Epoxides are useful intermediates for the manufacture of a diverse set of chemical products. Current routes of olefin epoxidation either involve hazardous reagents or generate stoichiometric side products, leading to challenges in separation and significant waste streams. Here, we demonstrate a sustainable and safe route to epoxidize olefin substrates using water as the oxygen atom source at room temperature and ambient pressure. Manganese oxide nanoparticles (NPs) are shown to catalyze cyclooctene epoxidation with Faradaic efficiencies above 30%. Isotopic studies and detailed product analysis reveal an overall reaction in which water and cyclooctene are converted to cyclooctene oxide and hydrogen. Electrokinetic studies provide insights into the mechanism of olefin epoxidation, including an approximate first-order dependence on the substrate and water and a rate-determining step which involves the first electron transfer. We demonstrate that this new route can also achieve a cyclooctene conversion of ∼50% over 4 h.

Understanding the function of nitric oxide (NO), a lipophilic messenger in physiological processes across nervous, cardiovascular and immune systems, is currently impeded by the dearth of tools to deliver this gaseous molecule in situ to specific cells. To address this need, we developed iron sulfide nanoclusters that catalyse NO generation from benign sodium nitrite in the presence of modest electric fields. Locally generated NO activates the NO-sensitive cation channel, transient receptor potential vanilloid family member 1 (TRPV1), and latency of TRPV1-mediated Ca 2+ responses can be controlled by varying the applied voltage. Integrating these electrocatalytic nanoclusters with multimaterial fibres allows NO-mediated neuronal interrogation in vivo . In situ generation of NO within the ventral tegmental area via the electrocatalytic fibres evoked neuronal excitation in the targeted brain region and its excitatory projections. This NO generation platform may advance mechanistic studies of the role of NO in the nervous system and other organs.

Aims  To assess functional tricuspid regurgitation (FTR) determinants, consequences, and independent impact on outcome in degenerative mitral regurgitation (DMR). Methods and results  All patients diagnosed with isolated DMR 2003–2011, with structurally normal tricuspid leaflets, prospective FTR grading and systolic pulmonary artery pressure (sPAP) estimation by Doppler echocardiography at diagnosis were identified and long-term outcome analysed. The 5083 DMR eligible patients [63 ± 16 years, 47% female, ejection fraction (EF) 63 ± 7%, and sPAP 35 ± 13 mmHg] presented with FTR graded trivial in 45%, mild in 37%, moderate in 15%, and severe in 3%. While pulmonary hypertension (PHTN-sPAP ≥ 50 mmHg) was the most powerful FTR severity determinant, other strong FTR determinants were older age, female sex, lower left ventricle EF, DMR, and particularly atrial fibrillation (AFib) (all P ≤ 0.002). Functional tricuspid regurgitation moderate/severe was independently linked to more severe clinical presentation, more oedema, lower stroke volume, and impaired renal function (P ≤ 0.01). Survival (95% confidence interval) throughout follow-up [70% (69–72%) at 10 years] was strongly associated with FTR severity [82% (80–84%) for trivial, 69% (66–71%) for mild, 51% (47–57%) for moderate, and 26% (19–35%) for severe, P < 0.0001]. Excess mortality persisted after comprehensive adjustment [adjusted hazard ratio 1.40 (1.18–1.67) for moderate FTR and 2.10 (1.63–2.70) for severe FTR, P ≤ 0.01]. Excess mortality persisted adjusting for sPAP/right ventricular function (P < 0.0001), by matching [adjusted hazard ratios 2.08 (1.50–2.89), P < 0.0001] and vs. expected survival [risk ratio 1.79 (1.48–2.16), P < 0.0001]. Within 5-year of diagnosis valve surgery was performed in 73% (70–75%) and 15% (13–17%) of severe and moderate DMR and in only 26% (19–34%) and 6% (4–8%) of severe and moderate FTR. Valvular surgery improved outcome without alleviating completely higher mortality associated with FTR (P < 0.0001). Conclusion  In this large DMR cohort, FTR was frequent and causally, not only linked to PHTN but also to other factors, particularly AFib. Higher FTR severity is associated at diagnosis with more severe clinical presentation. Long term, FTR is independently of all confounders, associated with considerably worse mortality. Functional tricuspid regurgitation moderate and even severe is profoundly undertreated. Thus careful assessment, consideration for tricuspid surgery, and testing of new transcatheter therapy is warranted.

Lactones serve as key synthetic intermediates for the large-scale production of several important chemicals, such as polymers, pharmaceuticals, and scents. Current thermochemical methods for the formation of some lactones rely on molecular oxidants, which yield stoichiometric side products that result in a poor atom economy and impose safety hazards when in contact with organic substrates and solvents. Electrochemical synthesis can alleviate these concerns by exploiting an applied potential to enable the possibility of a clean and safe route for lactonization. In this study, we investigated the mechanism of electrochemical lactone formation from cyclic ketones. When using a platinum anode and cathode in acetonitrile with 10 M H 2 O and 400 mM cyclohexanone, we found that non-Baeyer−Villiger products, δhexanolactone and γ-caprolactone, are formed with a total Faradaic efficiency of ∼20%. Isotope labeling experiments support that water is the oxygen atom source for this reaction. In addition, electrochemical kinetic data suggest a first-order dependence on water at low water concentrations (<2 M H 2 O) and a zeroth order dependence on the substrate, cyclohexanone. A Tafel slope of 139 mV/decade was measured at 400 mM cyclohexanone and 10 M H 2 O, implying an initial electron transfer as the ratedetermining step. Literature-proposed mechanisms for similar transformations suggest an outer-sphere pathway. However, on the basis of the collected electrochemical kinetic data, we propose the possibility that Pt reacts with water in an initial electron transfer that forms Pt−OH, which can subsequently react with the ketone substrate. A subsequent electron transfer forms a ring-opened carboxylic acid cation that can reclose to form either of the observed fiveor six-membered ring lactone products.

Lactones serve as key synthetic intermediates for the large-scale production of several important chemicals, such as polymers, pharmaceuticals, and scents. Current thermochemical methods for the formation of some lactones rely on molecular oxidants, which yield stoichiometric side products that result in a poor atom economy and impose safety hazards when in contact with organic substrates and solvents. Electrochemical synthesis can alleviate these concerns by exploiting an applied potential to enable the possibility of a clean and safe route for lactonization. In this study, we investigated the mechanism of electrochemical lactone formation from cyclic ketones. When using a platinum anode and cathode in acetonitrile with 10 M H2O and 400 mM cyclohexanone, we found that non-Baeyer-Villiger products, δ-hexanolactone and ɣ-caprolactone, are formed with a total Faradaic efficiency of ~20%. Isotope labeling experiments support that water is the oxygen atom source for this reaction. In addition, electrochemical kinetic data suggest a 1st order dependence on water at low water concentrations (<2 M H2O) and a 0th order dependence on the substrate, cyclohexanone. A Tafel slope of 139 mV/decade was measured at 400 mM cyclohexanone and 10 M H2O, implying an initial electron transfer as the rate determining step. Literature proposed mechanisms for similar transformations suggest an outer sphere pathway. However, based on the collected electrochemical kinetic data, we propose the possibility that Pt reacts with water in an initial electron transfer that forms Pt-OH, which can subsequently react with the ketone substrate. A subsequent electron transfer forms a ring opened carboxylic acid cation that can reclose to form either of the observed five- or six-member ring lactone products.