Brønsted Base-Induced Rearrangement and Nucleophilic Addition of O/N-Functionalized NHCs and Relative Group 4 Metal Complexes for Ethylene Polymerization Catalysis

The O/N-functionalized NHC precursors 1-[RNHC­(O)­CH₂]-3-[2-OH-3,5-^<i>t</i>Bu₂-(C₆H₂)­CH₂]-imidazolium bromide, [H₃(<b>1a</b>–<b>f</b>)]Br (<b>a</b>: R = 2,6-^<i>i</i>Pr₂-(C₆H₃); <b>b</b>: R = 2,4,6-Me₃-(C₆H₂); <b>c</b>: R = 2,6-Me₂-(C₆H₃); <b>d</b>: R = 4-Me-(C₆H₄); <b>e</b>: R = 4-Cl-(C₆H₄); <b>f</b>: R = ^<i>t</i>Bu), have been synthesized and characterized. Reactions between the aryloxy/amido-NHC precursors [H₃(<b>1a</b>–<b>e</b>)]Br and Ag₂O resulted in the NHC rearrangement to compounds [2-OH-3,5-(<i>^t</i>Bu)₂-(C₆H₂)­CH₂]­[R]­NC­(O)-CH₂-(C₃N₂H₃) (<b>4a</b>–<b>e</b>) in 68–89% yield. The preliminary study suggested that, after deprotonation, the <i>o</i>-quinone methide (o-QM) intermediate was in situ generated by the C–N cleavage and proton transfer of the resultant aryloxybenzyl NHCs, followed by the nucleophilic attack of <i>o</i>-QM to the nitrogen atom of the amido group. Treatment of salicylaldimine-functionalized NHC precursor 1-^<i>i</i>Pr-3-[2-HO-C₆H₂-3,5-^<i>t</i>Bu₂-C­(H)N-CH₂CH₂]-imidazolium bromide, [H₂(2)]­Br, with sodium hydride and group 4 metal sources MCl₄(THF)₂ (M = Ti, Zr) step by step afforded rare zwitterionic complexes [M­(<b>13</b>)­Cl₄] (M = Ti, <b>10</b>; Zr, <b>11</b>) in 50–53% yield. The formation of phenolate-amine <b>13</b> was attributed to the nucleophilic addition of the formed NHC to the imine carbon after deprotonation. The corresponding products <b>4a</b> and {[Ti­(<b>13</b>)­Cl₄]₂(μ-O)} (<b>12</b>) from the controlled hydrolysis of <b>10</b> have been confirmed by X-ray single-crystal analysis. Two novel NHC precursors, {H₂(<b>5</b>)}Br and [H₃(<b>7</b>)]­Br, together with silver complex [Ag₂(<b>5</b>)₂] (<b>6</b>) were conveniently derived. Several relative group 4 metal complexes, [MX₂(<i>k</i>²-<i>N</i>,<i>O</i>-OC₆H₂-3,5-^<i>t</i>Bu₂-C­(H)N–-CH₂CH₂-Im)₂]­[Br]₂ (M = Zr, X = Cl, <b>8</b>; M = Hf, X = OSiMe₃, <b>9</b>) and [Ti(7)­Cl₂] (<b>14</b>), have been prepared and tested for ethylene polymerization with MAO as cocatalyst. Complex <b>14</b> showed the highest catalytic activity of up to ca. 114 kg PE/(mol Ti·h·atm) to produce linear polymer

Mendelian randomization analysis reveals the impact of physical and occupational activities on the risk of gastroesophageal reflux disease and Barrett’s esophagus

Recent studies have indicated that participating in physical activity may provide a safeguard against gastroesophageal reflux disease (GERD). Nevertheless, the precise links between physical and occupational activity and the occurrence of GERD and Barrett’s esophagus (BE) are still uncertain. Conducting univariate and multivariate Mendelian randomization investigations to examine the causal relationship between exposures and outcomes. Genetic variation simulation was used in randomized experiments. Data on physical and occupational activity were obtained from the UK Biobank and GWAS catalog. In the meantime, data on GERD and BE were extracted from a high quality meta-analysis. The results of univariate Mendelian randomization analysis using multiple methods suggest a causal relationship between strenuous sports or other forms of exercise (as a protective factor) and GERD/BE. At the same time, three types of occupational related physical activities, including heavy manual or physical work, shift work and walking or standing work, are risk factors for GERD/BE and have a causal relationship with them. These results were reconfirmed through multivariate Mendelian randomization analysis, which excluding the influence of other potential confounding factors. The findings indicated that strenuous sports or other forms of exercise could lower the likelihood of GERD/BE, while excessive physical strain in the workplace, prolonged periods of standing or walking, and shift work could raise the risk of GERD/BE. Acknowledging this risk and implementing suitable measures can contribute to the prevention of GERD and BE, thus mitigating the associated health burden.</p

Nickel-Catalyzed Regioselective Cross-Dehydrogenative Coupling of Inactive C(sp³)–H Bonds with Indole Derivatives

A nickel-catalyzed regiosepecific C2- versus C3-oxidative cross-coupling reaction of indoles with 1,4-dioxane and other inactive C­(sp³)–H bonds is described. The divergent synthesis of C­(sp³)–C­(sp²) bonds was achieved in satisfactory yields with di-<i>tert</i>-butyl peroxide (DTBP) as the oxidant, which provides an efficient strategy for the selective construction of cyclic ethers containing heteroaromatic core structures

Cross-Coupling of Remote <i>meta</i>-C–H Bonds Directed by a U‑Shaped Template

<i>meta</i>-C–H arylation and methylation of 3-phenylpropanoic acid and phenolic derivatives were developed using an easily removable nitrile template. The combination of a weakly coordinating U-shaped template and mono-protected amino acid ligand was crucial for the cross-coupling of C–H bonds with organoborons

Observation by Real-Time NMR and Interpretation of Length- and Location-Dependent Deamination Activity of APOBEC3B

Human APOBEC3B (A3B) deaminates a cytosine into a uracil in single-stranded (ss) DNA, resulting in human cancers. A3B’s deamination activity is conferred by its C-terminal domain (CTD). However, little is known about the mechanism by which target sequences are searched and deaminated. Here, we applied a real-time NMR method to elucidate the deamination properties. We found that A3B CTD shows higher activity toward its target sequence in short ssDNA and efficiently deaminates a target sequence located near the center of ssDNA. These properties are quite different from those of well-studied APOBEC3G, which shows higher activity toward its target sequence in long ssDNA and one located close to the 5′-end. The unique properties of the A3B CTD can be rationally interpreted by considering that after nonspecific binding to ssDNA, A3B slides only for a relatively short distance and tends to dissociate from the ssDNA before reaching the target sequence

Regulatory T cells and the expression of related cytokines in different patient groups.

<p>1. Group 1 was compared with either Group 2 or Group 3, t  = 4.57, P<0.05 and t  = 4.89, P<0.05, respectively;</p><p>2. t  = 5.05, P<0.05 and t  = 7.72, P<0.05;</p><p>3. t  = 8.41, P<0.05 and t  = 11.08, P<0.05;</p><p>4. t  = 4.70, P<0.05 and t  = 9.18, P<0.05.</p

MIC (µg/mL) of the 15 antimicrobial agents^* to the 24 standard NTM strains.

<p>MIC, minimum inhibitory concentration; NTM, nontuberulous mycobacteria; RGM, rapidly growing mycobacteria; SGM, slowly growing mycobacteria; RIF, rifampicin; INH, isoniazid; STR, streptomycin; AK, amikacin; KM, kanamycin; CP, ciprofloxacin; OF, ofloxacin; LOF, levofloxacin; CAP, capreomycin; CEF, cefoxitin; DOX, doxycycline; MIN, minocycline; ETH, ethionamide; PAS, P-aminosalicylic acid; DIP, dipasic.</p><p>bold typeface indicates that the species was susceptible to the antimicrobial drug, while underlining indicates that the species was moderately susceptible to the antimicrobial drug.</p

Representative flow plots from a recovered TB patient labeled with anti-CD4, CD25 and Foxp3.

<p>Appropriate isotype controls were included to establish the positive gates. (I) FSC and SSC to identify lymphocytes. (II) CD4⁺ cells within the lymphocyte gate. (III) Cells were gated on the CD4⁺ cells shown in B and CD4⁺CD25⁺ cells were determined. (IV) Cells were gated on CD4⁺CD25⁺ cells and Foxp3 expression was determined.</p

Differences in regulatory T cells and expression of related cytokines in sputum smear negative and positive patients.

<p>1. Sputum smear positive patients were compared with smear negative patients, t  = 2.51, P<0.05;</p><p>2. t  = 3.19, P<0.05;</p><p>3. t  = 3.07, P<0.05;</p><p>4. t  = 5.16, P<0.05.</p

The susceptibility distributions to 15 antimicrobial agents of 12 standard slowly growing mycobacteria strains.

<p>The susceptibility distributions to 15 antimicrobial agents of 12 standard slowly growing mycobacteria strains.</p