Efficient carbene transfer reactivity mediated by Fe(II) complexes supported by bulky alkoxides.

Herein we describe the stoichiometric and catalytic carbene-transfer reactivity of iron(II) alkoxide complexes with iodonium ylide precursors. Treatment of PhIC(CO2Me)2 with styrene in the presence of catalytic amounts of several different Fe(OR)2(THF)2 precursors results in efficient cyclopropanation for a variety of styrenes. Computational and reactivity studies suggest a novel remote metallocarbene/vinyl radical intermediate, Fe(OR)2(κ2-(OC(OMe))2C), which could be responsible for the reactive nature of the catalyst.

Combining [MoVIO3] and [M0(CO)3] (M = Mo, Cr) Fragments within the Same Complex: Synthesis and Reactivity of the Single Oxo-Bridged Heterobimetallics Supported by Xanthene-Based Heterodinucleating Ligands.

A functional model of Mo-Cu carbon monoxide dehydrogenase (CODH) enzyme requires the presence of an oxidant (metal-oxo) and a metal-bound carbonyl in close proximity. In this work, we report the synthesis, characterization, and reactivity of a heterobimetallic complex combining Mo(VI) trioxo with Mo(0) tricarbonyl. The formation of the heterobimetallic complex is facilitated by the xanthene-bridged heterodinucleating ligand containing a hard catecholate chelate and a soft iminopyridine chelate. A catechol-coordinated square-pyramidal [MoVIO3] fragment interacts directly with the iminopyridine-bound [Mo0(CO)3] fragment via a single (oxo) bridge, with the overall disposition being related to the proposed first step in the CODH mechanism, where square-pyramidal [MoVIO2S] interacts with the [Cu-CO] via a single sulfido bridge. Our attempt to obtain a sulfido-bridged analogue (using [MoO3S]2- precursor) led to a mixture of products possibly containing different (oxo and sulfido) bridges. Despite a direct interaction between Mo(VI) and Mo(0) segments, no internal redox is observed, with the high lying occupied MOs being mostly d-π orbitals at Mo0(CO)3 and the low lying unoccupied MOs being d-π orbitals at MoVIO3. Due to the overall rigid structure, the heterobimetallic complex was found to be stable up to 100 °C in DMF-d7 (based on 1H NMR). The decomposition of the complex above this temperature does not produce CO2 (based on gas chromatography), dissociating stable Mo(CO)3(DMF)3 instead (based on IR). We also synthesized and studied the reactivity of the Mo(VI)/Cr(0) analogue. While this complex demonstrated more facile decomposition, no CO2 production was observed. Density functional theory calculations suggest that the formation of [CO2]2- and its subsequent reductive elimination is endergonic in the present system, likely due to the stability of fac-Mo0(CO)3 and the relative nucleophilic character of the carbonyl carbon engendered by back donation from Mo(0). The calculations also indicate that the replacement of one oxo by sulfido (both terminal and bridging), replacement of catechol with dithiolene, and replacement of Mo(0) with Cr(0) does not affect significantly the energetics of the process, likely requiring the use a less stable and less π-basic CO anchor.

Regioselective Direct C-H Bond Heteroarylation of Thiazoles Enabled by an Iminopyridine-Based α-Diimine Nickel(II) Complex Evaluated by DFT Studies.

Direct C-H bond arylation is a highly effective method for synthesizing arylated heteroaromatics. This method reduces the number of synthetic steps and minimizes the formation of impurities. We report an air- and moisture-stable iminopyridine-based α-diimine nickel(II) complex for direct C5-H bond arylation of thiazole derivatives. Under a low catalyst loading and performing the reactions at lower temperatures (80 °C) under aerobic conditions, we produced mono- and diarylated thiazole units. Competition experiments and density functional theory calculations revealed that the mechanism of C-H activation in 4-methylthiazole involves an electrophilic aromatic substitution.

A circular economy approach to drinking water treatment residue management in a catchment impacted by historic metal mines.

Drinking water treatment residues (DWTR) from mining areas which remove and contain potentially toxic elements (PTE) could still potentially be used as a soil amendment to restore contaminated sites in the same catchment, thus eliminating waste and reducing the chemical and physical mobility of the pollutants. To assess this restorative and regenerative approach to DWTR management, field and pot trials were established with soils from a historic Pb-Zn mine site in the North East of England, amended with either local DWTR or the nearest available municipal green waste compost (GWC). Soils from the mine site were found to have very low levels of nutrients and very high levels of PTE (Pb and Zn > 13, 000 mg/kg). The perennial grass species Phalaris arundinacea, known for many ecosystem service benefits including soil stabilization, was used throughout this study. The application of the BCR sequential extraction to soils amended with the DWTR in the pot trials found a significant decrease in the bioavailability of Pb and Cu (p < 0.05) after plant growth when compared with an unamended control. The field trial involved 648 pre-grown grass plants planted-out into mine soils amended with either DWTR, GWC or a mixture (MIX) of the two, all at rates of 25-30% w/w. Both amendments and the MIX had significant positive effects on biomass production compared to the unamended control in the following order GWC > MIX > DWTR (p < 0.05). Results of the elemental analysis of biomass from the field trial were generally ambiguous and did not reflect the decreased bioavailability noted in the pot trials using the BCR procedure. Pot trials, however, showed increases in plant growth and decreases in concentrations of Cr, Cu, Pb and Zn in above ground biomass following the application of both amendments. Further work should involve the testing of a mixture of DWTR and other soil amendments to enhance plant growth. The success of these trials should provide confidence for those working in drinking water treatment and catchment management to reuse the waste residues in a circular economy and a sustainable way that could improve water quality over time.

Comparing telehealth to traditional office visits for patient management in the COVID-19 pandemic: A cross-sectional study in a respiratory assessment clinic.

INTRODUCTION: The aim of this study was to examine whether telehealth is as safe and effective as traditional office visits in assessing and treating patients with symptoms consistent with COVID-19. METHODS: In this retrospective cross-sectional study, the primary outcome was any 14-day related healthcare follow-up event(s). Secondary outcomes were the type of 14-day related follow-up event including hospital admission, emergency department visit, office visit, telehealth visit and/or multiple follow-up visits. Individual visit types were identified due to the significant difference between a hospital admission and an office visit. Logistic regressions were done using the predictors of visit type, age, gender and comorbidities and the primary outcome variable of a related follow-up visit and then by follow-up type: hospital admission, emergency department visit or office visit. RESULTS: Of 1305 visits, median age was 42.3 years and 65.8% were female. Traditional office visits accounted for 741 (56.8%) of initial visits, while 564 (43.2%) visits occurred via telehealth. One hundred and forty-six (25.9%) of the telehealth visits resulted in a 14-day related healthcare follow-up visit versus 161 (21.7%) of the office visits (adjusted odds ratio (OR) 1.22, 95% CI 0.94-1.58). DISCUSSION: There was no significant difference in related follow-ups of initial telehealth visits compared to initial office visits including no significant difference in hospital admission or emergency department visits. These findings suggest that based on follow up healthcare utilization, telehealth may be a safe and effective option in assessing and treating patients with respiratory symptoms as the COVID-19 pandemic continues.

Aziridination Reactivity of a Manganese(II) Complex with a Bulky Chelating Bis(Alkoxide) Ligand.

Treatment of Mn(N(SiMe3)2)2(THF)2 with bulky chelating bis(alkoxide) ligand [1,1':4',1''-terphenyl]-2,2''-diylbis(diphenylmethanol) (H2[O-terphenyl-O]Ph) formed a seesaw manganese(II) complex Mn[O-terphenyl-O]Ph(THF)2, characterized by structural, spectroscopic, magnetic, and analytical methods. The reactivity of Mn[O-terphenyl-O]Ph(THF)2 with various nitrene precursors was investigated. No reaction was observed between Mn[O-terphenyl-O]Ph(THF)2 and aryl azides. In contrast, the treatment of Mn[O-terphenyl-O]Ph(THF)2 with iminoiodinane PhINTs (Ts = p-toluenesulfonyl) was consistent with the formation of a metal-nitrene complex. In the presence of styrene, the reaction led to the formation of aziridine. Combining varying ratios of styrene and PhINTs in different solvents with 10 mol% of Mn[O-terphenyl-O]Ph(THF)2 at room temperature produced 2-phenylaziridine in up to a 79% yield. Exploration of the reactivity of Mn[O-terphenyl-O]Ph(THF)2 with various olefins revealed (1) moderate aziridination yields for p-substituted styrenes, irrespective of the electronic nature of the substituent; (2) moderate yield for 1,1'-disubstituted α-methylstyrene; (3) no aziridination for aliphatic α-olefins; (4) complex product mixtures for the ß-substituted styrenes. DFT calculations suggest that iminoiodinane is oxidatively added upon binding to Mn, and the resulting formal imido intermediate has a high-spin Mn(III) center antiferromagnetically coupled to an imidyl radical. This imidyl radical reacts with styrene to form a sextet intermediate that readily reductively eliminates the formation of a sextet Mn(II) aziridine complex.

Cost Analysis of Integrated Behavioral Health in a Large Primary Care Practice.

A residency-based Family Medicine outpatient clinic chose to implement an integrated behavioral health care program in a large primary care clinic in the Southeast to improve patient access to behavioral health care. We hypothesized that embedding a BHP in a primary care setting would be a cost neutral intervention. We implemented a prospective cohort design and included expenses from both inpatient and outpatient visits. We implemented a mixed effects linear regression model to evaluate pre- and post-BHP exposure costs. A total of 1256 patients were identified in the post-BHP exposure period that had more than one-year post-exposure. After applying exclusion criteria, there were 926 patients included in analysis. These patient had an average total cost during the one-year pre-BHP exposure period of $5113 (SD = 7712) and one-year post-BHP exposure period of $5462 (SD = 7813). Our analysis shows a relatively cost neutral impact following the introduction of BHPs in a primary care setting. The results of this study provide a gauge for future planning of services.

Synthesis, electronic structures, and reactivity of mononuclear and dinuclear low-valent molybdenum complexes in iminopyridine and bis(imino)pyridine ligand environments.

Molybdenum in redox non-innocent ligand environments features prominently in biological inorganic systems. While Holm and coworkers, along with many other researchers, have thoroughly investigated formally high-oxidation-state molybdenum (Mo(IV)-Mo(VI)) ligated by dithiolenes, less is known about molybdenum in other formal oxidation states and/or different redox-active ligand environments. This work focuses on the investigation of low-valent molybdenum in four different redox non-innocent nitrogen ligand type environments (mononucleating and dinucleating iminopyridine, mononucleating and dinucleating bis(imino)pyridine). The reaction of iminopyridine N-(2,6-diisopropylphenyl)-1-(pyridin-2-yl)methanimine (L1) with Mo(CO)3(NCMe)3 produced Mo(L1)(CO)3(NCMe). Mo(L1)(CO)3(NCMe) undergoes transformation to Mo(L1)(CO)4 upon treatment with CS2 or prolonged stirring in dichloromethane. The reaction of the open-chain dinucleating bis(iminopyridine) ligand N,N'-(2,7-di-tert-butyl-9,9-dimethyl-9H-xanthene-4,5-diyl)bis(1-(pyridin-2-yl)methanimine) (L2) similarly produced an hexacarbonyl complex Mo2(L2)(CO)6(NCMe)2 which also underwent transformation to the octacarbonyl Mo2(L2)(CO)8. Both complexes featured anti-parallel geometry of the chelating units. The oxidation of Mo(L1)(CO)3(NCMe) with I2 resulted in Mo(L1)(CO)3I2. The reaction of mononucleating potentially tridentate bis(imino)pyridine ligand (L3) (N-mesityl-1-(6-((E)-(mesitylimino)methyl)pyridin-2-yl)methanimine) with both Mo(CO)3(NCMe)3 and Mo(CO)4(NCMe)2 produced complexes Mo(L3)(CO)3(NCMe) and Mo(L3)(CO)4 in which L3 was coordinated in a bidentate fashion, with one imino sidearm unbound. The reaction of dinucleating macrocyclic di(bis(imino)pyridine) analogue (L4) led to the similar chemistry of Mo2(L4)(CO)6(NCMe)2 and Mo2(L4)(CO)8 complexes. Treatment of Mo(L3)(CO)3(NCMe) with I2 formed a mono(carbonyl) complex Mo(L3)(CO)I2 in which molybdenum was formally oxidized and L3 underwent coordination mode change to tridentate. The electronic structures of formally Mo(0) complexes in iminopyridine and bis(imino)pyridine ligand environments were investigated by density functional theory calculations.

Synthesis and Cu(I)/Mo(VI) Reactivity of a Bifunctional Heterodinucleating Ligand on a Xanthene Platform.

In an effort to probe the feasibility of a model of Mo-Cu CODH (CODH = carbon monoxide dehydrogenase) lacking a bridging sulfido group, the new heterodinucleating ligand LH2 was designed and its Cu(I)/Mo(VI) reactivity was investigated. LH2 ((E)-3-(((5-(bis(pyridin-2-ylmethyl)amino)-2,7-di-tert-butyl-9,9-dimethyl-9H-xanthen-4-yl)imino)methyl)benzene-1,2-diol) features two different chelating positions bridged by a xanthene linker: bis(pyridyl)amine for Cu(I) and catecholate for Mo(VI). LH2 was synthesized via the initial protection of one of the amine positions, followed by two consecutive alkylations of the second position, deprotection, and condensation to attach the catechol functionality. LH2 was found to exhibit dynamic cooperativity between two reactive sites mediated by H-bonding of the catechol protons. In the free ligand, catechol protons exhibit H-bonding with imine (intramolecular) and with pyridine (intermolecular in the solid state). The reaction of LH2 with [Cu(NCMe)4]+ led to the tetradentate coordination of Cu(I) via all nitrogen donors of the ligand, including the imine. Cu(I) complexes were characterized by multinuclear NMR spectroscopy, high-resolution mass spectrometry (HRMS), X-ray crystallography, and DFT calculations. Cu(I) coordination to the imine disrupted H-bonding and caused rotation away from the catechol arm. The reaction of the Cu(I) complex [Cu(LH2)]+ with a variety of monodentate ligands X (PPh3, Cl-, SCN-, CN-) released the metal from coordination to the imine, thereby restoring imine H-bonding with the catechol proton. The second catechol proton engages in H-bonding with Cu-X (X = Cl, CN, SCN), which can be intermolecular (XRD) or intramolecular (DFT). The reaction of LH2 with molybdate [MoO4]2- led to incorporation of [MoVIO3] at the catecholate position, producing [MoO3(L)]2-. Similarly, the reaction of [Cu(LH2)]+ with [MoO4]2- formed the heterodinuclear complex [CuMoO3(L)]-. Both complexes were characterized by multinuclear NMR, UV-vis, and HRMS. HRMS in both cases confirmed the constitution of the complexes, containing molecular ions with the expected isotopic distribution.

One electron reduction transforms high-valent low-spin cobalt alkylidene into high-spin cobalt(ii) carbene radical.

One electron reduction of formally CoIV(OR)2(CPh2) forms the [CoII(OR)2(CPh2)]- anion. Whereas low-spin Co(OR)2([double bond, length as m-dash]CPh2) demonstrated significant alkylidene character, the high-spin [Co(OR)2(CPh2)]- anion features a rare Co(ii)-carbene radical. Treatment of [Co(OR)2(CPh2)][CoCp*2] with xylyl isocyanide triggers formation of two new C-C bonds, and is likely mediated by nucleophilic attack of deprotonated CoCp*2+ on a transient ketenimine.

Synthesis of Chromium(II) Complexes with Chelating Bis(alkoxide) Ligand and Their Reactions with Organoazides and Diazoalkanes.

Synthesis of new chromium(II) complexes with chelating bis(alkoxide) ligand [OO]Ph (H2[OO]Ph = [1,1':4',1''-terphenyl]-2,2''-diylbis(diphenylmethanol)) and their subsequent reactivity in the context of catalytic production of carbodiimides from azides and isocyanides are described. Two different Cr(II) complexes are obtained, as a function of the crystallization solvent: mononuclear Cr[OO]Ph(THF)2 (in toluene/THF, THF = tetrahydrofuran) and dinuclear Cr2([OO]Ph)2 (in CH2Cl2/THF). The electronic structure and bonding in Cr[OO]Ph(THF)2 were probed by density functional theory calculations. Isolated Cr2([OO]Ph)2 undergoes facile reaction with 4-MeC6H4N3, 4-MeOC6H4N3, or 3,5-Me2C6H3N3 to yield diamagnetic Cr(VI) bis(imido) complexes; a structure of Cr[OO]Ph(N(4-MeC6H4))2 was confirmed by X-ray crystallography. The reaction of Cr2([OO]Ph)2 with bulkier azides N3R (MesN3, AdN3) forms paramagnetic products, formulated as Cr[OO]Ph(NR). The attempted formation of a Cr-alkylidene complex (using N2CPh2) instead forms chromium(VI) bis(diphenylmethylenehydrazido) complex Cr[OO]Ph(NNCPh2)2. Catalytic formation of carbodiimides was investigated for the azide/isocyanide mixtures containing various aryl azides and isocyanides. The formation of carbodiimides was found to depend on the nature of organoazide: whereas bulky mesitylazide led to the formation of carbodiimides with all isocyanides, no carbodiimide formation was observed for 3,5-dimethylphenylazide or 4-methylphenylazide. Treatment of Cr2([OO]Ph)2 or H2[OO]Ph with NO+ leads to the formation of [1,2-b]-dihydroindenofluorene, likely obtained via carbocation-mediated cyclization of the ligand.

Characterization of Terminal Iron(III)-Oxo and Iron(III)-Hydroxo Complexes Derived from O2 Activation.

O2 activation at nonheme iron centers is a common motif in biological systems. While synthetic models have provided numerous insights into the reactivity of high-valent iron-oxo complexes related to biological processes, the majority of these complexes are synthesized using alternative oxidants. This report describes O2 activation by an iron(II)-triflate complex of the imino-functionalized tris(pyrrol-2-ylmethyl)amine ligand framework, H3[N(piCy)3]. Initial reaction conditions result in the formation of a mixture of oxidation products including terminal iron(III)-oxo and iron(III)-hydroxo complexes. The relevance of these species to the O2 activation process is demonstrated through reactivity studies and electrochemical analysis of the iron(III)-oxo complex.

Mechanistic and Kinetic Studies of the Ring Opening Metathesis Polymerization of Norbornenyl Monomers by a Grubbs Third Generation Catalyst.

The mechanism of ring-opening metathesis polymerization (ROMP) for a set of functionalized norbornenyl monomers initiated by a Grubbs third generation precatalyst [(H2IMes)(pyr)2(Cl)2Ru═CHPh] was investigated. Through a series of 12C/13C and 1H/2H kinetic isotope effect studies, the rate-determining step for the polymerization was determined to be the formation of the metallacyclobutane ring. This experimental result was further validated through DFT calculations showing that the highest energy transition state is metallacyclobutane formation. The effect of monomer stereochemistry (exo vs endo) of two types of ester substituted monomers was also investigated. Kinetic and spectroscopic evidence supporting the formation of a six-membered chelate through coordination of the proximal polymer ester to the Ru center is presented. This chelation and its impact on the rate of polymerization are shown to vary based on the monomer employed and its stereochemistry. The combination of this knowledge led to the derivation of a generic rate law describing the rate of polymerization of norbornene monomers initiated by a Grubbs third generation catalyst.

Ten-year legacy of organic carbon in non-agricultural (brownfield) soils restored using green waste compost exceeds 4 per mille per annum: Benefits and trade-offs of a circular economy approach.

Soil organic carbon (SOC) was re-analysed 10 years after application of source-segregated green waste compost at a 1 ha previously-developed UK site to compare with the increases suggested by the 4 per mille initiative proposed at COP21 in Paris. Compost prepared to PAS100 standard had been incorporated once at rates of 250, 500 and 750 t·ha-1 in 2007 in clay subsoil prior to planting of perennial energy crops. Our results show statistically significant differential increases in SOC, total nutrients N and P, or contaminants Zn, Pb, Cu, As and B, remain from the compost application after a decade. For the 500 or 750 t·ha-1 compost rates the SOC increments in the upper 10-15 cm were 0.85% or 1.6% over the 4.9% developed from a baseline of 1.8% in control areas by a decade of natural regeneration. Calculation of the elemental loadings from the compost analyses compared to the present-day levels suggests SOC declines after application at an average annual rate approaching 10%, compared to 5% for the nutrients or contaminants, roughly equivalent to half-lives of 5 or 10 years respectively. The study demonstrates the long-term soil organic matter (SOM) additions, fertility benefits and technical feasibility of a one-off, high-rate application of waste-derived compost to improve urban soils, compared to the potential trade-off of adding to PTE loadings. This longevity of SOC addition, previously unrecognised in brownfield soils, may be inferred for other areas where further cultivation is precluded, as is typical after landscape restoration or under perennial energy crops for the production of biomass. This unprecedented result has wider implications for marginal land use for bioenergy and the opportunities therein for SOC management using anthropogenic organic wastes to mitigate greenhouse gas emissions.

Tying the alkoxides together: an iron complex of a new chelating bulky bis(alkoxide) demonstrates selectivity for coupling of non-bulky aryl nitrenes.

New chelating bis(alkoxide) ligand H2[OO]Ph and its iron(ii) complex Fe[OO]Ph(THF)2 are described. The coordination of the ligand to the metal center is reminiscent of the coordination of two monodentate alkoxides in previously reported Fe(OR)2(THF)2 species. Fe[OO]Ph(THF)2 catalyzes selective and efficient dimerization of non-bulky aryl nitrenes to yield the corresponding azoarenes.

Transition metal-mediated reductive coupling of diazoesters.

The first transition metal mediated reductive coupling of diazoesters through the terminal nitrogens is reported. The resulting tetrazene-bridged bis(diazenylacetate) serves as a novel dinucleating ligand to iron(III). DFT calculations suggest that the reductive coupling takes place via a κ2 intermediate, which induces significant radical character on the terminal nitrogen.

Decreasing Risk of First and Subsequent Surgeries in Patients With Crohn's Disease in England From 1994 through 2013.

BACKGROUND & AIMS: Gastrointestinal (GI) surgery is an important part of the treatment algorithm for patients with Crohn's disease (CD) that is complicated or does not respond to medical therapy. Cohort studies from Denmark and Canada have shown that the risk of primary surgery is decreasing but there is a lack of contemporary data on subsequent resections. We examined trends in first and second GI resections in patients with CD. METHODS: We performed a retrospective cohort study using the United Kingdom primary care database ResearchOne, collecting data from patients with Crohn's disease from 1994 through 2013. We compared rates of first and second GI resections with etiological factors. RESULTS: Among 3059 incident cases of CD, 13%, 21%, and 26% of the patients underwent surgical resections after 1, 5, and 10 years, respectively. Of patients with an initial resection, 20% required an additional operation when followed for 10 years after the initial resection. We found a significant reduction in first surgery, from 44% to 21% after 10 years of disease, from 1994 to 2003 (χ2 for trend, P < .05). There was a significant reduction in second resections, in a 10-year follow-up period, from 40% in 1994 to 17% in 2003 (χ2 for trend, P < .05). Duration of disease, younger age at diagnosis, smoking, and immunomodulator use were positively associated with first surgeries. Duration of disease was significantly associated with the risk of undergoing a second resection. CONCLUSION: In a retrospective analysis of a United Kingdom primary care database, we observed a significant reduction in first and subsequent GI surgeries among patients with CD over the past 20 years in England.

Management of spontaneous and iatrogenic perforations, leaks and fistulae of the upper gastrointestinal tract.

Upper gastrointestinal perforations, leaks and fistulae are relatively common occurrences with a growing number of these complications occuring as a result of therapeutic advancement and adoption of newer and bolder endoscopic therapies. Historically, these were predominantly managed surgically; however, owing to high morbidity and mortality associated with surgical repair, endoscopic options are preferable. Over the past decade, vast expansion in the endoscopic armamentarium for the management of perforations, leaks and fistulae has led to endoscopic management now being the first-line treatment. Here, we will review the endoscopic modalities including through-the-scope clips, over-the-scope clips, stents, vacuum therapy, endoscopic sutures and sealants. In addition, we will discuss nonendoscopic approach to management including early recognition of perforations, ways to reduce septic complications and format algorithms to guide therapy for different scenarios. However, it is important to stress that there is a lack of high-quality randomised studies to clearly guide management of such complications, resulting in a wide variation of approaches in management by specialists. Each case requires some degree of individualisation due to the potential array of problems encountered and patient-specific co-morbidities. In the future, more robust studies are clearly required to better guide specialist management.