Light-Driven Enantioselective Carbene-Catalyzed Radical-Radical Coupling.

An enantioselective carbene-catalyzed radical-radical coupling of acyl imidazoles and racemic Hantzsch esters is disclosed. This method involves the coupling of an N-heterocyclic carbene-derived ketyl radical and a secondary sp3 -carbon radical and allows access to chiral α-aryl aliphatic ketones in moderate-to-good yields and enantioselectivities without any competitive epimerization. The utility of this protocol is highlighted by the late-stage functionalization of various pharmaceutical compounds and is further demonstrated by the transformation of the enantioenriched products to biologically relevant molecules. Computational investigations reveal the N-heterocyclic carbene controls the double-facial selectivity of the ketyl radical and the alkyl radicals, respectively.

Enantioselective Copper-Catalyzed Borylative Amidation of Allenes.

An approach for the copper-catalyzed synthesis of enantioenriched amides bearing an α-stereogenic center is disclosed. This method involves the addition of an allyl copper species to an isocyanate and allows access to α-substituted chiral amides in high yields and high-to-excellent enantioselectivities. The utility of α-vinyl ß-boryl amides in synthesis is highlighted by the diversification of products to afford highly useful scaffolds. DFT calculations reveal that the catalyst preferentially coordinates to the oxygen of the isocyanate. Enantiocontrol arises from the steric repulsion between the boryl group and the stereodirecting phenyl of the chiral ligand.

Alternative access for transcatheter aortic valve replacement in older adults: A collaborative study from France and United States.

BACKGROUND: We examined the outcomes of older adults undergoing nontrans-femoral (non-TF) transcatheter aortic valve replacement (TAVR) procedures including trans-apical (TA), trans-aortic (TAo), trans-subclavian (TSub), and trans-carotid (TCa) techniques. METHODS AND RESULTS: This is an observational study of all consecutive older patients who underwent non-TF TAVR for symptomatic severe AS with Edwards Sapien (ES), Medtronic CoreValve, ES3 or Lotus Valve at three centers in France and the United States from 04/2008 to 02/2017. Baseline characteristics and clinical outcomes were defined according to VARC-2 criteria. Of 857 patients who received TAVR, 172 (20%) had an alternative access procedure. Of these, 45 (26%) were TA, 67 (39%) TAo, 17 (10%) TSub, and 43 (25%) TCa procedures. The preference for non-TF access site was different between the two countries (US: TA 39%, TAo 52%, TSub 9%; TCa 0% vs. France: TA 9%, TAo 23%, TSub 11%, and TCa 57%, P-value < .001). Most patients who underwent TAo TAVR were older women (median age: TA 82, TAo 84, TSub 81, TCa 81, P-value = 0.043; female gender: TA 32 (27%), TAo 30 (55%), TSub 10 (41%), TCa 27 (37%), P-value = .021). The predicted Society of Thoracic Surgery risk of mortality was similar among groups (TA 7%, TAo 7%, TSub 6%, TCa 7%, P-value= .738). No differences were observed in the frequency of para-valvular leak, intra-procedural bleeding, vascular complications, conversion to open-heart surgery, or development of acute kidney injury. The highest in-hospital mortality was observed in the TAo group (TA 2%, TAo 15%, TSub 0%, TCa 2%, P-value = .014). However, hospital length of stay, one-month, and one-year mortality were similar among non-TF techniques. CONCLUSION: Although regional differences exist in the choice of alternative access techniques, centers with high technical expertise can provide a safe alternative to traditional TF TAVR. TAo TAVR was associated with higher in-hospital mortality than other non-TF approaches, and this may have reflected patient rather than procedural factors. All alternative access techniques had similar mortality rates and clinical outcomes at one-year follow-up. Trans-carotid access is safe and feasible compared to other non-TF access techniques.

D-A-D-type narrow-bandgap small-molecule photovoltaic donors: pre-synthesis virtual screening using density functional theory.

A new series of D-A-D-type small-molecule photovoltaic donors are designed and virtually screened before synthesis using time-dependent density functional theory calculations carefully validated against various polymeric and molecular donors. In this series of new design, benzodithiophene is kept as D to achieve the optimum highest-occupied molecular orbital energy level, while thienopyrroledione is initially chosen as A but later replaced by difluorinated benzodiathiazole or its selenide derivative to achieve the optimum band gap. The D-A-D core is end-capped by pyridone units which could not only enhance their self-assembly via hydrogen bonds but also play a role as an acceptor (A') to form an extended A'-D-A-D-A' small-molecule donor.

Direct Observation of Confinement Effects of Semiconducting Polymers in Polymer Blend Electronic Systems.

The advent of special types of polymeric semiconductors, known as "polymer blends," presents new opportunities for the development of next-generation electronics based on these semiconductors' versatile functionalities in device applications. Although these polymer blends contain semiconducting polymers (SPs) mixed with a considerably high content of insulating polymers, few of these blends unexpectedly yield much higher charge carrier mobilities than those of pure SPs. However, the origin of such an enhancement has remained unclear owing to a lack of cases exhibiting definite improvements in charge carrier mobility, and the limited knowledge concerning the underlying mechanism thereof. In this study, the morphological changes and internal nanostructures of polymer blends based on various SP types with different intermolecular interactions in an insulating polystyrene matrix are investigated. Through this investigation, the physical confinement of donor-acceptor type SP chains in a continuous nanoscale network structure surrounded by polystyrenes is shown to induce structural ordering with more straight edge-on stacked SP chains. Hereby, high-performance and transparent organic field-effect transistors with a hole mobility of ≈5.4 cm2 V-1 s-1 and an average transmittance exceeding 72% in the visible range are achieved.

Extended-release acetylsalicylic acid for secondary prevention of stroke and cardiovascular events.

INTRODUCTION: Aspirin has been the bedrock of antiplatelet treatment strategies for the secondary prevention of recurrent cardiovascular and cerebrovascular events for the last 3 decades. The limitations of standard aspirin therapy include bleeding, gastrotoxicity, and loss of antiplatelet effect over a 24-hour period in selected high-risk patients. An extended-release (ER) aspirin formulation, Durlaza® (New Haven Pharmaceuticals, Inc., North Haven, CT), has been developed to address some of the latter limitations and may provide an alternative to standard aspirin in the secondary prevention of cardiovascular disease. AREAS COVERED: We searched articles describing the use aspirin for secondary prevention of stroke and cardiovascular events in PubMed published until May 2016. This is a comprehensive review which describes active- and placebo-controlled clinical trials, overview of American and European recommendations, controversies surrounding standard aspirin use, and a description of pharmacodynamics of standard and extended release aspirin formulations. Expert commentary: Available data indicates an increased bleeding risk with the use of standard aspirin therapy in conjunction with potent P2Y12 receptor blockers, and/or oral anticoagulants. Trials evaluating the efficacy of replacing aspirin with a low-dose oral anticoagulant in patients with stable cardiovascular disease or acute coronary syndrome are ongoing. Future studies are warranted to determine if the use of ER-ASA formulation may obviate safety concerns surrounding standard aspirin therapy.