Protecting-group-free site-selective reactions in a metal–organic framework reaction vessel

Site-selective organic transformations are commonly required in the synthesis of complex molecules. By employing a bespoke metal-organic framework (MOF, 1·[Mn(CO)3N3]), in which coordinated azide anions are precisely positioned within 1D channels, we present a strategy for the site-selective transformation of dialkynes into alkyne-functionalized triazoles. As an illustration of this approach, 1,7-octadiyne-3,6-dione stoichiometrically furnishes the mono-“click” product N-methyl-4-hex-5’-ynl-1’,4’dione-1,2,3-triazole with only trace bis-triazole side-product. Stepwise insights into conversions of the MOF reaction vessel were obtained by X-ray crystallography, demonstrating that the reactive sites are “isolated” from one another. Single-crystal to singlecrystal transformations of the Mn(I)-metalated material 1·[Mn(CO)3(H2O)]Br to the corresponding azide species 1·[Mn(CO)3N3] with sodium azide, followed by a series of [3+2] azide-alkyne cycloaddition reactions, are reported. The final liberation of the “click” products from the porous material is achieved by N-alkylation with MeBr, regenerating starting MOF 1·[Mn(CO)3(H2O)]Br, and the organic products characterized by NMR spectroscopy and mass spectrometry. Once the dialkyne length exceeds the azide separation, site selectivity is lost, confirming the critical importance of isolated azide moieties for this strategy. We postulate that carefully designed MOFs can act as physical protecting groups to facilitate other site-selective and chemoselective transformations

The genetic landscape and clinical spectrum of nephronophthisis and related ciliopathies

Nephronophthisis (NPH) is an autosomal-recessive ciliopathy representing one of the most frequent causes of kidney failure in childhood characterized by a broad clinical and genetic heterogeneity. Applied to one of the worldwide largest cohorts of patients with NPH, genetic analysis encompassing targeted and whole exome sequencing identified disease-causing variants in 600 patients from 496 families with a detection rate of 71%. Of 788 pathogenic variants, 40 known ciliopathy genes were identified. However, the majority of patients (53%) bore biallelic pathogenic variants in NPHP1. NPH-causing gene alterations affected all ciliary modules defined by structural and/or functional subdomains. Seventy six percent of these patients had progressed to kidney failure, of which 18% had an infantile form (under five years) and harbored variants affecting the Inversin compartment or intraflagellar transport complex A. Forty eight percent of patients showed a juvenile (5-15 years) and 34% a late-onset disease (over 15 years), the latter mostly carrying variants belonging to the Transition Zone module. Furthermore, while more than 85% of patients with an infantile form presented with extra-kidney manifestations, it only concerned half of juvenile and late onset cases. Eye involvement represented a predominant feature, followed by cerebellar hypoplasia and other brain abnormalities, liver and skeletal defects. The phenotypic variability was in a large part associated with mutation types, genes and corresponding ciliary modules with hypomorphic variants in ciliary genes playing a role in early steps of ciliogenesis associated with juvenile-to-late onset NPH forms. Thus, our data confirm a considerable proportion of late-onset NPH suggesting an underdiagnosis in adult chronic kidney disease

Dexamethasone Use and Mortality in Hospitalized Patients with Coronavirus Disease 2019: a Multicenter Retrospective Observational Study

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Triazolium-containing metal-organic frameworks: Control of catenation in 2-D Copper(II) paddlewheel structures

Paper accepted for publication 6th November 2012One approach to exploit MOFs as heterogeneous catalyst platforms requires the development of materials containing groups that can be utilised to anchor a catalytic moiety into the links within the structure. Here we report the synthesis of the first integrated triazolium-containing MOF linker and the first MOFs containing linkers of this type. 1,4-Bis(4-benzoic acid)-1-methyl-1H-1,2,3-triazolium chloride, H₂L1ᴹᵉ, was synthesised in three steps by a 'Click' reaction of methyl 4-ethynylbenzoate with methyl 4-azidobenzoate, methylation using methyl triflate, followed by ester hydrolysis in overall 74% yield. The equivalent neutral triazole precursor, 1,4-bis(4-benzoic acid)-1H-1,2,3-triazole hydrochloride, H₂L1(HCl), was also prepared and a comparison of the chemistry with Zn(NO₃)2·6H₂O and Cu(NO₃)₂·3H₂O is presented. [Zn(L1)₂(H₂O)₂] is a 2-D MOF with infinite chains of zinc carboxylates bridged by L1, while an equivalent structure is not observed for L1ᴹᵉ. In turn, two catenation isomers of [Cu₂(DMF)2(L1ᴹᵉ)2](NO3)₂ were isolated from a single reaction of L1ᴹᵉ and Cu(NO₃)₂·3H₂O. The α-form, a close-packed 3-fold interpenetrated structure, was obtained from reactions undertaken in the presence of nitric acid or at lower temperatures, while undertaking the reaction at higher temperatures leads to a predominance of the 2-fold interpenetrated and potentially porous β-form of the structure. The work presented provides further support for the use of reaction conditions to control interpenetration and additional evidence that charge on structurally similar ligands can drastically alter the types of structures that are accessible due to the requirements for charge balance in the final product.Alexandre M. Burgun, Christian J. Doonan, and Christopher J. Sumb

Synthesis, isomerisation and biological properties of mononuclear ruthenium complexes containing the bis[4(4 '-methyl-2,2 '-bipyridyl)]-1,7-heptane ligand

A series of mononuclear ruthenium(II) complexes containing the tetradentate ligand bis[4(4’-methyl-2,2’- bipyridyl)]-1,7-heptane have been synthesised and their biological properties examined. In the synthesis of the [Ru(phen’)(bb7)]2+ complexes (where phen’ = 1,10-phenanthroline and its 5-nitro-, 4,7-dimethyland 3,4,7,8-tetramethyl- derivatives), both the symmetric cis-α and non-symmetric cis-β isomers were formed. However, upon standing for a number of days (or more quickly under harsh conditions) the cis-β isomer converted to the more thermodynamically stable cis-α isomer. The minimum inhibitory concentrations (MIC) and the minimum bactericidal concentrations (MBC) of the ruthenium(II) complexes were determined against six strains of bacteria: Gram-positive Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA); and the Gram-negative Escherichia coli (E. coli) strains MG1655, APEC, UPEC and Pseudomonas aeruginosa (P. aeruginosa). The results showed that the [Ru(5-NO2phen)- (bb7)]2+ complex had little or no activity against any of the bacterial strains. By contrast, for the other cisα-[Ru(phen’)(bb7)]2+ complexes, the antimicrobial activity increased with the degree of methylation. In particular, the cis-α-[Ru(Me4phen)(bb7)]2+ complex showed excellent and uniform MIC activity against all bacteria. By contrast, the MBC values for the cis-α-[Ru(Me4phen)(bb7)]2+ complex varied considerably across the bacteria and even within S. aureus and E. coli strains. In order to gain an understanding of the relative antimicrobial activities, the DNA-binding affinity, cellular accumulation and water–octanol partition coefficients (log P) of the ruthenium complexes were determined. Interestingly, all the [Ru(phen’)- (bb7)]2+ complexes exhibited stronger DNA binding affinity (Ka ≈ 1 × 107 M−1 ) than the well-known DNAintercalating complex [Ru(phen)2(dppz)]2+ (where dppz = dipyrido[3,2-a:2’,3’-c]phenazine)

Oxidative activation of iron- and ruthenium-alkynyl complexes : toward square-shaped molecules with four redox-active metal centres.

The synthesis of square molecules containing four redox-active metal centres and two positive charges which would be interesting as potential candidates for molecular Quantum-dot Cellular Automata (QCA) models constitutes the aim of this thesis. In this new paradigm, the binary information is encoded in the charge configuration of the QCA cell, and in the case of a molecular QCA, in the charge configuration of a single molecule. In order to synthesise such molecules with metal centres of general formula M(PP)Cp’ [M = Fe, Ru; PP = dppe, (PPh₃)₂; Cp’ = Cp, Cp*], new synthetic methods have been developed. By chemically oxidising mono- or bi-metallic alkynyl complexes, radical coupling can occur, mainly depending on the nature of the metal (Fe or Ru) and the length of the carbon chain (C₂, C₄ or C₆), to give dimers with original geometry. Therefore, this thesis describes the oxidation studies of iron- and ruthenium-alkynyl complexes containing short (C₂) to long carbon chains (C₆), and the characterisations of the oxidised products. The reactivity of the mononuclear 17-electron species [Ru(C≡CR)(PPh₃)₂Cp]•+ (16, R = Ph; 19, R = Tol) and [Fe(C≡CC≡CR)(dppe)Cp*]•+ (2a, R = Ph; 2b R = Tol) was investigated, dimerisation occurring in both cases. Intermolecular radical coupling of 16•+ afforded a linear dimer by coupling at the C[subscript]β and C[subscript]para positions, whereas dimerisation of 2•+ gives a single dicationic complex [27][PF₆]₂ containing a squared C₄ ring centre and two Fe(dppe)Cp* units. The reactivity of the bimetallic 35-electron species [{Cp’(dppe)M}(C≡CC≡CC≡C) {M(dppe)Cp’}]•+ (M = Fe, Ru; Cp’ = Cp, Cp*) was also investigated. The mixed-valence systems containing the M(dppe)Cp* (M = Fe, Ru) fragments were revealed to be stable and isolable: the first crystal structures of mixed-valence complexes with a carbon chain longer than C4 were resolved for [{Cp*(dppe)Fe}₂(μ-C≡CC≡CC≡C)]PF₆ [30]PF₆ and [{Cp*(dppe)Fe}(C≡CC≡CC≡C){Ru(dppe)Cp*}]PF₆ [34]PF₆. Electronic delocalisation in these stable mixed-valence complexes, between the two metal centres and through the C₆ bridge, was revealed to be strong which was unexpected for the unsymmetrical system [34]PF₆. In contrast, the mixed-valence systems containing the Ru(dppe)Cp fragment were not stable at room temperature and dimerised to afford dicationic square-shaped tetrametallic complexes with a C₄ ring centre. Two unsymmetrical dimers were characterised: one containing four Ru(dppe)Cp centres [43][PF₆]₂ and the other containing two Ru(dppe)Cp and two Fe(dppe)Cp* fragments [44][PF₆]₂. Compound [43][PF₆]₂ has been fully characterised and the positive charge revealed to be fully delocalised over the whole molecule. Even if unsymmetrical, these molecules are interesting for being potential molecular QCA models. It has been shown that TCNQ acts as an oxidising agent for iron- and ruthenium-alkynyl complexes. The organometallic 17-e species generated further react by coupling between the cationic and anionic radical [TCNQ]•- to give specifically TCNQ adducts. These new complexes which contain two electrophores possess unique properties. The σ-linked electron donor organometallic centre and the organic electron withdrawing group via an alkyndiyl bridge allow intramolecular charge transfer. The X-ray crystal structure analyses, electrochemistry and UV-Vis spectroscopy have been investigated and reveal the interesting properties of these molecules.Thesis (Ph.D.) -- University of Adelaide, School of Chemistry and Physics, 201

Activation de complexes alcynyles à base de fer et de ruthénium par oxydation mono-électronique (vers des molécules carrées à quatre centres métalliques électro -actifs)

RENNES1-BU Sciences Philo (352382102) / SudocSudocFranceF

Design of an Ontology-Based Triage System for Patients with Chronic Pain

International audienceObjective: Waiting time for a consultation for chronic pain is a widespread health problem. This paper presents the design of an ontology use to assess patients referred to a consultation for chronic pain. Methods: We designed OntoDol, an ontology of pain domain for patient triage based on priority degrees. Terms were extracted from clinical practice guidelines and mapped to SNOMED-CT concepts through the Python module Owlready2. Selected SNOMED-CT concepts, relationships, and the TIME ontology, were implemented in the ontology using Protégé. Decision rules were implemented with SWRL. We evaluated OntoDol on 5 virtual cases. Results: OntoDol contains 762 classes, 92 object properties and 18 SWRL rules to assign patients to 4 categories of priority. OntoDol was able to assert every case and classify them in the right category of priority. Conclusion: Further works will extend OntoDol to other diseases and assess OntoDol with real world data from the hospital

Reactions of 7,7,8,8-tetracyanoquinodimethane (TCNQ) with alkynyl-iron or -ruthenium complexes : synthesis of Ru{CC(CN)=C6H4=C(CN)2}(PPh3)2Cp, a new donor acceptor molecular array

International audienceReactions of 7,7,8,8-tetracyanoquinodimethane (TCNQ) with the alkynyl-iron and ruthenium complexes [M](C≡CR) {[M] = Fe(dppe)Cp*, Ru(PPh3)2Cp; R = H, Ph} are described. The iron complex Fe(C≡CPh)(dppe)Cp* (2a) is oxidized by TCNQ to give the kinetically stable salt [2a*+][TCNQ]*- . Displacement of [TCNQ]*- is achieved by ionic metathesis upon addition of KPF6 to produce [2a*+]PF6. In contrast, Fe(C≡CH)(dppe)Cp* (2b) reacted with TCNQ to give a mixture of compounds containing Fe(=C=CH2)(dppe)Cp* (3a), {Fe(dppe)Cp*}2(μ-C=CHCH=C) (3b), and the zwitterionic complex Fe+{=C=CHC(CN)2C6H4C-(CN)2}(dppe)Cp* (3c). In contrast, the reaction of TCNQ with Ru(C≡CR)(PPh3)2Cp (4a, R = Ph; 4b, R = H) gave selectively the zwitterionic vinylidenes Ru+{=C=CRC(CN)2C6H4C-(CN)2}(PPh3)2Cp (5a, R = Ph; 5b, R = H), in which the Ru centres are positively charged and the counter-anion is located on the further C(CN)2 group. On heating 5b, elimination of HCN affords Ru{C≡CC(CN)=C6H4=C(CN)2}(PPh3)2Cp (1), while similar treatment of 5a gives Ru{η3-C(CN)2CPh=C6H4=C(CN)2}(PPh3)Cp (6) with loss of PPh3. X-ray structures of 1, 5a, and 6, cyclic voltammetry, and UV-vis spectroscopy of 1 provided evidence for the electronic structures of the new complexes

Correction to From Molecular Wires to Molecular Resistors: TCNE, a Class-III/Class-II Mixed-Valence Chemical Switch

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