Combined effects of a ketogenic diet and exercise training alter mitochondrial and peroxisomal substrate oxidative capacity in skeletal muscle.

Ketogenic diets (KDs) are reported to improve body weight, fat mass, and exercise performance in humans. Unfortunately, most rodent studies have used a low-protein KD, which does not recapitulate diets used by humans. Since skeletal muscle plays a critical role in responding to macronutrient perturbations induced by diet and exercise, the purpose of this study was to test if a normal-protein KD (NPKD) impacts shifts in skeletal muscle substrate oxidative capacity in response to exercise training (ExTr).

Impact of Multiple Hydrogen Bonds with Fluoride on Catalysis: Insight from NMR Spectroscopy.

Hydrogen-bonding interactions have been explored in catalysis, enabling complex chemical reactions. Recently, enantioselective nucleophilic fluorination with metal alkali fluoride has been accomplished with BINAM-derived bisurea catalysts, presenting up to four NH hydrogen-bond donors (HBDs) for fluoride. These catalysts bring insoluble CsF and KF into solution, control fluoride nucleophilicity, and provide a chiral microenvironment for enantioselective fluoride delivery to the electrophile.

Response of Liver Metabolic Pathways to Ketogenic Diet and Exercise Are Not Additive.

Purpose: Studies suggest ketogenic diets (KD) produce favorable outcomes (health and exercise performance); however, most rodent studies have used a low-protein KD, which does not reflect the normal- to high-protein KD used by humans. Liver has an important role in ketoadaptation due to its involvement in gluconeogenesis and ketogenesis. This study was designed to test the hypothesis that exercise training (ExTr) while consuming a normal-protein KD (NPKD) would induce additive/synergistic responses in liver metabolic pathways.

Low-intensity exercise induces acute shifts in liver and skeletal muscle substrate metabolism but not chronic adaptations in tissue oxidative capacity.

Adaptations in hepatic and skeletal muscle substrate metabolism following acute and chronic (6 wk; 5 days/wk; 1 h/day) low-intensity treadmill exercise were tested in healthy male C57BL/6J mice. Low-intensity exercise maximizes lipid utilization; therefore, we hypothesized pathways involved in lipid metabolism would be most robustly affected. Acute exercise nearly depleted liver glycogen immediately postexercise (0 h), whereas hepatic triglyceride (TAG) stores increased in the early stages after exercise (0-3 h).

Hydrogen Bonding Phase-Transfer Catalysis with Potassium Fluoride: Enantioselective Synthesis of β-Fluoroamines.

Potassium fluoride (KF) is an ideal reagent for fluorination because it is safe, easy to handle and low-cost. However, poor solubility in organic solvents coupled with limited strategies to control its reactivity has discouraged its use for asymmetric C-F bond formation. Here, we demonstrate that hydrogen bonding phase-transfer catalysis with KF provides access to valuable β-fluoroamines in high yields and enantioselectivities.

Asymmetric nucleophilic fluorination under hydrogen bonding phase-transfer catalysis.

Common anionic nucleophiles such as those derived from inorganic salts have not been used for enantioselective catalysis because of their insolubility. Here, we report that merging hydrogen bonding and phase-transfer catalysis provides an effective mode of activation for nucleophiles that are insoluble in organic solvents. This catalytic manifold relies on hydrogen bonding complexation to render nucleophiles soluble and reactive, while simultaneously inducing asymmetry in the ensuing transformation.

Mechanisms for C(sp)-Si activation of aryltrimethylsilyl groups in palladium-catalysed couplings.

Silyl-substituted aromatic compounds can participate as the electrophilic component in palladium-catalysed cross-couplings, and reactivity is enhanced by a neighbouring silyl-group. Products analogous to those obtained from C-H activation chemistry are accessible by this means with the additional benefit of regiochemistry defined by the site of silyl substitution. DFT studies described here show that the mechanism of C-Si cleavage is distinct from previously recognised mechanisms for C-H cleavage, with a cascade of silyl intermediates en route to a stable product.

Hydrogen-Bonded Homoleptic Fluoride-Diarylurea Complexes: Structure, Reactivity, and Coordinating Power.

Hydrogen bonding with fluoride is a key interaction encountered when analyzing the mode of action of 5'-fluoro-5'-deoxyadenosine synthase, the only known enzyme capable of catalyzing the formation of a C-F bond from F. Further understanding of the effect of hydrogen bonding on the structure and reactivity of complexed fluoride is therefore important for catalysis and numerous other applications, such as anion supramolecular chemistry. Herein we disclose a detailed study examining the structure of 18 novel urea-fluoride complexes in the solid state, by X-ray and neutron diffraction, and in solution phase and explore the reactivity of these complexes as a fluoride source in S2 chemistry.

Palladium-catalysed directed C-H activation by anilides and ureas; water participation in a general base mechanism.

C-H activation plays a central role in organometallic catalysis. Concerted metallation-deprotonation (CMD) has been dominant as the pathway for C-H bond cleavage. In the course of studying the mechanism of C-H activation of arylamides and arylureas with Pd complexes as part of catalytic oxidative Heck reactions, DFT calculations were carried out.

Coordination diversity in hydrogen-bonded homoleptic fluoride-alcohol complexes modulates reactivity.

The nucleophilic reactivity of fluoride ion is altered in the presence of hydrogen-bond donors, including alcohols. Relatively little is known about the coordination involved; to rectify this, the X-ray structures of fourteen novel fluoride-alcohol complexes with tetrabutylammonium as the counterion have been determined. The coordination number varies from two to four depending on the steric bulk of the alcohol and is closely linked to trends in reactivity.

Health Status After Transcatheter or Surgical Aortic Valve Replacement in Patients With Severe Aortic Stenosis at Increased Surgical Risk: Results From the CoreValve US Pivotal Trial.

Objectives: This study sought to compare the health status outcomes for patients treated with either self-expanding transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (AVR).

Background: In patients at increased surgical risk, TAVR with a self-expanding bioprosthesis is associated with improved 1-year survival compared with AVR. However, elderly patients may be just as concerned with quality-of-life improvement as with prolonged survival as a goal of treatment.

Origins of observed reactivity and specificity in the addition of B2Cl4 and analogues to unsaturated compounds.

In 1954 Schlesinger and co-workers observed the direct reaction of diboron tetrachloride with simple organic compounds under mild conditions, the 1,2 addition product being formed with either ethylene or acetylene. In the following 25 years a series of addition reactions to simple alkenes, alkynes and dienes was demonstrated. B2F4 was shown to react in similar manner, albeit under more forcing conditions.

Quinap and congeners: atropos PN ligands for asymmetric catalysis.

Among the range of P,N-chelating ligands that have been employed in asymmetric catalysis, those relying on atropisomerism for the stability of individual enantiomers form a definable class. These APN (atropos P,N) ligands require a specific type of biaryl, with one component carrying a pendant phosphine unit, most commonly diaryl substituted, and the other bearing an sp(2)-nitrogen adjacent to the biaryl link. When substituents in the biaryl inhibit rotation about the linking bond, stable nonracemizing six-membered ring chelates can be formed.

cis-Specific hydrofluorination of alkenylarenes under palladium catalysis through an ionic pathway.

This paper describes the hydrofluorination of alkenes through sequential H(-) and F(+) addition under palladium catalysis. The reaction is cis specific, thus providing access to benzylic fluorides. The mechanism of this reaction involves an ionic pathway and is distinct from known hydrofluorinations involving radical intermediates.

Oxidative addition to palladium(0) diphosphine complexes: observations of mechanistic complexity with iodobenzene as reactant.

Using a combination of electrochemical and NMR techniques, the oxidative addition of PhX to three closely related bis-diphosphine P2Pd(0) complexes, where the steric bulk of just one substituent was varied, has been analysed quantitatively. For the complex derived from MetBu2P, a rapid reaction ensued with PhI following an associative mechanism, and data was also obtained by cyclic voltammetry for PhOTs, PhBr and PhCl, revealing distinct relative reactivities from the related (PCx3)2Pd complex (Cx = cyclohexyl) previously studied. The corresponding EttBu2P complex reacted more slowly with PhI and was studied by NMR spectroscopy.

Reactive intermediates in catalytic alkenylation; pathways for Mizoroki-Heck, oxidative Heck and Fujiwara-Moritani reactions.

Several closely related palladium-catalysed reactions involve the addition of Pd-C across an alkene, and subsequent β-elimination of Pd-H to give a more substituted alkene. The Pd-C precursor, normally possessing an sp(2) carbon bound to palladium, can be formed in several different ways, leading to sub-classes of reaction based on a common principle and convergent outcomes. The reaction pathway can vary from simple to highly subtle depending on the nature of the reactants and the ligation of the catalyst.

Meta-analysis in asymmetric catalysis. Influence of chelate geometry on the roles of PN chelating ligands.

All X-ray structures of PN ligands forming 6-ring metal complex chelates have been retrieved from the CDS database, and those lacking chelate chirality filtered out. Many of the remainder fit naturally into four main families (PPFA, FcPhox, Phox and Quinap), which have been widely applied to asymmetric catalysis in diverse ways. It is known through experimental observation that certain of these ligand structures are more effective for specific classes of reaction but there has been little by way of explanation for their divergent behaviour.

Dinuclear palladium complexes--precursors or catalysts?

Calculations help: Recent work from Schoenebeck's group has demonstrated beyond reasonable doubt that the dimeric LPd(I) Br catalysts that are widely used in coupling chemistry operate through prior formal reduction to an LPd(0) species. Conversely, L(2)Pd(0) catalysts can be activated by oxidation. In other cases a binuclear species can persist through the catalytic cycle.

Palladium-catalyzed substitution and cross-coupling of benzylic fluorides.

Benzylic fluorides are suitable substrates for Pd(0)-catalyzed Tsuji-Trost substitution using carbon, nitrogen, oxygen, and sulfur nucleophiles and for cross-coupling with phenylboronic acid. For the bifunctional substrate 4-chlorobenzyl fluoride, fine-tuning of the reaction conditions allows for the regioselective displacement of either the chlorine or fluorine substituent. The leaving group ability of fluoride vs other groups displaced in substitution is CF(3)CO(2) ≈ p-NO(2)C(6)H(4)CO(2) ≈ OCO(2)CH(3) > F > CH(3)CO(2), a ranking similar to allylic fluorides under Pd catalysis.

Implementation of a comprehensive blood conservation program can reduce blood use in a community cardiac surgery program.

Objective: The study objective was to determine the effects of implementing a blood conservation algorithm on blood product use and outcomes in a community cardiac surgery program.

Methods: A blood management strategy including lower hemoglobin transfusion threshold and algorithm-driven decisions was adopted. Intraoperatively, point-of-care testing was used to avoid inappropriate component transfusion.

Unusual inverse temperature dependence on reaction rate in the asymmetric autocatalytic alkylation of pyrimidyl aldehydes.

Observations of an intriguing inverse temperature dependence on reaction rate and a profound induction period in the Soai autocatalytic reaction are reported along with detailed kinetic and NMR investigations of the product alkoxide at low temperatures, leading to the suggestion that the active catalyst is derived in situ from the tetrameric ground state.