Does perdeuteration increase the polarity of Janus face cycloalkanes?

Funding: Authors are grateful to the Chinese Scholarship Council for studentship (Z. F. and C. Y.) support and also the Scientific Research Project of Hubei Education Department (Q20211402) and the open project of Hubei Provincial Key Laboratory of Green Materials for Light Industry (202107B06) for financial support.Stimulated by a suggestion of the late Professor Jack D. Dunitz, that perdeuterated Janus face cycloalkanes may be more polar than their unlabelled forms, the deuterated isotopologue of all cis-1,2,3,4,5,6-hexafluorocyclohexane ([2H6]- 1a ) and all cis-1,2,3,4-tetrafluorocyclopentane ([2H6]- 3a ) were prepared. Computation at the B3LYP−D3 level indicated that [2H6]- 1a is not more polar than its protio form 1, however perdeuterated cyclopentane [2H6]- 3a may indeed be more polar than 3 , although the magnitude is predicted to be small. None-the-less retention time analysis on a reverse phase GC/MS column of an add-mix of 3 and [2H6]- 3a gave some indication that the per-deuterated isotopologue 3a was detected marginally before the unlabelled compound consistent with increased polarity associated with perdeuteration.Publisher PDFPeer reviewe

Structure and dynamics of iron pentacarbonyl

The dynamics of CO ligand scrambling in Fe(CO)5 has been investigated by linear infrared spectroscopy in supercritical xenon solution. The activation barrier for the Berry pseudorotation in Fe(CO)5 was determined experimentally to be Ea = 2.5 ± 0.4 kcal mol–1 by quantitative analysis of the temperature-dependent spectral line shape. This compares well with the range of Ea/(kcal mol–1) = 2.0 to 2.3 calculated by various DFT methods and the value of 1.6 ± 0.3 previously obtained from 2D IR measurements by Harris et al. ( Science 2008, 319, 1820). The involvement of Fe(CO)5···Xe interactions in the ligand scrambling process was tested computationally at the BP86-D3/AE2 level and found to be negligible

Organofluorine chemistry : difluoromethylene motifs spaced 1,3 to each other imparts facial polarity to a cyclohexane ring

This work was supported by the Engineering and Physical Sciences Research Council (EPSRC) and the European Research Council (ERC). The authors acknowledge the EPSRC National Mass Spectrometry Facility (Swansea). D.O’H. thanks the Royal Society for a Wolfson Research Merit Award.2,2-Dimethyl-5-phenyl-1,1,3,3-tetrafluororocyclohexane has been prepared and characterised as an example of a facially polarised cyclohexane containing 1,3 related CF2 groups. The dipolar nature of the ring arises from the axial orientation of two of the C-F bonds pointing in the same direction, and set by the chair conformation of the cyclohexane. This electrostatic profile is revealed experimentally both in the solid-state (X-ray) packing of the rings and by solution (NMR) in different solvents. A computationally derived electrostatic profile of this compound is consistent with a more electronegative and a more electropositive face of the cyclohexane ring. This placing of CF2 groups 1,3 to each other in a cyclohexane ring is introduced as a new design strategy which could be applicable to the preparation of polar hydrophobic cyclohexane motifs.Publisher PDFPeer reviewe

Effect of ligand backbone on the selectivity and stability of rhodium hydroformylation catalysts derived from phospholane-phosphites

We thank the Eastman Chemical Company for funding and permission to publish. M.B. thanks the School of Chemistry and EaStCHEM for support.A study on how ligand backbone structure has an impact on selectivity, rate, and catalyst stability of hydroformylation catalysts was prompted by some longer-term stability issues being discovered for a phospholane-phosphite with a [−CH2O−] backbone. A series of phospholane-phosphite ligands were synthesized. Catalysts made in situ from these ligands and [Rh(acac)(CO)2] were found to give iso-butanal selectivities up to 75% at temperatures between 75 and 105 °C: the latter being a benchmark for iso-selectivity in reactions conducted at industrially meaningful temperatures. A racemic rhodium complex of a bidentate phospholane-phosphite from a tropos-biphenol with an extended backbone showed unusually high stability at high temperatures, combined with even better iso-selectivity in propene hydroformylation relative to the original complex. A related ligand with an electron-withdrawing group maintained the unusually high stability and improved activity. Characterization of the precatalysts of type [RhH(CO)2(L)] was accomplished using in situ HPIR spectroscopy and backed up by density functional theory calculations (B3PW91-D3 level) and by NMR studies; the latter showed that the variation of the backbone also had a pronounced impact on the precatalyst structure. A key finding is that it is now possible to prepare phospholane-phosphite ligands that deliver high iso-butanal selectivity and that show no signs of degradation after several days even above typical reaction temperatures. In one stability test, several kilograms of aldehydes were produced with TOF and selectivity being consistent over several days.PostprintPeer reviewe

Artificial Metalloenzymes as Catalysts for Oxidative Lignin Degradation

We report novel artificial metalloenzymes (ArMs), containing tris­(pyridylmethyl)­amine (TPA), for the atom economic oxidation of lignin β-O-4 model compounds, using hydrogen peroxide. The protein scaffold alters the selectivity of the reaction from a low yielding cleavage reaction when using the parent Fe-tpa complex to a high yielding benzylic alcohol oxidation when using the complex incorporated into a protein scaffold, SCP-2L A100C. Engineering the protein scaffold to incorporate glutamic acid was found to improve the ArM activity, showing that rational design of the protein environment using metal binding amino acids can be a first step toward improving the overall activity of an artificial metalloenzyme

Ligand electronic fine-tuning and its repercussion on the photocatalytic activity and mechanistic pathways of the copper-photocatalysed aza-Henry reaction

A family of six structurally related heteroleptic copper(i) complexes of the form of [Cu(N^N)(P^P)]+ bearing a 2,9-dimethyl-1,10-phenanthroline diimine (N^N) ligand and a series of electronically tunable xantphos (P^P) ligands have been synthesized and their optoelectronic properties characterized. The reactivity of these complexes in the copper-photocatalyzed aza-Henry reaction of N-phenyltetrahydroisoquinoline was evaluated, while the related excited state kinetics were comprehensively studied. By subtlety changing the electron-donating properties of the P^P ligands with negligible structural differences, we could tailor the photoredox properties and relate them to the reactivity. Moreover, depending on the exited-state redox potential of the catalysts, the preferred mechanism can shift between reductive quenching, energy transfer and oxidative quenching pathways. A combined study of the structural modulation of copper(i) photocatalysts, optoelectronic properties and photocatalytic reactivity resulted in a clearer understanding of both the rational design of the photocatalyst and the complexity of competing photoinduced electron and energy transfer mechanisms. © The Royal Society of Chemistry

Corrigendum: Specifically increased rate of infections in children post measles in a high resource setting

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Specifically Increased Rate of Infections in Children Post Measles in a High Resource Setting

Objectives: Post-measles increased susceptibility to subsequent infections seems particularly relevant in low-resource settings. We tested the hypothesis that measles causes a specifically increased rate of infections in children, also in a high-resource setting. Methods: We conducted a retrospective cohort study on a large measles outbreak in Berlin, Germany. All children with measles who presented to hospitals in Berlin were included as cases, children with non-infectious and children with non-measles infectious diseases as controls. Repeat visits within 3 years after the outbreak were recorded. Results: We included 250 cases, 502 non-infectious, and 498 infectious disease controls. The relative risk for cases for the diagnosis of an infectious disease upon a repeat visit was 1.6 (95% CI 1.4–2.0, p < 0.001) vs. non-infectious and 1.3 (95% CI 1.1–1.6, p = 0.002) vs. infectious disease controls. 33 cases (27%), 35 non-infectious (12%) and 57 (18%) infectious disease controls presented more than three times due to an infectious disease (p = 0.01, and p = 0.02, respectively). This results in a relative risk of more than three repeat visits due to an infection for measles cases of 1.8 (95% CI 1.3–2.4, p = 0.01), and 1.4 (95% CI 1.0–1.9, p = 0.04), respectively. Conclusion: Our study demonstrates for the first time in a high-resource setting, that increased post-measles susceptibility to subsequent infections in children is measles-specific—even compared to controls with previous non-measles infections.Peer Reviewe

The Intraocular Cytokine Profile and Therapeutic Response in Persistent Neovascular Age-Related Macular Degeneration

Citation: Rezar-Dreindl S, Sacu S, Eibenberger K, et al. The intraocular cytokine profile and therapeutic response in persistent neovascular agerelated macular degeneration. Invest Ophthalmol Vis Sci. 2016;57:4144-4150. DOI:10.1167/iovs.16-19772 PURPOSE. To investigate the course of inflammatory and angiogenic cytokines in the aqueous humor of patients with persistent/recurrent neovascular age-related macular degeneration (nAMD) under ranibizumab monotherapy (IVM) or ranibizumab plus dexamethasone combination treatment. METHODS. In this 12-month prospective study, 40 eyes with nAMD were treated with either IVM or combined treatment with ranibizumab plus intravitreal dexamethasone implant (IVC). Patients in the IVM group were treated following an &apos;&apos;as needed&apos;&apos; treatment regimen; patients in the IVC group received ranibizumab and a dexamethasone implant at baseline and were retreated with ranibizumab. At baseline and at each time of retreatment aqueous humor samples were taken. RESULTS. Before treatment, levels of macrophage chemoattractant protein (MCP)-1, monokine induced by c interferon (MIG), and lipocalin-2/ neutrophil gelatinase-associated lipocalin (NGAL) were elevated in nAMD patients compared to healthy controls (P ¼ 0.024; P ¼ 0.04; P ¼ 0.01). In contrast, tumor necrosis factor a, IL-12p70, and secreted protein acidic and rich in cysteine (SPARC) concentrations were lower (P ¼ 0.001; P ¼ 0.008; P ¼ 0.03), while vascular endothelial growth factor (VEGF) was not altered (45 6 6/51 6 12 pg/mL nAMD/ control group; P ¼ 0.6). During IVC, levels of VEGF, MIG, platelet-derived growth factor (PDGF)-AA, and transforming growth factor b1 (P ¼ 0.005; P ¼ 0.011; P ¼ 0.008; P ¼ 0.013) were reduced. Ranibizumab monotherapy did not influence the course of any inflammatory/ angiogenic cytokine. Interleukin 6 and PDGF-AA levels correlated with central retinal thickness changes (P ¼ 0.007; P ¼ 0.022). Over the 12-month period visual function was maintained with no significant differences during or between both treatment groups. CONCLUSIONS. Inflammatory proteins are involved in the pathogenesis of chronic macular edema due to AMD and are associated with disease activity. During combined treatment, levels of inflammatory and angiogenic cytokines decreased over a 12-month period with no superiority in functional outcome