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.     

Time dependence of charge transfer processes in diamond studied with positrons

We have developed a method called optical transient positron spectroscopy and apply it to study the optically induced carrier trapping and charge transfer processes in natural brown type IIa diamond. By measuring the positron lifetime with continuous and pulsed illumination, we present an estimate of the optical absorption cross section of the vacancy clusters causing the brown color. The vacancy clusters accept electrons from the valence band in the absorption process, giving rise to photoconductivity.     

Resolving Extensions of Finitely Presented Systems

In this paper we extend certain central results of zero dimensional systems to higher dimensions. The first main result shows that if (Y,f) is a finitely presented system, then there exists a Smale space (X,F) and a u-resolving factor map π ₊:X→Y. If the finitely presented system is transitive, then we show there is a canonical minimal u-resolving Smale space extension. Additionally, we show that any finite-to-one factor map between transitive finitely presented systems lifts through u-resolving maps to an s-resolving map.     

Hyperplane Envelopes and the Clairaut Equation

The subject of envelopes has been part of differential geometry from the beginning. This paper brings a modern perspective to the classical problem of envelopes of families of affine hyperplanes. In the process, the classical results are generalized and unified.     

The H(2)(18)O solvent-induced isotope shift in (19)F NMR

The H(2)(16)O/H(2)(18)O solvent-induced isotope shifts ((18)O SIIS) of the (19)F NMR signals of a number of fluorine compounds have been measured. These isotope shifts are observed to be upfield, downfield, or zero, depending on the specific compound and the precise solution conditions. At 25 degrees C and with an (18)O enrichment of 86%, the (18)O SIIS of several fluorinated amino acids were in the range of 0.0014-0.0018 ppm downfield. 5-Fluorouridine displays a significantly wider range of (18)O SIIS values. A 5-fluorouridine-labeled 16-mer RNA also displayed observable (18)O SIIS values, but the characteristics of these were significantly modified from those of free 5-fluorouridine. The experimental observations are consistent with the (18)O SIIS being composed of upfield and downfield components, with the relative contributions of these determining the size and direction of the overall isotope shift. This is discussed in terms of a combination of van der Waals interactions between the fluorine atom and the solvent, electrical and hydrogen bonding effects, and the perturbations to these due to (18)O substitution in the solvent water. This isotope effect promises to be a highly useful tool in a range of (19)F NMR studies.     

Interactive optimization

Optimization algorithms or heuristics in which the user interacts significantly either during the solution process or as part of post-optimality analysis are becoming increasingly popular. An important underlying premise of such man/machine systems is that there are some steps in solving a problem in which the computer has an advantage and other steps in which a human has an advantage. This paper first discusses how man/machine systems can be useful in facilitating model specification and revision, coping with aspects of a problem that are difficult to quantify and assisting in the solution process. We then survey successful systems that have been developed in the areas of vehicle scheduling, location problems, job shop scheduling, course scheduling, and planning language-based optimization.     

Further studies on the application of vinylogous amides and β-halovinylaldehydes to the regiospecific synthesis of unsymmetrical,polyfunctionalized 2,3,4- and 1,2,3,4- substituted pyrroles

Highly functionalized pyrroles with appropriate regiochemical functionality represent an important class of marine natural products and potential drug candidates. We describe herein a detailed study of the reaction of α-aminoacid esters with vinylogous amides and also β-halovinylaldehydes for the regiospecific synthesis of 2,3,4-trisubstituted and 1,2,3,4-tetrasubstituted pyrroles. Since the vinylogous amides and β-halovinylaldehydes are readily available precursors, rapid access to a wide variety of unsymmetrically substituted pyrroles is accomplished via this methodology.     

Coaxial configuration of the dielectric Cherenkov maser

The linearized Lorentz force, continuity equation, and Maxwell's equations are used to calculate the system dispersion relation for a coaxial configuration of the dielectric Cherenkov maser. The system consists of two coaxial conductors lined with dielectric and an annular relativistic electron beam, which propagates between the two liners. The dispersion relation for the beam and dielectric-lined coaxial waveguide structure and the no-beam system that describes the dependence of the generated frequency on the coaxial waveguide parameters are presented. Using the linearized dispersion relation, the growth rate for the beam-TM_0n waveguide mode instability is calculated in the strong-coupling tenuous beam limit     

Asymptotic behavior of the correlation functions for a Brownian oscillator with viscous aftereffects

Correlation functions are derived in explicit form for the asymptotic behavior at for a Brownian oscillator with viscous aftereffects.Translated from Izvestiya Vysshikh Uchebnykh Zavedenii, Fizika, No. 4, pp. 22–25, April, 1973.I am indebted to D. I. Polishchuk and I. Z. Fisher for discussions.     

Active cancellation of occlusion: an electronic vent for hearing aids and hearing protectors

The occlusion effect is commonly described as an unnatural and mostly annoying quality of the voice of a person wearing hearing aids or hearing protectors. As a result, it is often reported by hearing aid users as a deterrent to wearing hearing aids. This paper presents an investigation into active occlusion cancellation. Measured transducer responses combined with models of an active feedback scheme are first examined in order to predict the effectiveness of occlusion reduction. The simulations predict 18 dB of occlusion reduction in completely blocked ear canals. Simulations incorporating a 1 mm vent (providing passive occlusion reduction) predict a combined active and passive occlusion reduction of 20 dB. A prototype occlusion canceling system was constructed. Averaged across 12 listeners with normal hearing, it provided 15 dB of occlusion reduction. Ten of the subjects reported a more natural own voice quality and an appreciable increase in comfort with the cancellation active, and 11 out of the 12 preferred the active system over the passive system.