Carbon supported hybrid catalysts for controlled product selectivity in the hydrosilylation of alkynes

A series of Rh- and Ir-hybrid catalysts with varying tether lengths has been prepared by immobilization of RhI, RhIIIand IrIIIcomplexes on carbon blackviaradical grafting. The performance of the different catalysts was assessed for the hydrosilylation of phenylacetylene with Et3SiH. The efficiency of the catalysts was dependent on the length of the tethers to the surface. The RhIII- and IrIIIhybrids afforded the β(Z)-vinylsilanes, as observed for the analogous homogeneous RhIIIcatalyst. No distinct product selectivity was observed when using the homogeneous RhIprecursors as catalysts. However, on using the RhIIIhybrid catalysts derived from the RhIprecursors to promote hydrosilylation, the major products were the α-vinylsilanes and the origin of the difference in reactivity was found to be a chemical modification of the catalysts during immobilization. Substrate scope is demonstrated for a number of alkynes, and feasible mechanisms supported by DFT calculations are proposed

Djelovanje karboksilnih kiselina na crveno obojenje cvjetova žutinice

Eight carboxylic acids were fed at 1-10000 pM to the flower pastes from fresh dyer’s saffron (Carthamus tinctorius L.) capitula and their effects on the red colouration investigated. Glyoxyllic acid, glycolic acid, oxaloacetic acid, 2-oxoglutaric acid and gluconic acid were found to be positive stimulators for the reaction, while succinic acid, malic acid and citric acid inhibited the colour change.Svojim ranijim istraživanjima autori su pokazali da usitnjeni cvjetovi žutinice (Carthamus tinctorius L.) poprime crvenu boju ako na njih djeluju otopine aminokiselina. Učinkovitost pojedine aminokiseline ovisi o tipu: kisele amino- kiseline bile su najučinkovitije, neutralne nešto manje, one s aromatičnim skupinama ili skupinama sa sumporom još manje, dok su bazične aminokiseline bile najmanje učinkovite. Za objašnjenje ovih rezultata bilo je potrebno da se ustanove još drugi metaboliti koji biokatalitički utječu na promjenu boje cvjetova. U ovom prilogu autori objavljuju podatke o promjenama boje nakon primjene karboksilnih kiselina. U tu svrhu istražili su djelovanje osam karboksilnih kiselina u koncentracijama od 1 - 10000 pM na kašu od zdrobljenih cvjetova žutinice (Carthamus tinctorius L.). Postignuti rezultati su pokazali da glioksilna, glikolna, oksalooc- tena, 2-oksoglutarna i glukonska kiselina pospješuju reakciju stvaranja crvenog bojila, dok jantarna, jabučna i limunska kiselina tu reakciju inhibiraju. U radu se navode točni podaci o materijalu, metodama rada i rezultatima koji su prikazani u preglednoj tabeli. Rezultate autori kratko komentiraju uz razmišljanja da bi kemijske strukture karboksilnih kiselina mogle biti uže povezane s procesima promjene bojila, iako je sam mehanizam reakcije zasad još nepoznat

Rh-POP Pincer Xantphos Complexes for C-S and C-H Activation. Implications for Carbothiolation Catalysis

The neutral Rh­(I)–Xantphos complex [Rh­(κ³-_P,O,P-Xantphos)­Cl]_<i>n</i>, <b>4</b>, and cationic Rh­(III) [Rh­(κ³-_P,O,P-Xantphos)­(H)₂]­[BAr^F₄], <b>2a</b>, and [Rh­(κ³-_P,O,P-Xantphos-3,5-C₆H₃(CF₃)₂)­(H)₂]­[BAr^F₄], <b>2b</b>, are described [Ar^F = 3,5-(CF₃)₂C₆H₃; Xantphos = 4,5-bis­(diphenylphosphino)-9,9-dimethylxanthene; Xantphos-3,5-C₆H₃(CF₃)₂ = 9,9-dimethylxanthene-4,5-bis­(bis­(3,5-bis­(trifluoromethyl)­phenyl)­phosphine]. A solid-state structure of <b>2b</b> isolated from C₆H₅Cl solution shows a κ¹-chlorobenzene adduct, [Rh­(κ³-_P,O,P-Xantphos-3,5-C₆H₃(CF₃)₂)­(H)₂(κ¹-ClC₆H₅)]­[BAr^F₄], <b>3</b>. Addition of H₂ to <b>4</b> affords, crystallographically characterized, [Rh­(κ³-_P,O,P-Xantphos)­(H)₂Cl], <b>5</b>. Addition of diphenyl acetylene to <b>2a</b> results in the formation of the C–H activated metallacyclopentadiene [Rh­(κ³-_P,O,P-Xantphos)­(ClCH₂Cl)­(σ,σ-(C₆H₄)­C­(H)CPh)]­[BAr^F₄], <b>7</b>, a rare example of a crystallographically characterized Rh–dichloromethane complex, alongside the Rh­(I) complex <i>mer</i>-[Rh­(κ³-_P,O,P-Xantphos)­(η²-PhCCPh)]­[BAr^F₄], <b>6</b>. Halide abstraction from [Rh­(κ³-_P,O,P-Xantphos)­Cl]_<i>n</i> in the presence of diphenylacetylene affords <b>6</b> as the only product, which in the solid state shows that the alkyne binds perpendicular to the κ³-POP Xantphos ligand plane. This complex acts as a latent source of the [Rh­(κ³-_P,O,P-Xantphos)]⁺ fragment and facilitates <i>ortho</i>-directed C–S activation in a number of 2-arylsulfides to give <i>mer</i>-[Rh­(κ³-_P,O,P-Xantphos)­(σ,κ¹-Ar)­(SMe)]­[BAr^F₄] (Ar = C₆H₄COMe, <b>8</b>; C₆H₄(CO)­OMe, <b>9</b>; C₆H₄NO₂, <b>10</b>; C₆H₄CNCH₂CH₂O, <b>11</b>; C₆H₄C₅H₄N, <b>12</b>). Similar C–S bond cleavage is observed with allyl sulfide, to give <i>fac</i>-[Rh­(κ³-_P,O,P-Xantphos)­(η³-C₃H₅)­(SPh)]­[BAr^F₄], <b>13</b>. These products of C–S activation have been crystallographically characterized. For <b>8</b> in situ monitoring of the reaction by NMR spectroscopy reveals the initial formation of <i>fac</i>-κ³-<b>8</b>, which then proceeds to isomerize to the <i>mer</i>-isomer. With the <i>para</i>-ketone aryl sulfide, 4-SMeC ₆H₄COMe, C–H activation <i>ortho</i> to the ketone occurs to give <i>mer</i>-[Rh­(κ³-_P,O,P-Xantphos)­(σ,κ¹-4-(COMe)­C₆H₃SMe)­(H)]­[BAr^F₄], <b>14</b>. The temporal evolution of carbothiolation catalysis using <i>mer</i>-κ³-<b>8</b>, and phenyl acetylene and 2-(methylthio)­acetophenone substrates shows initial fast catalysis and then a considerably slower evolution of the product. We suggest that the initially formed <i>fac</i>-isomer of the C–S activation product is considerably more active than the <i>mer</i>-isomer (i.e., <i>mer</i>-<b>8</b>), the latter of which is formed rapidly by isomerization, and this accounts for the observed difference in rates. A likely mechanism is proposed based upon these data

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Carbon-carbon bond construction using boronic acids and aryl methyl sulfides: orthogonal reactivity in Suzuki-type couplings

The Rh(i)-catalysed coupling of aryl and alkenyl boronic acids with simple aryl and alkenyl methyl sulfides is reported. The process employs bench-stable Rh(i) precatalysts incorporating small bite-angle chelating phosphine ligands (R2PCH2PR2, R = iPr, Cy), shows good functional group tolerance, and proceeds under mild reaction conditions. Importantly, aryl bromide activating groups are inert to the reaction conditions, allowing selective reaction at either a methyl sulfide or bromide activating group, depending on catalyst (metal) choice. The scope of the coupling reactions, their combination with Rh-catalysed hydroacylation reactions in cascade processes, together with preliminary mechanistic studies, are all documented. This journal is © The Royal Society of Chemistry 2013

Bis(phosphine)boronium salts. Synthesis, structures and coordination chemistry.

The synthesis of a range of bis(phosphine)boronium salts is reported [(R2HP)2BH2][X] (R = Ph, (t)Bu, Cy) in which the counter anion is also varied (X(-) = Br(-), [OTf](-), [BAr(F)4](-), Ar(F) = 3,5-(CF3)2C6H3). Characterization in the solid-state by X-ray diffraction suggests there are weak hydrogen bonds between the PH units of the boronium cation and the anion (X(-) = Br(-), [OTf](-)), while solution NMR spectroscopy also reveals hydrogen bonding occurs in the order [BAr(F)4](-) &lt; [OTf](-) &lt; Br(-). [(Ph2HP)2BH2][BAr(F)4] reacts with RhH(PPh3)3, by elimination of H2, forming [Rh(κ(1),η-PPh2BH2·PPh2H)(PPh3)2][BAr(F)4] which shows a β-B-agostic interaction from the resulting base stabilised phosphino-borane ligand. Alternatively such ligands can be assembled directly on the metal centre by reaction of in situ generated {Rh(PPh3)3}(+) and Ph2HP·BH3 to afford [Rh(κ(1),η-PPh2BH2·PPh3)(PPh3)2][BAr(F)4], which was characterised by X-ray crystallography. Addition of H3B·PPh2H to the well-defined 16-electron "T-shaped" complex [Rh(P(i)Bu3)2(PPh3)][BAr(F)4] (characterised by X-ray crystallography) formed of a mixture of base-stabilised phosphino borane ligated complexes [Rh(κ(1),η-PR2BH2·PR3)(PR3)2][BAr(F)4] (R = (i)Bu or Ph). These last observations may lend clues to the formation of bis(phosphine)boronium salts in the catalytic dehydrocoupling reaction of phosphine boranes as mediated by Rh(I) compounds

Relative binding affinities of fluorobenzene ligands in cationic rhodium bisphosphine η 6-fluorobenzene complexes probed using collision-induced dissociation

A range of cationic rhodium bisphosphine η 6-fluorobenzene (fluorobenzenes = C6H6-n F n , n = 1-3) and related complexes have been synthesized and characterized. These complexes act as useful organometallic precursors for catalysis or further synthetic elaboration. The relative binding affinity of the arene ligands has been investigated using Electrospray Ionisation Mass Spectrometry (ESI-MS) and two different collision-induced dissociation (CID) techniques. The influence of arene fluorination upon arene binding affinity is discussed as well as the comparison of different bis-phosphine ligands with regard to bite angle and phosphine substitution. We show that this simple technique allows fast and easy comparison of the binding affinity of arene ligands to cationic organometallic fragments

Immunotherapy for Chordoma and Chondrosarcoma: Current Evidence

Chordomas and chondrosarcomas are rare but devastating neoplasms that are characterized by chemoradiation resistance. For both tumors, surgical resection is the cornerstone of management. Immunotherapy agents are increasingly improving outcomes in multiple cancer subtypes and are being explored in chordoma and chondrosarcoma alike. In chordoma, brachyury has been identified as a prominent biomarker and potential molecular immunotherapy target as well as PD-1 inhibition. While studies on immunotherapy in chondrosarcoma are sparse, there is emerging evidence and ongoing clinical trials for PD-1 as well as IDH inhibitors. This review highlights potential biomarkers and targets for immunotherapy in chordoma and chondrosarcoma, as well as current clinical evidence and ongoing trials