Predictive control of selective secondary alcohol oxidation of glycerol on NiOOH.

Many biomass intermediates are polyols and selectively oxidizing only a primary or secondary alcohol group is beneficial for the valorization of these intermediates. For example, production of 1,3-dihydroxyacetone, a highly valuable oxidation product of glycerol, requires selective secondary alcohol oxidation. However, selective secondary alcohol oxidation is challenging due to its steric disadvantage. This study demonstrates that NiOOH, which oxidizes alcohols via two dehydrogenation mechanisms, hydrogen atom transfer and hydride transfer, can convert glycerol to 1,3-dihydroxyacetone with high selectivity when the conditions are controlled to promote hydrogen atom transfer, favoring secondary alcohol oxidation. This rational production of 1,3-dihydroxyacetone achieved by selectively enabling one desired dehydrogenation pathway, without requiring alteration of catalyst composition, demonstrates how comprehensive mechanistic understanding can enable predictive control over selectivity.

Electrochemical Dehydrogenation Pathways of Amines to Nitriles on NiOOH.

Nitriles are highly important synthetic intermediates with applications in a wide variety of organic reactions including production of pharmaceuticals, fine chemicals, and agricultural chemicals. Thus, developing effective green routes to oxidize amines to nitriles is of great interest. One promising method to achieve the oxidation of primary amines to nitriles is through electrochemical oxidation on NiOOH electrodes. This reaction has long been thought to occur through an indirect mechanism consisting of a series of potential independent hydrogen atom transfer steps to catalytic Ni3+ sites in NiOOH, which reduces NiOOH to Ni(OH)2. The role of the applied potential in this mechanism is simply to regenerate NiOOH by oxidizing Ni(OH)2. In this work, we demonstrate that a second, potential-dependent pathway recently found to apply to alcohol and aldehyde oxidation on NiOOH and consisting of potential-dependent hydride transfer to Ni4+ sites is the dominant pathway for the oxidation of amines using propylamine and benzylamine as model systems. After qualitatively and quantitatively examining the contributions of indirect and potential-dependent oxidation pathways to amine oxidation on NiOOH, we also examine the effect the amine concentration, solution pH, applied bias, and deuterium substitution have on the two pathways, further clarifying their mechanisms and exploring what factors control their rate. This work provides a comprehensive understanding of the mechanism of primary amine oxidation on NiOOH.

Mechanistic Differences between Electrochemical Hydrogenation and Hydrogenolysis of 5-Hydroxymethylfurfural and Their pH Dependence.

Hydrogenation and hydrogenolysis are two important reactions for electrochemical reductive valorization of biomass-derived oxygenates such as 5-hydroxymethylfurfural (HMF). In general, hydrogenolysis (which combines hydrogenation and deoxygenation) is more challenging than hydrogenation (which does not involve the cleavage of carbon-oxygen bonds). Thus, identifying factors and conditions that can promote hydrogenolysis is of great interest for reductive valorization of biomass-derived oxygenates. For the electrochemical reduction of HMF and its derivatives, it is known that aldehyde hydrogenation is not a part of aldehyde hydrogenolysis but rather a competing reaction; however, no atomic-level understanding is currently available to explain their electrochemical mechanistic differences. In this study, combined experimental and computational investigations were performed using Cu electrodes to elucidate the key mechanistic differences between electrochemical hydrogenation and hydrogenolysis of HMF. The results revealed that hydrogenation and hydrogenolysis of HMF involve the formation of different surface-adsorbed intermediates via different reduction mechanisms and that lowering the pH promoted the formation of the intermediates required for aldehyde and alcohol hydrogenolysis. This study for the first time explains the origins of the experimentally observed pH-dependent selectivities for hydrogenation and hydrogenolysis and offers a new mechanistic foundation upon which rational strategies to control electrochemical hydrogenation and hydrogenolysis can be developed.

Electrochemical Oxidation of HMF via Hydrogen Atom Transfer and Hydride Transfer on NiOOH and the Impact of NiOOH Composition.

A great deal of attention has been directed toward studying the electrochemical oxidation of 5-hydroxymethylfurfural (HMF), a molecule that can be obtained from biomass-derived cellulose and hemicellulose, to 2,5-furandicarboxylic acid (FDCA), a molecule that can replace the petroleum-derived terephthalic acid in the production of widely used polymers such as polyethylene terephthalate. NiOOH is one of the best and most well studied electrocatalysts for achieving this transformation; however, the mechanism by which it does so is still poorly understood. This study quantitatively examines how two different dehydrogenation mechanisms on NiOOH impact the oxidation of HMF and its oxidation intermediates on the way to FDCA. The first mechanism is a well-established indirect oxidation mechanism featuring chemical hydrogen atom transfer to Ni3+ sites while the second mechanism is a newly discovered potential-dependent (PD) oxidation mechanism involving electrochemically induced hydride transfer to Ni4+ sites. The composition of NiOOH was also tuned to shift the potential of the Ni(OH)2 /NiOOH redox couple and to investigate how this affects the rates of indirect and PD oxidation as well as intermediate accumulation during a constant potential electrolysis. The new insights gained by this study will allow for the rational design of more efficient electrochemical dehydrogenation catalysts.

Inhaled pulmonary vasodilators are not associated with improved gas exchange in mechanically ventilated patients with COVID-19: A retrospective cohort study.

PURPOSE: Measure the effect of inhaled pulmonary vasodilators on gas exchange in mechanically ventilated patients with COVID-19. METHODS: A retrospective observational cohort study at three New York University Hospitals was performed including eighty-four mechanically ventilated SARS Cov-2 nasopharyngeal PCR positive patients, sixty nine treated with inhaled nitric oxide (iNO) and fifteen with inhaled epoprostenol (iEPO). The primary outcomes were change in PAO2:FIO2 ratio, oxygenation Index (OI), and ventilatory ratio (VR) after initiation of inhaled pulmonary vasodilators. RESULTS: There was no significant change in PAO2:FIO2ratio after initiation of iNO (mean - 4.1, 95% CI -17.3-9.0, P = 0.54) or iEPO (mean - 3.4, 95% CI -19.7-12.9, P = 0.66), in OI after initiation of iNO (mean 2.1, 95% CI-0.04-4.2, P = 0.054) or iEPO (mean - 3.4, 95% CI -19.7-12.9, P = 0.75), or in VR after initiation of iNO (mean 0.17, 95% CI -0.03-0.36, P = 0.25) or iEPO (mean 0.33, 95% CI -0.0847-0.74, P = 0.11). PAO2:FIO2, OI and VR did not significantly change over a five day period starting the day prior to drug initiation in patients who received either iNO or iEPO assessed with a fixed effects model. CONCLUSION: Inhaled pulmonary vasodilators were not associated with significant improvement in gas exchange in mechanically ventilated patients with COVID-19.

The Impact of 5-Hydroxymethylfurfural (HMF)-Metal Interactions on the Electrochemical Reduction Pathways of HMF on Various Metal Electrodes.

5-Hydroxymethylfurfural (HMF), which can be derived from lignocellulosic biomass, is an important platform molecule that can be used to produce valuable biofuels and polymeric materials. Electrochemical reduction of HMF is of great interest as it uses water as the hydrogen source and achieves desired reduction reactions at room temperature and ambient pressure. Hydrogenation and hydrogenolysis are two important reactions for reductive HMF conversion. Therefore, elucidating key characteristics of electrocatalysts that govern the selectivity for hydrogenation and hydrogenolysis is critical in rationally developing efficient and selective electrocatalysts. In this study, combined experimental and computational investigations are used to demonstrate how the adsorption energy of HMF on metal surfaces and the resulting changes in the intramolecular bond lengths of adsorbed HMF directly impact the reduction pathways of HMF. These results make it possible to rationally understand a general trend in the behaviors observed when using various metal electrodes for HMF reduction.

Unraveling Two Pathways for Electrochemical Alcohol and Aldehyde Oxidation on NiOOH.

Selective oxidation of alcohols to their corresponding aldehyde or carboxylic acid is one of the most important classes of organic synthesis reactions. In addition, electrochemical alcohol oxidation is considered a viable anode reaction that can be paired with H2 evolution or other reductive fuel production reactions in electrochemical and photoelectrochemical cells. NiOOH, a material that has been extensively studied as an oxygen evolution catalyst, is among the most promising electrocatalysts for selective alcohol oxidation. Electrochemical alcohol oxidation by NiOOH has been understood since the 1970s to proceed through a hydrogen atom transfer to NiOOH. In this study, we establish that there is a second, more dominant general alcohol oxidation pathway on NiOOH enabled at more positive potentials. Using a three-step electrochemical procedure we developed, we deconvoluted the currents corresponding to these two pathways for various alcohols and aldehydes. The results show that alcohols and aldehydes have a distinct difference in their respective preferences for the two oxidation pathways. Our three-step electrochemical procedure also allowed us to evaluate the Ni valence involved with the different oxidation pathways to elucidate their mechanistic differences. Using these experimental results coupled with a computational investigation, we propose that the new pathway entails hydride transfer from the substrate to Ni4+ sites in NiOOH. This study offers an essential foundation to understand various oxidative electrochemical dehydrogenation reactions on oxide and hydroxide-based catalytic electrodes.

Synthesis, Characterization, and Nanomaterials Generated from 6,6'-(((2-Hydroxyethyl)azanediyl)bis(methylene))bis(2,4-di- tert-butylphenol) Modified Group 4 Metal Alkoxides.

The impact on the morphology nanoceramic materials generated from group 4 metal alkoxides ([M(OR)4]) and the same precursors modified by 6,6'-(((2-hydroxyethyl)azanediyl)bis(methylene))bis(2,4-di- tert-butylphenol) (referred to as H3-AM-DBP2 (1)) was explored. The products isolated from the 1:1 stoichiometric reaction of a series of [M(OR)4] where M = Ti, Zr, or Hf; OR = OCH(CH3)2(OPr i); OC(CH3)3(OBu t); OCH2C(CH3)3(ONep) with H3-AM-DBP2 proved, by single crystal X-ray diffraction, to be [(ONep)Ti( k4( O,O',O'',N)-AM-DBP2)] (2), [(OR)M(µ( O)- k3( O',O'',N)-AM-DBP2)]2 [M = Zr: OR = OPr i, 3·tol; OBu t, 4·tol; ONep, 5·tol; M = Hf: OR = OBu t, 6·tol; ONep, 7·tol]. The product from each system led to a tetradentate AM-DBP2 ligand and retention of a parent alkoxide ligand. For the monomeric Ti derivative (2), the metal was solved in a trigonal bipyramidal geometry, whereas for the Zr (3-5) and Hf (6, 7) derivatives a symmetric dinuclear complex was formed where the ethoxide moiety of the AM-DBP2 ligand bridges to the other metal center, generating an octahedral geometry. High quality density functional theory level gas-phase electronic structure calculations on compounds 2-7 using Gaussian 09 were used for meaningful time dependent density functional theory calculations in the interpretation of the UV-vis absorbance spectral data on 2-7. Nanoparticles generated from the solvothermal treatment of the ONep/AM-DBP2 modified compounds (2, 5, 7) in comparison to their parent [M(ONep)4] were larger and had improved regularity and dispersion of the final ceramic nanomaterials.

Principles of Antibiotic Management of Community-Acquired Pneumonia.

Community-acquired pneumonia (CAP) encompasses a broad spectrum of disease severity and may require outpatient, inpatient, or intensive care management. Successful treatment hinges on expedient delivery of appropriate antibiotic therapy tailored to both the likely offending pathogens and the severity of disease. This review summarizes key principles in starting treatment and provides recommended empiric therapy regimens for each site of care. In addition, we discuss the antimicrobial and anti-inflammatory role macrolides play in CAP, as well as specific information for managing individual CAP pathogens such as community-acquired methicillin-resistant Staphylococcus aureus and drug-resistant Streptococcus pneumoniae. We also examine several novel antibiotics being developed for CAP and review the evidence guiding duration of therapy and current best practices for the transition of hospitalized patients from intravenous antibiotics to oral therapy.

Improving outcomes in community-acquired pneumonia.

PURPOSE OF REVIEW: Community-acquired pneumonia (CAP) is a pervasive disease that is encountered in outpatient and inpatient settings. CAP is the leading cause of death from an infectious disease and accounts for significant worldwide morbidity and mortality. This update reviews current advances that can be used to promote improved outcomes in CAP. RECENT FINDINGS: Early recognition of CAP and its severe presentations, with appropriate site of care decisions, leads to reduced patient mortality. In addition to traditional prognostic tools, certain serum biomarkers can assist in defining disease severity and guide treatment and management strategies. The use of macrolides as part of combination antibiotic therapy has shown beneficial mortality effects across the CAP disease spectrum, especially for those with severe illness. When treating community-associated, methicillin-resistant Staphylococcus aureus pneumonia, use of an antitoxin antibiotic is likely to be valuable. Adjunctive therapy with corticosteroids may prevent delayed clinical resolution in selected patients with severe CAP. Recent data expand on the interaction of CAP with comorbid disease, particularly cardiovascular disease, and its impact on mortality in CAP patients. SUMMARY: Improved diagnostic tools, optimized treatment regimens, and enhanced understanding of CAP-induced perturbations in comorbid disease states hold promise to improve patient outcomes.