Expression, purification, crystallization and preliminary crystallographic analysis of a putative Clostridium difficile surface protein Cwp19

Cwp19 is a putatively surface-located protein from Clostridium difficile. A recombinant N-terminal protein (residues 27–401) lacking the signal peptide and the C-terminal cell-wall-binding repeats (PFam04122) was crystallized using the sitting-drop vapour-diffusion method and diffracted to 2 Å resolution

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all >0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Stereoselective epoxide generation with cyclic rhodium carbenoids: A new access to spiro-indolooxiranes

The reaction of cyclic diazoamides with aryl aldehydes catalyzed by rhodium(II) acetate leads to intermolecular stereoselective epoxide ring formation. A series of spiro-indolooxiranes has been synthesized following the described method in a facile manner. The use of aryl dialdehydes in the course of reaction of cyclic diazoamide resulted the formation of bis-spiro-indolooxiranes

Synthesis of the first polymeric Cu(I) dppe (dppe = 1,2-bis(diphenylphosphino)ethane) complexes

The first polymeric Cu(I) dppe complexes have been synthesized and their structures in solution and solid state have been studied

Synthesis and structural characterization of a new ruthenium hydride ethylene complex

167-170A ruthenium(II) ethylene complex, trans-[Ru(H)(C2H4)-(dppm)2][BF4], bearing two 1,1-bis(diphenylphosphino) methane (dppm) ligands has been synthesized and structurally characterized using X-ray crystallography. In the molecular structure, the RuII center shows a distorted octahedral coordination geometry formed by four P atoms of the two chelating dppm ligands, a hydride, and an ethylene ligands. The four dppm P atoms are almost co-planar with the hydride and the ethylene ligands perpendicular to this plane. The C-C bond distance of the bound ethylene is 1.375(6) Å, which is elongated by 0.042 Å as compared to free ethylene (1.333(2) Å). The packing diagram of the complex shows two voids or channels, which are occupied by BF4– counterion and water molecules

Novel double dealkylation of trialkylphosphite in the presence of an acid: synthesis and characterization of a 16-electron ruthenium complex bearing P(OH)₂(OMe) ligand

A stable, coordinatively unsaturated, 16-electron ruthenium complex bearing P(OH)2(OMe) has been synthesized and characterized. It reacts with H2 resulting in a highly acidic dihydrogen complex

Reactions of Cu3(dppm)3(μ3−OH)(ClO4)2Cu_3(dppm)_3(\mu_3-OH)(ClO_4)_2 (dppm=bis-(diphenylphosphino) methane) with Soft Heterocumulenes

The reaction of $[Cu_3(dppm)_3(\mu_3-OH)](ClO_4)_2$ (1) with heterocumulenes (X‚C‚S; X=NPh, NMe and S) has been studied. The $\mu_3-OH$ ligand inserts into PhNCS and MeNCS only in the presence of methanol. Insertion products are formed in accord with earlier observations made with copper(I)–aryloxides. On heating, the insertion products convert to a S bridged cluster $[Cu_4(dppm)_4(\mu_4- S)](ClO_4)_2$ (8), having a tetrameric core. However, in the reaction with $CS_2$, 1 is converted to 8 even at room temperature in the presence of methanol. On the other hand, the dimeric complex $[Cu_2(dppm)_2(CH_3CN)_4](ClO_4)_2$, reacts with $CS_2$ to give (diphenylphosphinomethyl)- diphenylphosphine sulfide, $Ph_2P–CH_2–P(=S)Ph_2$ (dppmS), which forms the complex $[Cu(dppmS)_2]ClO_4$ (9). A single crystal X-ray crystallographic study of 9, the .rst copper(I) complex of dppmS has been taken up to con.rm the mono-oxidation of the dppm ligand and the nuclearity of the complex. Reactions of complex 1 with heterocumulenes and with elemental sulfur, are compared