Ruthenium-Catalyzed Dehydrogenative and Dehydrative C-H Coupling Reactions of Arenes with Alcohols and Carbonyl Compounds

Despite their outstanding achievements, the requirement of preformed functional groups and wasteful byproduct formation are inherent disadvantages associated with the transition metal catalyzed cross-coupling methods. Inspired by the needs for green and sustainable chemistry, transition metal catalyzed dehydrogenative and dehydrative coupling methods have been recognized as environmentally sustainable and atom economical synthetic routes for the new C-C bond formation. The catalytic activation of C-H and C-O bonds allows the formation of coupling products from ubiquitous hydrocarbon substrates by releasing hydrogen or water byproduct. However, these novel protocols require relatively harsh conditions due to their low reactivity of C-H and C-O bonds, and difficulty in controlling regioselectivity. The development of new catalytic C-H bond activation methods is highly desirable for the selective C-C formation reactions. The cationic ruthenium-hydride complex was found to be a highly effective catalyst for the dehydrogenative and dehydrative C-H coupling reactions of simple arenes with alcohols and carbonyl compounds. The dehydrogenative coupling reaction of phenols with aldehydes formed the 2-acylphenols without using any metal oxidant or forming wasteful byproducts. The mechanistic studies suggested that the aldehyde substrate was served as both the coupling partner and hydrogen acceptor. The coupling method was successfully extended to the synthesis of 2H-chromene derivatives by using α,β-unsaturated aldehydes. The cationic ruthenium-hydride complex was found to exhibit uniquely high activity for the coupling reaction of phenols with ketones to form synthetically useful 2-vinylphenols. The coupling of phenols with linear ketones led to a highly (Z)-selective formation of trisubstituted olefins. We also developed the catalytic synthesis of biologically important indole and quinoline derivatives from the coupling reaction of arylamines with diols. A broad range of substrates was demonstrated to afford the regioselective N-heteroannulated products. The deuterium labeling study and control experiments were performed to discern the mechanistic pathway

Suffering from Vaccines or from Government? : Partisan Bias in COVID-19 Vaccine Adverse Events Coverage

Vaccine adverse events have been presumed to be a relatively objective measure that is immune to political polarization. The real-world data, however, shows the correlation between presidential disapproval ratings and the subjective severity of adverse events. This paper investigates the partisan bias in COVID vaccine adverse events coverage with language models that can classify the topic of vaccine-related articles and the political disposition of news comments. Based on 90K news articles from 52 major newspaper companies, we found that conservative media are inclined to report adverse events more frequently than their liberal counterparts, while the coverage itself was statistically uncorrelated with the severity of real-world adverse events. The users who support the conservative opposing party were more likely to write the popular comments from 2.3K random sampled articles on news platforms. This research implies that bipartisanship can still play a significant role in forming public opinion on the COVID vaccine even after the majority of the population's vaccinationComment: 5 pages, 5 figures, 2 table

Synthesis of Symmetric and Unsymmetric Secondary Amines from the Ligand-Promoted Ruthenium-Catalyzed Deaminative Coupling Reaction of Primary Amines

The catalytic system generated in situ from the tetranuclear Ru–H complex with a catechol ligand (1/L1) was found to be effective for the direct deaminative coupling of two primary amines to form secondary amines. The catalyst 1/L1 was highly chemoselective for promoting the coupling of two different primary amines to afford unsymmetric secondary amines. The analogous coupling of aniline with primary amines formed aryl-substituted secondary amines. The treatment of aniline-d7 with 4-methoxybenzylamine led to the coupling product with significant deuterium incorporation on CH2 (18% D). The most pronounced carbon isotope effect was observed on the α-carbon of the product isolated from the coupling reaction of 4-methoxybenzylamine (C(1) = 1.015(2)). A Hammett plot was constructed from measuring the rates of the coupling reaction of 4-methoxyaniline with a series of para-substituted benzylamines 4-X-C6H4CH2NH2 (X = OMe, Me, H, F, CF3) (ρ = −0.79 ± 0.1). A plausible mechanistic scheme has been proposed for the coupling reaction on the basis of these results. The catalytic coupling method provides an operationally simple and chemoselective synthesis of secondary amine products without using any reactive reagents or forming wasteful byproducts

A theory-based practical solution to correct for sex-differential participation bias

Most genomic cohorts are retrospective where the exposures and outcomes are predetermined prior to sample collection. Therefore, a spurious association between an exposure and an outcome can arise if both variables affect study participation. Such concerns were raised in previous studies questioning the representativeness of the UK Biobank. Recently, a genome-wide association study (GWAS) on biological sex found many autosomal hits and non-negligible autosomal heritability which the authors attribute to selection bias. In this study, we propose a simple and a practical method that can overcome sex-driven selection bias based on theoretical analysis and simulations.This work was supported by the National Research Foundation of Korea (NRF) (Grant number 2022R1A2B5B02001897) funded by the Korean government, Ministry of Science, and ICT. This study was supported by the Creative-Pioneering Researchers Program funded by Seoul National University (SNU)

Outcomes of Descemet's membrane endothelial keratoplasty performed in combination with, before, or after cataract surgery in Fuchs' endothelial dystrophy: A review of the literature and meta-analysis

This review aimed to compare the outcomes of Descemet's membrane endothelial keratoplasty (DMEK) in combination with (category 1), before (category 2), or after cataract surgery (category 3) in patients with Fuchs' endothelial dystrophy (FED). Primary outcome was gain in best-corrected log of minimum angle of resolution (logMAR) visual acuity (BCVA). Secondary outcomes were graft detachment, rebubbling rates, rejection, failure, and endothelial cell loss (ECL). In category 1, 2, and 3, 12 studies (N = 1932) were included (five in category 1 [n = 696], one in category 2 [n = 286], and two in category 3 [n = 950], and the remaining four compared between two of the three categories). At 6 months, the gain in BCVA was 0.34 ± 0.04, 0.25 ± 0.03, and 0.38 ± 0.03 logMAR in category 1, 2, and 3, respectively. The difference was significant between categories 1 and 2 (Chi2 = 11.47, P < 0.01) and categories 2 and 3 (Chi2 = 35.53, P < 0.01). At 12 months, the gain in BCVA was 0.52 ± 0.05 and 0.38 ± 0.06 logMAR in categories 1 & 3 (Chi2 = 14.04, P < 0.01). The rebubbling rates were 15%, 4%, and 10% (P < 0.01) and the graft detachment rates were 31%, 8%, and 13% (P < 0.01) in categories 1, 2, and 3, respectively. However, graft rejection, survival rates, and ECL at 12 months were not different between categories 1 and 3. There is low certainty evidence that gain in BCVA in category 1 was comparable to category 3 at 6 months; however, it was significantly better with category 3 at 12 months. Although rebubbling and graft detachment rates were highest in category 1, there was no significant difference in graft rejection, survival rates, and ECL. Further high-quality studies are likely to change the effect estimate and have an impact on the confidence of the estimate

Annulation of O-silyl N,O-ketene acetals with alkynes for the synthesis of dihydropyridinones and its application in concise total synthesis of phenanthroindolizidine alkaloids

The formation of N-heterocycles with multiple substituents is important in organic synthesis. Herein, we report a novel method for the construction of functionalized dihydropyridinone rings through the annulation of an amide α-carbon with a tethered alkyne moiety. The reaction of the amide with the alkyne was achieved via O-silyl N,O-ketene acetal formation and silver-mediated addition. Furthermore, the developed method was applied for the total synthesis of phenanthroindolizidine and phenanthroquinolizidine alkaloids. By varying the coupling partners, a concise and collective total synthesis of these alkaloids was achieved

Quaternary structures of Vac8 differentially regulate the Cvt and PMN pathways.

Armadillo (ARM) repeat proteins constitute a large protein family with diverse and fundamental functions in all organisms, and armadillo repeat domains share high structural similarity. However, exactly how these structurally similar proteins can mediate diverse functions remains a long-standing question. Vac8 (vacuole related 8) is a multifunctional protein that plays pivotal roles in various autophagic pathways, including piecemeal microautophagy of the nucleus (PMN) and cytoplasm-to-vacuole targeting (Cvt) pathways in the budding yeast Saccharomyces cerevisiae. Vac8 comprises an H1 helix at the N terminus, followed by 12 armadillo repeats. Herein, we report the crystal structure of Vac8 bound to Atg13, a key component of autophagic machinery. The 70-angstrom extended loop of Atg13 binds to the ARM domain of Vac8 in an antiparallel manner. Structural, biochemical, and in vivo experiments demonstrated that the H1 helix of Vac8 intramolecularly associates with the first ARM and regulates its self-association, which is crucial for Cvt and PMN pathways. The structure of H1 helix-deleted Vac8 complexed with Atg13 reveals that Vac8[Delta 19-33]-Atg13 forms a heterotetramer and adopts an extended superhelical structure exclusively employed in the Cvt pathway. Most importantly, comparison of Vac8-Nvj1 and Vac8-Atg13 provides a molecular understanding of how a single ARM domain protein adopts different quaternary structures depending on its associated proteins to differentially regulate 2 closely related but distinct cellular pathways