Quinol-containing ligands enable high superoxide dismutase activity by modulating coordination number,charge, oxidation states and stability of manganese complexes throughout redox cycling

Reactivity assays previously suggested that two quinol-containing MRI contrast agent sensors for H₂O₂, [Mn(H2qp1)(MeCN)]²⁺ and [Mn(H4qp2)Br₂], could also catalytically degrade superoxide. Subsequently, [Zn(H2qp1)(OTf)]⁺ was found to use the redox activity of the H2qp1 ligand to catalyze the conversion of O₂˙⁻ to O₂ and H₂O₂, raising the possibility that the organic ligand, rather than the metal, could serve as the redox partner for O₂˙⁻ in the manganese chemistry. Here, we use stopped-flow kinetics and cryospray-ionization mass spectrometry (CSI-MS) analysis of the direct reactions between the manganese-containing contrast agents and O₂˙⁻ to confirm the activity and elucidate the catalytic mechanism. The obtained data are consistent with the operation of multiple parallel catalytic cycles, with both the quinol groups and manganese cycling through different oxidation states during the reactions with superoxide. The choice of ligand impacts the overall charges of the intermediates and allows us to visualize complementary sets of intermediates within the catalytic cycles using CSI-MS. With the diquinolic H4qp2, we detect Mn(iii)-superoxo intermediates with both reduced and oxidized forms of the ligand, a Mn(iii)-hydroperoxo compound, and what is formally a Mn(iv)-oxo species with the monoquinolate/mono-para-quinone form of H4qp2. With the monoquinolic H2qp1, we observe a Mn(ii)-superoxo ↔ Mn(iii)-peroxo intermediate with the oxidized para-quinone form of the ligand. The observation of these species suggests inner-sphere mechanisms for O₂˙⁻ oxidation and reduction that include both the ligand and manganese as redox partners. The higher positive charges of the complexes with the reduced and oxidized forms of H2qp1 compared to those with related forms of H4qp2 result in higher catalytic activity (k_cat ∼ 10⁸ M⁻¹ s⁻¹ at pH 7.4) that rivals those of the most active superoxide dismutase (SOD) mimics. The manganese complex with H2qp1 is markedly more stable in water than other highly active non-porphyrin-based and even some Mn(ii) porphyrin-based SOD mimics.

Manganese complexes with polydentate quinol-containing ligands are found to catalyze the degradation of superoxide through inner-sphere mechanisms. The redox activity of the ligand stabilizes higher-valent manganese species.     

Optimising time-varying gradient orientation for microstructure sensitivity in diffusion-weighted MR

Here we investigate whether varying the diffusion-gradient orientation during a general waveform single pulsed-field gradient sequence improves sensitivity to the size of coherently oriented pores over having a fixed orientation. The experiment optimises the shape and the orientation of the gradient waveform in each of a set of measurements to minimise the expected variance of estimates of the parameters of a simple model. A key application motivating the work is measuring the size of axons in white matter. Thus, we use a two compartment white matter model with impermeable, single-radius cylinders, and search for waveforms that maximise the sensitivity to axon radius, intra-cellular volume fraction and diffusion constants. Output of the optimisation suggests the only benefit of allowing the gradient orientation to vary in the plane perpendicular to the cylinders is that we can gain perpendicular gradient strength by maximising two orthogonal gradients simultaneously. This suggests that varying orientation in itself does not increase the sensitivity to model parameters. On the other hand, the variation in a plane containing the parallel direction increases the sensitivity significantly because parallel sensitivity improves the diffusion constant estimates. However, we also find that similar improvement in the estimates can be achieved without optimising the orientation, but by having one measurement in the parallel and the rest in the perpendicular direction. The optimisation searches a very large space where it cannot hope to find the global minimum so we cannot make a categorical conclusion. However, given the consistency of the results in multiple reruns and variations of the experiments reported here, we can suggest that for probing coherently oriented systems, pulse sequences with variable orientation, such as double-wave vector sequences, do not offer more advantage than fixed orientation sequences with optimised shape. The advantage of varying orientation is however likely to emerge for more complex systems with dispersed pore orientation.     

Second harmonic generation in thin Ge<Subscript>35</Subscript>Sb<Subscript>5</Subscript>S<Subscript>60</Subscript> films

Generation of the second optical harmonic is investigated in 250 to 1500-nm thick films of Ge₃₅Sb₅S₆₀ chalcogenide glass. It is shown that a decrease in quadratic optical susceptibility in thicker films can result from a decrease in the bulk contribution from the electric dipole to the susceptibility and can be used in nonlinear optical diagnostics of the films.     

Preparation of planar‐chiral multidonor phosphanylferrocene carboxamides and their application as ligands for palladium‐catalysed asymmetric allylic alkylation

Amide coupling of (S_p)‐2‐(diphenylphosphanyl)ferrocene‐1‐carboxylic acid with appropriate terminal amines mediated by 1‐hydroxybenzotriazole and a carbodiimide affords multi‐donor amides terminally functionalized with planar‐chiral (S_p)‐2‐(diphenylphosphanyl)ferrocen‐1‐yl moieties in good to excellent yields. Palladium catalysts based on these ligands efficiently promote asymmetric allylic alkylation of 1,3‐diphenylallyl acetate with in situ generated dimethyl malonate anion to give the C‐alkylated product with ees up to 93% at room temperature. Copyright © 2010 John Wiley & Sons, Ltd.     

Studies of the forced hydrolysis degradation of copper complexes with different oligosaccharides

Bioactive copper complexes with oligosaccharides, pullulan or dextran, are the objective of the present study, because of their possible biomedical applications. The alkaline and acid hydrolysis of the Cu(II) complexes with reduced low-molar pullulan or dextran were carried out by conductometric method. The influence of ligand constitutions on the stability of the complexes was examined on the basis of ligand property. The complexes degradation during alkaline and acid hydrolysis were carried out in sodium hydroxide and hydrochloric acid solutions of 0.1, 0.5, and 1.0 mol dm⁻³, at different temperature (25, 40, and 60°C, respectively). According to the obtained results by the conductivity investigation during forced degradation studies, it could be concluded that the Cu(II) complexes show the small pharmaceutical stability to both hydrolysis.     

Existence and physical uniqueness of the restricted evolution problem of the Einstein relativistic mechanics

The existence and physical uniqueness is proved for the restricted evolution problem in general relativity. Precisely, the Einstein equations for the gravitational field are analyzed in harmonic and generic adapted coordinates in order to prove the existence and uniqueness of solution in both systems of coordinates.     

Biodegradation of tobacco waste by composting: Genetic identification of nicotine-degrading bacteria and kinetic analysis of transformations in leachate

The tobacco industry produces large quantities of solid and liquid waste. This waste poses a significant environmental problem, as some major components are harmful and toxic. The aim of this work is to isolate and identify the nicotine-degrading microorganisms in the composting of tobacco waste. The bioremediation process for the detoxification of waste was carried out in a column reactor at an airflow-rate of 0.4 L min^?1 kg^?1. The concentrations of nicotine and number of CFU in the samples taken from reactor were monitored over nineteen days. After nineteen days, 89.8 % of nicotine conversion was obtained. A nicotine-degrading bacterium, strain FN, was isolated from the composting mass and identified as Pseudomonas aeruginosa on the basis of morphology, 16S rDNA sequence, and the phylogenetic characteristics. To confirm that the isolated Pseudomonas aeruginosa FN is the actual nicotine degrader, batch experiments were performed using tobacco leachate. It was confirmed that the strain FN possesses a considerable capacity to degrade nicotine with simultaneous COD removal. The Monod kinetic model for single substrate was applied to obtain the substrate degradation rate and half saturation constant.