediabetic states.
Method: A Medline search using metabolic syndrome, insulin resistance and insulin sensitivity cross‐referenced with schizophrenia was performed on articles published between 1990 and May 2008.
Results: Recent evidence indicates that schizophrenia increases predisposition towards metabolic dysfunction independent of environmental exposure. Both fasting and non‐fasting triglycerides have emerged as important indicators of cardiometabolic risk, while metformin, thiazolidinediones and GLP‐1 modulators may prove promising tools for managing insulin resistance.
Conclusion: Because of lifestyle, disease and medication effects, schizophrenia patients have significant risk for cardiometabolic disease. Routine monitoring, preferential use of metabolically neutral antipsychotics and lifestyle education are critical to minimizing risk, with a possible role for antidiabetic medications for management of insulin resistant states that do not respond to other treatment strategies.
A copper-catalyzed method for the preparation of ynamides has been identified that proceeds via aerobic oxidative coupling of terminal alkynes with various nitrogen nucleophiles, including cyclic ...carbamates, amides and ureas, and N-alkyl-arylsulfonamides and indoles.
Quinones participate in diverse electron transfer and proton-coupled electron transfer processes in chemistry and biology. To understand the relationship between these redox processes, an ...experimental study was carried out to probe the 1 e– and 2 e–/2 H+ reduction potentials of a number of common quinones. The results reveal a non-linear correlation between the 1 e– and 2 e–/2 H+ reduction potentials. This unexpected observation prompted a computational study of 134 different quinones, probing their 1 e– reduction potentials, pK a values, and 2 e–/2 H+ reduction potentials. The density functional theory calculations reveal an approximately linear correlation between these three properties and an effective Hammett constant associated with the quinone substituent(s). However, deviations from this linear scaling relationship are evident for quinones that feature intramolecular hydrogen bonding, halogen substituents, charged substituents, and/or sterically bulky substituents. These results, particularly the different substituent effects on the 1 e– versus 2 e–/2 H+ reduction potentials, have important implications for designing quinones with tailored redox properties.
Pd-catalyzed aerobic oxidative coupling of arenes provides efficient access to biaryl compounds. The biaryl product forms via C–H activation of two arenes to afford a PdIIArAr′ intermediate, which ...then undergoes C–C reductive elimination. The key PdIIArAr′ intermediate could form via a “monometallic” pathway involving sequential C–H activation at a single PdII center, or via a “bimetallic” pathway involving parallel C–H activation at separate PdII centers, followed by a transmetalation step between two PdII–aryl intermediates. Here, we investigate the oxidative coupling of o-xylene catalyzed by a PdX2/2-fluoropyridine catalyst (X = trifluoroacetate, acetate). Kinetic studies, H/D exchange experiments, and kinetic isotope effects provide clear support for a bimetallic/transmetalation mechanism.
A Cu-catalyzed method has been identified for aerobic oxidative dimerization of carbazoles and diarylamines to the corresponding N–N coupled bicarbazoles and tetraarylhydrazines. The reactions ...proceed under mild conditions (1 atm O2, 60–80 °C) with a catalyst composed of CuBr·dimethylsulfide and N,N-dimethylaminopyridine. Reactions between carbazole and diarylamines show unusually selective cross-coupling, even with a 1:1 ratio of the two substrates. This behavior was found to arise from reversible formation of the tetraarylhydrazine. Formation of this species is kinetically favored, but cleavage of the N–N bond under the reaction conditions leads to selective formation of the thermodynamically favored cross-coupling product.
Affibody molecules are a class of engineered affinity proteins with proven potential for therapeutic, diagnostic and biotechnological applications. Affibody molecules are small (6.5
kDa) single ...domain proteins that can be isolated for high affinity and specificity to any given protein target. Fifteen years after its discovery, the Affibody technology is gaining use in many groups as a tool for creating molecular specificity wherever a small, engineering compatible tool is warranted. Here we summarize recent results using this technology, propose an Affibody nomenclature and give an overview of different HER2-specific Affibody molecules. Cumulative evidence suggests that the three helical scaffold domain used as basis for these molecules is highly suited to create a molecular affinity handle for vastly different applications.
Synthetic methods that achieve oxidative 1,2-difunctionalization of alkenes are very powerful in organic chemistry. Here we report the first examples of intermolecular Pd-catalyzed aminoacetoxylation ...of alkenes with phthalimide as the nitrogen source and PhI(OAc)2 as the stoichiometric oxidant and source of acetate. These reactions are highly regio- and diastereoselective, and mechanistic studies reveal that the reaction proceeds via cis-aminopalladation of the alkene followed by oxidative cleavage of the intermediate Pd−C bond with inversion of stereochemistry.
A palladium(II) catalyst system has been identified for aerobic dehydrogenation of substituted cyclohexenes to the corresponding arene derivatives. Use of sodium anthraquinone-2-sulfonate (AMS) as a ...cocatalyst enhances the product yields. A wide range of functional groups are tolerated in the reactions, and the scope and limitations of the method are described. The catalytic dehydrogenation of cyclohexenes is showcased in an efficient route to a phthalimide-based TRPA1 activity modulator.
NiFe oxyhydroxide materials are highly active electrocatalysts for the oxygen evolution reaction (OER), an important process for carbon-neutral energy storage. Recent spectroscopic and computational ...studies increasingly support iron as the site of catalytic activity but differ with respect to the relevant iron redox state. A combination of hybrid periodic density functional theory calculations and spectroelectrochemical experiments elucidate the electronic structure and redox thermodynamics of Ni-only and mixed NiFe oxyhydroxide thin-film electrocatalysts. The UV/visible light absorbance of the Ni-only catalyst depends on the applied potential as metal ions in the film are oxidized before the onset of OER activity. In contrast, absorbance changes are negligible in a 25% Fe-doped catalyst up to the onset of OER activity. First-principles calculations of proton-coupled redox potentials and magnetizations reveal that the Ni-only system features oxidation of Ni2+ to Ni3+, followed by oxidation to a mixed Ni3+/4+ state at a potential coincident with the onset of OER activity. Calculations on the 25% Fe-doped system show the catalyst is redox inert before the onset of catalysis, which coincides with the formation of Fe4+ and mixed Ni oxidation states. The calculations indicate that introduction of Fe dopants changes the character of the conduction band minimum from Ni-oxide in the Ni-only to predominantly Fe-oxide in the NiFe electrocatalyst. These findings provide a unified experimental and theoretical description of the electrochemical and optical properties of Ni and NiFe oxyhydroxide electrocatalysts and serve as an important benchmark for computational characterization of mixed-metal oxidation states in heterogeneous catalysts.
PDF
