Trimerisation of the cationic fragments [(η -ring)M(Aa)]+ ((η -ring) M=(η 5-C5Me5)Rh, (η 5-C5Me5)Ir, (η 6-p -MeC6H4i Pr)Ru; Aa=α -amino acidate) with chiral self-recognition: Synthesis, characterisation, solution studies and catalytic reactions of the trimers [{(η -ring)M(Aa)}3](BF4)3

The formation of [{(η-ring)M(Aa)}3](BF4)3 trimers [(η-ring)M=(η5-C5Me5)Rh, (η5-C5Me5)Ir, (η6-p-MeC6H4iPr)Ru; Aa = α-amino acidate, one cation shown schematically] takes place by chiral self-recognition, the RMRMRM or SMSMSM trimers are equally configurated at the metal centres and are the only diastereomers detected. The equilibrium constant for the diastereomerisation process between both isomers depends on the solvent, amino acidate, and metal. The trimers catalyse the reduction of unsaturated aldehydes to unsaturated alcohols and the reduction of acetophenone to 2-phenylethanol with up to 75 % ee.We thank the Direccion General de Investigacion Cientifica y Tecnica for financial support (GrantPB96/0845). F.J. is grateful to IBERDROLA S.A. for sponsoring A.K. acknowledges the travel grant of the European Community in the frame work of the project Catalysis by Metal Complexes involving Small Molecules(ERBCHRXCT930147).Peer reviewe

Tris(diphenylthiophosphinoyl)methanide as tripod ligand in rhodium(III), iridium(III) and ruthenium(II) complexes. Crystal structures of [(η5-C5Me5)Ir{η3-(SPPh2)3C-S,S′,S″}]BF4 and [(η6-MeC6H4Pri)Ru{η3-(SPPh2)3C-S,S′,S″}]BPh4

Reaction of the complex [{(η5-C5Me5)RhCl2}2], in CH2Cl2 solution, with AgBF4 (1:2 molar ratio) and (SPPh2)3CH leads to the cationic compound [(η5-C5Me5)RhCl{η2-(SPPh2)2CH(SPPh2)-S,S′}]BF4 (1) which is deprotonated by thallium(I) pyrazolate affording [(η5-C5Me5)Rh{η3-(SPPh2)3C−S,S′,S″}]BF4 (2a). The iridium dimer [(η5-C5Me5)IrCl2}2] reacts with silver salts and (SPPh2)3CH, in CH2Cl2 or Me2CO, under analogous conditions, affording mixtures of [(η5-C5Me5)IrCl{η2-(SPPh2)2)-S,S′}]+ and [(η5-C5Me5)Ir{η3-(SPPh2)3C-S,S′,S″}]A [A=BF4− (3a), PF6− (3b). Addition of Et3N to the mixture gives pure complexes 3. The ruthenium complexes [{η6j6-arene)RuCl2}2] (arene = C6Me6, p-MeC6H4Pri) react with (SPPh2)3CH, in the presence of AgA (A = PF6− or BF4−) or Na BPh4, in CH2Cl2 or Me2CO, yielding only the deprotonated complexes [(η6-arene)Ru{η3-(SPPH2)3C−S,S′,S″}]A [arene = C6Me6, A = BF4; arene = p-MeC6H4Pri, A - BPh4 (4a), PF6 (4b)]. The crystal structures of 3a and 4a were established by X-ray crystallography. Compound 3a crystallizes in the orthorhombic space group Pna21, with lattice parameters a-41.477(6), b = 10.6778(11), c = 20.162(3) Å and Z=8. Complex 4a crystallizes in a monoclinic lattice, space group P21/n, with a = 20.810(4), b = 12.555(3), c = 23.008(4) Å, β = 95.82(2)° and Z = 4. Both cationic complexes exhibit analogous pseudo-octahedml molecular structures with the anionic (SPPh2)3C− ligand bonded via the three sulphur atoms in a tripodal, tridentate fashion. Each metal centre completes its coordination environment with a η5-C5Me5 (3a) or a η6-MeC6H4Pri group (4a). A quite interesting result concerns the non-planarity of the methanide carbon which display P−C−P angles in the range 112.6–114.4(5)° in 3a and 111.9–113.6(4)° in 4a. The redox chemistry of the complexes was investigated by cyclic voltammetry. The Rh(III) complexes are quasi-reversibly reduced to Rh(I) and the Ir(III) complex is irreversibly reduced to IKD in acetonitrile solutions. The Ru(II) complex undergoes a quasi-reversible reduction to Ru(I) and a reversible oxidation to Ru(III).We thank the 'Fondo de Desarrollo Cientifico y Tecnologico, Chile' (Grant No. 460/93-95), Direccion de Investigacion y Postgrado, Pontificia Universidad Catolica de Chile (DlPUC), Fundacion Andes, Chile, and the Instituto de Cooperacion Iberoamericano, Spain, for financial support.Peer reviewe

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3

ObjectivesCARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain.MethodsIn total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC &gt; 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis.ResultsIn total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were blaOXA–48 (263/377), blaKPC–3 (62/377), blaVIM–1 (28/377), and blaNDM–1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5).ConclusionThis study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3

Enantioselective Friedel-Crafts alkylations catalysed by well-defined iridium and rhodium half-sandwich complexes

Aqua-complexes (SM,RC)-[CpM{(R)-prophos}(H 2O)][SbF6]2 (M = Rh 1, Ir 2) catalysed the alkylation of α,β-unsaturated aldehydes with aromatics and heteroaromatics but in some cases, mixtures of products were obtained. Complexes 1 and 2 were also used to activate nitroalkenes for the Friedel-Crafts alkylation of a variety of aromatics and heteroaromatics, in particular, 1,3,5-trimethoxybenzene. For this substrate, the monoalkylated adduct was obtained in quantitative yield with enantioselectivities of up to 73% ee being achieved. The intermediate catalyst/nitroalkene was isolated and characterized and the complex catalyst/adduct was detected spectroscopically. From these data a plausible catalytic cycle is proposed. © 2011 Elsevier Ltd. All rights reserved.We thank the Ministerio de Educación y Ciencia (Grant CTQ 2009-10303/BQU) and Gobierno de Aragón (Grupo Consolidado: Catalizadores Organometálicos Enantioselectivos) for financial support.Peer Reviewe

Chiral phosphinooxazoline-ruthenium(II) and - osmium(II) complexes as catalysts in Diels-Alder reactions

15 pages, 9 figures, 4 tables, scheme 3.The synthesis and characterization of optically active phosphinooxazoline chloride complexes (SM and RM)-[(η6-p-MeC6H4iPr)MCl(PN)]A (M = Ru, Os; PN = phosphinooxazoline ligand; A = counteranion) and the derived aqua complexes (RM and SM)-[(η6-p-MeC6H4iPr)M(PN)(H2O)](A)2 are reported. The OPOF2-containing compounds (RM and SM)-[(η6-p-MeC6H4iPr)M(OPOF2)(PNiPr)][PF6] (M = Ru, Os; PNiPr = (4S)-2-(2-diphenylphosphinophenyl)-4-isopropyl-1,3-oxazoline) have been also prepared and characterized. The molecular structures of (SM)-[(η6-p-MeC6H4iPr)MCl(PNiPr)][SbF6] (M = Ru, Os), (SRu)-[(η6-p-MeC6H4iPr)RuCl(PNInd)][SbF6] (PNInd = (3aS,8aR)-2-(2-diphenylphosphinophenyl)-3a,8a-dihydroindane [1,2-d]oxazole), and (RRu)-[(η6-p-MeC6H4iPr)Ru(PNiPr)(H2O)][SbF6] and that of the OPOF2-containing compounds (RRu and SRu)-[(η6-p-MeC6H4iPr)Ru(OPOF2)(PNiPr)][PF6] have been determined by X-ray diffractometric methods. Dichloromethane solutions of the aqua complexes [(η6-p-MeC6H4iPr)M(PN)(H2O)][SbF6]2 are active catalysts for the Diels−Alder reaction between methacrolein and cyclopentadiene. The reaction occurs rapidly at room temperature with good exo:endo selectivity (from 85:15 to 96:4) and moderate enantioselectivity (up to 47%). The intermediate Lewis acid−dienophile compound (RRu and SRu)-[(η6-p-MeC6H4iPr)Ru(PNInd)(methacrolein)][SbF6]2 was isolated, and the molecular structure of the S epimer was determined by diffractometric means. The osmium complexes (SOs and ROs)- [(η6-p-MeC6H4iPr)Os(PN)(H2O)][A]2 (PN = PNiPr, A = SbF6, BF4; PN = PNInd, A = SbF6) evolve to the phenyl-containing compounds (SOs and ROs)-[(η6-p-MeC6H4iPr)OsPh(PN‘)][SbF6] (PN‘ = (4S)-2-(2-hydroxyphenylphosphinophenyl)-4-isopropyl-1,3-oxazoline (PNOHiPr), PN‘ = (3aS,8aR)-2-(2-hydroxyphenylphosphinophenyl)-3a,8a-dihydroindane[1,2d]oxazole] (PNOHInd)) and (SOs and ROs)-[(η6-p-MeC6H4iPr)OsPh(PNFiPr)][BF4] (PNFiPr = (4S)-2-(2-fluorophenylphosphinophenyl)-4-isopropyl-1,3-oxazoline), respectively, in which the phosphinooxazoline ligand incorporates a hydroxy or fluoro functionality. On the basis of spectroscopic and crystallographic observations, a common pathway for these reactions is proposed.This work is dedicated to Dr. José Antonio Abad on the occasion of his retirement. We thank the Dirección General de Investigacion Científica y Técnica for financial support (Grants BQU 2000/0907, BQU2002-1729, and BQU 2003/1096). Authors thank CCLRC Daresbury Laboratory for allocation of synchrotron beam time (AP41).Peer reviewe

Rhodium(I) complexes with pyridine-2-aldehyde and related Schiff-base ligands

The synthesis of [Rh(TFB)(PyCH=NR)]ClO4 by reaction of the coordinated pyridine-2-aldehyde (PyCHO) moiety of [Rh(TFB)(PyCHO)]ClO4 with primary amines is described. They are active catalysts for the transfer of hydrogen from isopropanol to acetophenone. The catalytic activity depends upon the basicity of the parent amine. Reactions with carbon monoxide and triphenylphosphine give complexes [Rh(CO)2(PyCH=NR)]ClO4, [Rh(CO)(PPh3)2(PyCH=NR)]ClO4 and [Rh(CO)(PPh3)(PyCH=NR)]ClO4.Peer reviewe

Asymmetric 1,3-dipolar cycloaddition reactions between methacrylonitrile and nitrones catalysed by well-defined M(diphosphane) (M = Rh, Ir) complexes

The cationic half-sandwich aqua-complexes [(η-CMe)M(PP∗)(HO)][SbF] [M = Rh, Ir; PP∗ = (R)-Benphos, (R)-Cyphos, (2R,4R)-Norphos] catalyse the 1,3-dipolar cycloaddition reaction of nitrones with methacrylonitrile with perfect regioselectivity, low-to-perfect endo-selectivity and low-to-moderate enantioselectivity. The active species involved in the catalytic process, [(η-CMe)M(PP∗)(methacrylonitrile)][SbF], have been isolated and characterised as mixtures of the (S)- and (R)-at-metal epimers. NMR measurements of these mixtures indicated that the (R)-isomers epimerise to the corresponding (S) counterparts. The molecular structure of the rhodium complex (S,R)-[(η-CMe)Rh{(R)-Benphos}(methacrylonitrile)][SbF] has been determined by X-ray diffraction methods. Diastereomerically pure (S,R)-[(η-CMe)Rh(PP∗)(methacrylonitrile)][SbF] compounds catalyse stoichiometrically the above mentioned dipolar cycloaddition reaction with up to 90% enantiomeric excess, thus indicating the influence of the metal handedness on the catalytic stereochemical outcome. Catalysts can be recycled up to three times without a significant loss of either activity or selectivity.We thank the Ministerio de Economía y Competitividad, Spain and European Social Fund (Grants CTQ2012-32095, CTQ2015-66079-P and CONSOLIDER INGENIO-2010 CSD2006-0015), European Union and Gobierno de Aragón and European Social Fund (Grupo Consolidado: Catalizadores Organometálicos Enantioselectivos), European Union for financial support. A.A. thanks the IUCH for a grant.Peer Reviewe

Asymmetric 1,3-dipolar cycloaddition reactions between enals and nitrones catalysed by half-sandwich rhodium or iridium diphosphane complexes

The aqua complexes [(η5-C5Me5)M(PP*)(H2O)][SbF6]2 (M = Rh, Ir; PP* = chiral diphosphane) have been tested as catalysts for the asymmetric 1,3-dipolar cycloaddition of nitrones to α,β-unsaturated aldehydes. Quantitative conversions with very high regioselectivity, perfect endo selectivity and excellent enantioselectivity (up to 99% ee) were achieved. The stereochemical outcome was analyzed on the basis of the stereoelectronic properties of the intermediate enal complexes of the formula [(η5-C5Me5)M(PP*)(enal)][SbF6]2.We thank the Ministerio de Economía y Competitividad of Spain (CTQ2012-32095) and Gobierno de Aragón (Grupo Consolidado: Catalizadores Organometálicos Enantioselectivos) for financial support. A. A. acknowledges IUCH for a grant. R. R. acknowledges CSIC and European Social Fund for a JAE grant. M. C. acknowledges Gobierno de Aragón and CSIC for a DGA grant.Peer Reviewe

[RhCl(CO)(PPh3)]2. A precursor for the synthesis of cationic rhodium complexes with nitrogen donor ligands

The use of [RhCl(CO)(PPh3)]2 as a precursor for the synthesis of complexes of the types [Rh(CO)L2(PPh3)]A (A = [ClO4]− or [BPh4]−; L = pyridine type ligand) and [Rh(CO)(L-L)(PPh3)]A (A = [ClO4]− or [BPh4]−; L-L = bidentate nitrogen donor) and the preparation of several complexes of the types [Rh(CO)L(PPh3){P(p-RC6H4)3}]BPh4 and [Rh(CO)(phen)(PPh3){P(p-RC6H4)3}]A (A = [ClO4]− or [BPh4]−; R = H or Me) is described.Peer reviewe