Dissociation of HNO3 in water revisited: experiment and theory.

Nitric acid dissociation in water is studied as a function of concentration, employing experimental techniques (1H NMR spectroscopy and calorimetry), quantum chemical methods (B3LYP and PBE functionals for molecular clusters) and molecular dynamics simulations (the PBE-D3 functional for solutions under periodic boundary conditions). The extent of dissociation, via proton transfer to a neighboring water molecule, as a function of concentration is studied computationally for molecular nitric acid clusters HNO3(H2O)x (x = 1-8), as well as periodic liquids (HNO3 mole fractions of 0.19 and 0.5, simulated at T = 300 K and 450 K). Despite the simple nature of these structural models, their computed and simulated average 1H chemical shifts compare well with the experimental measurements in this study. Finally, the measured and calculated chemical shifts have shown reasonable relationships with the enthalpy change upon mixing of this binary complex.

Synthesis of Tetra-Substituted 3-Hydroxyphthalide Esters by Isothiourea-Catalysed Acylative Dynamic Kinetic Resolution.

A general and highly enantioselective method for the preparation of tetra-substituted 3-hydroxyphthalide esters via isothiourea-catalysed acylative dynamic kinetic resolution (DKR) is reported. Using (2S,3R)-HyperBTM (5 mol %) as the catalyst, the scope and limitations of this methodology have been extensively probed, with high enantioselectivity and good to excellent yields observed (>40 examples, up to 99 %, 99 : 1 er). Substitution of the aromatic core within the 3-hydroxyphthalide skeleton, as well as aliphatic and aromatic substitution at C(3), is readily tolerated. A diverse range of anhydrides, including those from bioactive and pharmaceutically relevant acids, can also be used. The high enantioselectivity observed in this DKR process has been probed computationally, with a key substrate heteroatom donor O⋅⋅⋅acyl-isothiouronium interaction identified through DFT analysis as necessary for enantiodiscrimination.

Electrochemical Activation Applied to Perovskite Titanate Fibers to Yield Supported Alloy Nanoparticles for Electrocatalytic Application.

Active bi-metallic nanoparticles are of key importance in catalysis and renewable energy. Here, the in situ formation of bi-metallic nanoparticles is investigated by exsolution on 200 nm diameter perovskite fibers. The B-site co-doped perovskite fibers display a high degree of exsolution, decorated with NiCo or Ni3 Fe bi-metallic nanoparticles with average diameter about 29 and 35 nm, respectively. The perovskite fibers are utilized as cathode materials in pure CO2 electrolysis cells due to their redox stability in the CO/CO2 atmosphere. After in situ electrochemical switching, the nanoparticles exsolved from the perovskite fiber demonstrate an enhanced performance in pure CO2 electrolysis. At 900 °C, the current density of solid oxide electrolysis cell (SOEC) with 200 µm YSZ electrolyte supported NiFe doped perovskite fiber anode reaches 0.75 Acm-2 at 1.6 V superior to the NiCo doped perovskite fiber anode (about 1.5 times) in pure CO2 . According to DFT calculations (PBE-D3 level) the superior CO2 conversion on NiFe compared to NiCo bi-metallic species is related to an enhanced driving force for C-O cleavage under formation of CO chemisorbed on the nanoparticle and a reduced binding energy of CO required to release this product.

Outcomes of octogenarians and nonagenarians with Pseudomonas aeruginosa bacteremia: a multicenter retrospective study.

BACKGROUND: P. aeruginosa bacteremia is a common and severe infection carrying high mortality in older adults. We aimed to evaluate outcomes of P. aeruginosa bacteremia among old adults (≥ 80 years). METHODS: We included the 464/2394 (19%) older adults from a retrospective multinational (9 countries, 25 centers) cohort study of individuals hospitalized with P. aeruginosa bacteremia. Bivariate and multivariable logistic regression models were used to evaluate risk factors for 30-day mortality among older adults. RESULTS: Among 464 adults aged ≥ 80 years, the mean age was 84.61 (SD 3.98) years, and 274 (59%) were men. Compared to younger patients, ≥ 80 years adults had lower Charlson score; were less likely to have nosocomial acquisition; and more likely to have urinary source. Thirty-day mortality was 30%, versus 27% among patients 65-79 years (n = 894) and 25% among patients < 65 years (n = 1036). Multivariate analysis for predictors of mortality among patients ≥ 80 years, demonstrated higher SOFA score (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.23-1.51, p < 0.001), corticosteroid therapy (OR 3.15, 95% CI: 1.24-8.01, p = 0.016) and hospital acquired P. aeruginosa bacteremia (OR 2.30, 95% CI: 1.33-3.98, p = 0.003) as predictors. Appropriate empirical therapy within 24 h, type of definitive anti-pseudomonal drug, and type of regimen (monotherapy or combination) were not associated with 30-day mortality. CONCLUSIONS: In older adults with P. aeruginosa bacteremia, background conditions, place of acquisition, and disease severity are associated with mortality, rather than the antimicrobial regimen. In this regard, preventive efforts and early diagnosis before organ failure develops might be beneficial for improving outcomes.

Phosphine and Selenoether peri-Substituted Acenaphthenes and Their Transition-Metal Complexes: Structural and NMR Investigations.

A series of peri-substituted acenaphthene-based phosphine selenoether bidentate ligands Acenap(iPr2P)(SeAr) (L1-L4, Acenap = acenaphthene-5,6-diyl, Ar = Ph, mesityl, 2,4,6-trisopropylphenyl and supermesityl) were prepared. The rigid acenaphthene framework induces a forced overlap of the phosphine and selenoether lone pairs, resulting in a large magnitude of through-space 4JPSe coupling, ranging from 452 to 545 Hz. These rigid ligands L1-L4 were used to prepare a series of selected late d-block metals, mercury, and borane complexes, which were characterized, including by multinuclear NMR and single-crystal X-ray diffraction. The Lewis acidic motifs (BH3, Mo(CO)4, Ag+, PdCl2, PtCl2, and HgCl2) bridge the two donor atoms (P and Se) in all but one case in the solid-state structures. Where the bridging motif contained NMR-active nuclei (11B, 107Ag, 109Ag, 195Pt, and 199Hg), JPM and JSeM couplings are observed directly, in addition to the altered JPSe in the respective NMR spectra. The solution NMR data are correlated with single-crystal diffraction data, and in the case of mercury(II) complexes, they are also correlated with the solid-state NMR data and coupling deformation density calculations. The latter indicate that the through-space interaction dominates in free L1, while in the L1HgCl2 complex, the main coupling pathway is via the metal atom and not through the carbon framework of the acenaphthene ring system.

13C pNMR shifts of MOFs based on Cu(II)-paddlewheel dimers - DFT predictions for spin-1/2 defects.

We present DFT predictions (CAM-B3LYP/II level) for the paramagnetic Nuclear Magnetic Resonance (pNMR) spectra of small molecular models based on the Cu(II)-paddlewheel dimer motif that is present in metal-organic frameworks (MOFs, notably the HKUST and STAM families). We explore potential point defects with spin-1/2 discovered through electron paramagnetic resonance (EPR) experiments. We consider defects through substitution of one Cu(II) centre in the dimer with protons, or through one-electron reduction, affording a mixed-valence dimer. While most of the defects have predicted pNMR shifts at room temperature in the range of those for the non-defective MOFs, their detection and assignment should be possible based on their distinct temperature dependence.

Towards Computational Modeling of Ligand Binding to the ILPR G-Quadruplex.

Using a combination of unconstrained and constrained molecular dynamics simulations, we have evaluated the binding affinities between two porphyrin derivatives (TMPyP4 and TEGPy) and the G-quadruplex (G4) of a DNA fragment modeling the insulin-linked polymorphic region (ILPR). Refining a well-established potential of mean force (PMF) approach to selections of constraints based on root-mean-square fluctuations results in an excellent agreement between the calculated and observed absolute free binding energy of TMPyP4. The binding affinity of IPLR-G4 toward TEGPy is predicted to be higher than that toward TMPyP4 by 2.5 kcal/mol, which can be traced back to stabilization provided by the polyether side chains of TMPyP4 that can nestle into the grooves of the quadruplex and form hydrogen bonds through the ether oxygen atoms. Because our refined methodology can be applied to large ligands with high flexibility, the present research opens an avenue for further ligand design in this important area.

Constrained Phosphine Chalcogenide Selenoethers Supported by peri-Substitution.

A series of phosphorus and selenium peri-substituted acenaphthene species with the phosphino group oxidized by O, S, and Se has been isolated and fully characterized, including by single-crystal X-ray diffraction. The P(V) and Se(II) systems showed fluxional behavior in solution due to the presence of two major rotamers, as evidenced with solution NMR spectroscopy. Using Variable-Temperature NMR (VT NMR) and supported by DFT (Density Functional Theory) calculations and solid-state NMR, the major rotamers in the solid and in solution were identified. All compounds showed a loss of the through-space JPSe coupling observed in the unoxidized P(III) and Se(II) systems due to the sequestration of the lone pair of the phosphine, which has been previously identified as the major contributor to the coupling pathway.

Rational Design of a Facially Coordinating P,N,N Ligand for Manganese-Catalysed Enantioselective Hydrogenation of Cyclic Ketones.

DFT calculations on the full catalytic cycle for manganese catalysed enantioselective hydrogenation of a selection of ketones have been carried out at the PBE0-D3PCM //RI-BP86PCM level. Mn complexes of an enantiomerically pure chiral P,N,N ligand have been found to be most reactive when adopting a facial coordination mode. The use of a new ligand with an ortho-substituted dimethylamino-pyridine motif has been calculated to completely transform the levels of enantioselectivity possible for the hydrogenation of cyclic ketones relative to the first-generation Mn catalysts. In silico evaluation of substrates has been used to identify those likely to be reduced with high enantiomer ratios (er), and others that would exhibit less selectivity; good agreements were then found in experiments. Various cyclic ketones and some acetophenone derivatives were hydrogenated with er's up to 99 : 1.

Synthesis of Polyethyleneimines from the Manganese-Catalysed Coupling of Ethylene Glycol and Ethylenediamine.

Polyethyleneimines find many applications in products such as detergents, adhesives, cosmetics, and for processes such as tissue culture, gene therapy, and CO2 capture. The current state-of-the-art technology for the production of the branched polyethyleneimines involves aziridine feedstock which is a highly toxic, volatile and mutagenic chemical and raises significant concern to human health and environment. We report here a novel method for the synthesis of branched polyethyleneimine derivative from ethylene glycol and ethylenediamine which are much safer, environmentally benign, commercially available and potentially renewable feedstock. The polymerisation reaction is catalysed by a complex of an earth-abundant metal, manganese and liberates H2 O as the only by-product. Our mechanistic studies using a combination of DFT computation and experiment suggest that the reaction proceeds by the formation and subsequent hydrogenation of imine intermediates.

Computational Insights into the Catalytic Mechanism of Is-PETase: An Enzyme Capable of Degrading Poly(ethylene) Terephthalate.

Is-PETase has become an enzyme of significant interest due to its ability to catalyse the degradation of polyethylene terephthalate (PET) at mesophilic temperatures. We performed hybrid quantum mechanics and molecular mechanics (QM/MM) at the DSD-PBEP86-D3/ma-def2-TZVP/CHARMM27//rev-PBE-D3/dev2-SVP/CHARMM level to calculate the energy profile for the degradation of a suitable PET model by this enzyme. Very low overall barriers are computed for serine protease-type hydrolysis steps (as low as 34.1 kJ mol-1 ). Spontaneous deprotonation of the final product, terephthalic acid, with a high computed driving force indicates that product release could be rate limiting.

Transmission of spin-polarization by π-orbitals: an approach to assessing its effect on NMR spin-spin coupling and EPR hyperfine structure.

A new approach to assessing the effect of the transmission of spin-polarization by π-orbitals (π-TSP) is presented. In order to switch off the π-TSP effect, we artificially average the α- and ß-densities of the valence π-orbitals when calculating the exchange-correlation contribution to the Fock matrix in the unrestricted Kohn-Sham framework. The π-TSP effect is then evaluated as the difference between the results obtained with switched-on and switched-off options. This approach is applied to estimate the π-TSP effect on the Fermi-contact contribution to spin-spin couplings and EPR hyperfine structure coupling constants. The π-TSP effect on the distribution of spin-density, spin-spin coupling pathways and pathways of EPR hyperfine couplings is demonstrated for benzene, naphthalene, 1,3,5,7,9-decapentaene and the 1,3,5,7,9-decapentaen-1-yl radical. The sign alternation of the spin-polarization transmitted by π-orbitals is explained in a theoretical framework based on perturbation theory. However, the delocalized nature of the π-system can interfere with the sign alternation in certain cases, two of which - the cyclobutadiene dication and the cyclooctatetraene dication - are examined, and an explanation for which is provided.

Sulfur and Phosphorus Oxyacid Radicals.

We report a computational study of the little-studied neutral bisulfite, bisulfate, dihydro-phosphite, and dihydro-phosphate radicals (HSOx•, H2POx•, x = 3,4), calling special attention to their various tautomeric structures together with pKa values estimated from the Gibbs free energies of their dissociations (at the G4 and CAM-B3LYP levels of density functional theory). The energetics of microhydration clusters with up to four water molecules for the S-based species and up to eight water molecules for the P-based species were investigated. The number of microhydrating water molecules needed to induce spontaneous de-protonation is found to correlate the acid strength of each radical. According to the computed Gibbs free reaction and activation energies, S- and P-centered radicals preferentially add to the double bond of propene (a lipid model), whereas the O-centered radical tautomers prefer H-abstraction. The likely downstream reactions of these radicals in biological media are discussed.

Microbiota-associated Risk Factors for Clostridioides difficile Acquisition in Hospitalized Patients: A Prospective, Multicentric Study.

BACKGROUND: Asymptomatic C. difficile colonization is believed to predispose to subsequent C. difficile infection (CDI). While emerging insights into the role of the commensal microbiota in mediating colonization resistance against C. difficile have associated CDI with specific microbial components, corresponding prospectively collected data on colonization with C. difficile are largely unavailable. METHODS: C. difficile status was assessed by GDH EIA and real-time PCR targeting the toxin A (tcdA) and B (tcdB) genes. 16S V3 and V4 gene sequencing results from fecal samples of patients tested positive for C. difficile were analyzed by assessing alpha and beta diversity, LefSe, and the Piphillin functional inference approach to estimate functional capacity. RESULTS: 1506 patients were recruited into a prospective observational study (DRKS00005335) upon admission into one of five academic hospitals. 936 of them provided fecal samples on admission and at discharge and were thus available for longitudinal analysis. Upon hospital admission, 5.5% (83/1506) and 3.7% (56/1506) of patients were colonized with toxigenic (TCD) and non-toxigenic C. difficile (NTCD), respectively. During hospitalization, 1.7% (16/936) acquired TCD. Risk factors for acquisition of TCD included pre-existing lung diseases, lower GI endoscopy and antibiotics. Species protecting against hospital-related C. difficile acquisition included Gemmiger spp., Odoribacter splanchnicus, Ruminococcus bromii and other Ruminococcus spp. Metagenomic pathway analysis identified steroid biosynthesis as the most underrepresented metabolic pathway in patients who later acquire C. difficile colonization. CONCLUSIONS: Gemmiger spp., Odoribacter splanchnicus, Ruminococcus bromii and other Ruminococci were associated with a decreased risk of C. difficile acquisition. CLINICAL TRIALS REGISTRATION: DRKS00005335.

Combination versus monotherapy as definitive treatment for Pseudomonas aeruginosa bacteraemia: a multicentre retrospective observational cohort study.

BACKGROUND: Pseudomonas aeruginosa bacteraemia is a common and serious infection. No consensus exists regarding whether definitive combination therapy is superior to monotherapy. We aimed to evaluate the impact of combination therapy on mortality. METHODS: This was a multicentre retrospective study (nine countries, 25 centres), including 1277 patients with P. aeruginosa bacteraemia during 2009-15. We evaluated the association between ß-lactam plus aminoglycoside or quinolone combination therapy versus ß-lactam monotherapy and mortality. The primary outcome was 30 day all-cause mortality. Univariate and multivariate Cox regression analyses were conducted, introducing combination as a time-dependent variable. Propensity score was conducted to adjust for confounding for choosing combination therapy over monotherapy. RESULTS: Of 1119 patients included, 843 received definitive monotherapy and 276 received combination therapy (59% aminoglycoside and 41% quinolone). Mortality at 30 days was 16.9% (189/1119) and was similar between combination (45/276; 16.3%) and monotherapy (144/843; 17.1%) groups (P = 0.765). In multivariate Cox regression, combination therapy was not associated with reduced mortality (HR 0.98, 95% CI 0.64-1.53). No advantage in terms of clinical failure, microbiological failure or recurrent/persistent bacteraemia was demonstrated using combination therapy. Likewise, adverse events and resistance development were similar for the two regimens. CONCLUSIONS: In this retrospective cohort, no mortality advantage was demonstrated using combination therapy over monotherapy for P. aeruginosa bacteraemia. Combination therapy did not improve clinical or microbiological failure rates, nor affect adverse events or resistance development. Our finding of no benefit with combination therapy needs confirmation in well-designed randomized controlled trials.

Prevotella illustrans sp. nov., derived from human oropharyngeal abscess puncture fluid.

An obligately anaerobic strain, designated as A2931T, was isolated from oropharyngeal abscess puncture fluid of a patient sampled during routine care at a hospital and further characterized both phenotypically, biochemically and genotypically. This Gram-negative rod-shaped bacterium was moderately saccharolytic and proteolytic. Phylogenetic analyses of full-length 16S rRNA gene and whole-genome sequences revealed it to be best placed in the genus Prevotella, but to be only comparatively distantly related to recognized species, with the closest relationship to Prevotella baroniae (average nucleotide identity and digital DNA-DNA hybridization values both well below the generally accepted thresholds). Strain A2931T had a genomic DNA G+C content of 47.7 mol%. Its most abundant cellular long-chain fatty acids were anteiso-C15 : 0, iso-C15 : 0 and C16 : 0. Taken together, this polyphasic data suggests strain A2931T to represent a novel species within the genus Prevotella, for which the name Prevotella illustrans sp. nov. is proposed. The type strain is A2931T (=DSM 108028T=CCOS 1232T=CCUG 72806T). Interestingly, we found strain A2931T to correspond to the oral taxon Prevotella HMT-820 in the Human Oral Microbiome Database, as supported by overall genome relatedness index analyses >99 %. Thus, our work not only closes one of the gaps of knowledge about hitherto unnamed species isolated from humans, but also will facilitate identification of this taxon both in the clinical microbiology context and in research alike.

Eikenella glucosivorans sp. nov., isolated from a human throat swab, and emendation of the genus Eikenella to include saccharolytic species.

A novel species within the genus Eikenella is described, based on the phenotypical, biochemical and genetic characterization of a strain of a facultatively anaerobic, Gram-negative rod-shaped bacterium. Strain S3360T was isolated from the throat swab of a patient sampled during routine care at a hospital. Phylogenetic analyses (full-length 16S rRNA gene and whole-genome sequences) placed the strain in the genus Eikenella, separate from all recognized species but with the closest relationship to Eikenella longinqua (NML 02-A-017T). Eikenella is one of the genera in the HACEK group known to be responsible for rare cases of endocarditis in humans. Until the recent descriptions of Eikenella exigua, Eikenella halliae and Eikenella longinqua, Eikenella corrodens had been the only validly published species in this genus since its description as Bacteroides corrodens in 1958. Unlike these species, strain S3360T is able to metabolize carbohydrates (glucose). The average nucleotide identities of strain S3360T with E. longinqua (NML 02-A-017T) and E. corrodens (NCTC 10596T), the type species of the genus, were 90.5 and 84.7 %, respectively, and the corresponding genome-to-genome distance values were 41.3 and 29.0 %, respectively. The DNA G+C content of strain S3360T was 58.4 mol%. Based on the phenotypical, biochemical and genetic findings, strain S3360T is considered to represent a novel species within the genus Eikenella, for which the name Eikenella glucosivorans sp. nov. is proposed. The type strain is S3360T (DSM 110714T=CCOS 1935T=CCUG 74293T). In addition, an emendation of the genus Eikenella is proposed to include species which are saccharolytic.

Parvimonas parva sp. nov., derived from a human genito-urinary lesion.

A strain of obligately anaerobically growing Gram-positive cocci was isolated from a human genito-urinary sample and characterized by a polyphasic approach. Analyses of 16S rRNA gene and whole-genome sequences of this strain S3374T indicated that it belonged to the genus Parvimonas. Overall genome relatedness index calculations confirmed it to be phylogenetically distinct from Parvimonas micra (NCTC 11808T) as its most closely related species with standing in nomenclature, with average nucleotide identity and genome-to-genome distance values of 85.8 and 30.2 %, respectively. Biochemically, strain S3374T was strongly proteolytic and can be differentiated from P. micra (DSM 20468T) by absence of phosphatase activity. The DNA G+C content of strain S3374T was 28.6 mol%. Based on the phenotypical, biochemical and genetic findings, strain S3374T is considered to represent a novel species within the genus Parvimonas, for which the name Parvimonas parva sp. nov. is proposed. The type strain is S3374T (=DSM 110786T=CCOS 1934T=CCUG 74294T). This description adds strain S3374T as a second species to the genus Parvimonas which has so far been monotypic. While the type strain of this genus, P. micra, has a long standing in nomenclature and its role in human health and disease has been studied to some extent, this description of the proposed novel species represented by strain S3374T will allow microbiologists worldwide to identify isolates of P. parva sp. nov., a prerequisite for further investigation of its relevance in the clinical context and beyond.

Bridging (Thionylimido)metal Complexes.

We report the first examples of the thionylimido ligand acting as a µ2-bridging ligand between two transition-metal centers; using Cp2Ti(NSO)2, we describe bi- and tetrametallic systems.

Computational modelling of Pd-catalysed alkoxycarbonylation of alkenes and alkynes.

This perspective highlights the computational modelling of alkene and alkyne alkoxycarbonylation at palladium catalysts. We cover studies on Pd-catalysed alkoxycarbonylation of alkenes with bidentate diphosphine ligands, which reveal a hydride pathway is operating with an intermolecular alcoholysis step, where explicit solvation is mandatory to estimate the overall barriers correctly and model alcoholysis/copolymerisation selectivities. Subsequently, we discuss Pd-catalysed alkyne alkoxycarbonylation with P,N-chelating ligands, where an in situ base mechanism is operating involving ketene-type intermediates. We also discuss catalyst poisoning due to allene and designing a potential new catalyst tolerant towards allene poisoning.