OH�� Radical Production Induces Direct Enhancement of the Amylo?d �� Protein/Chondroitin Sulfate Binding: Inhibition by Potentially Radical Scavengers, a Biochromatographic and Thermodynamic Model

??-Amyloid (A??) is a major component of the senile plaques characteristic of Alzheimer disease (AD). Chondroitin sulfate (CS) and glycoaminoglycan (GAG) are also localized throughout the senile plaques in AD. In previous studies, the interaction of the A?? protein with CS immobilized on a chromatographic support and the role of aluminum and copper cations was studied using a molecular chromatographic approach [1, 2]. Here, we demonstrated the direct implication of OH· radical formation on this binding via a novel analytical procedure. The binding of A?? amyloid on CS was accompanied by an OH· radical uptake. The A?¨CCS complex was stabilized by the OH· radical via the creation of about one to two hydrogen bonds. The addition in the medium of a radical scavenger allowed decreasing the A??/CS association and thus confirmed the positive role of these compounds in amyloidosis.     

Spatiotemporal and statistical symmetries

The notion of symmetries, either statistical or deterministic, can be useful for the characterization of complex systems and their bifurcations. In this paper, we investigate the connection between the (microscopic) spatiotemporal symmetries of a space-time functionu(x, t), on the one hand, and the (macroscopic) symmetries of statistical quantities such as the spatial (resp. temporal) two-point correlations and the spatial (resp. temporal) average, on the other hand. We show, how, under certain conditions, these symmetries are related to the symmetries of the orbits described byu(x, t) in the characteristic (phase) spaces. We also determine the largest group of spatiotemporal symmetries (in the sense introduced in our earlier work) satisfied by a given space-time functionu(x, t) and indicate how to extract the subgroups of point symmetries, namely those directly implemented on the space and time variables. Conversely, we determine all the functions invariant by a given space-time symmetry group. Finally, we illustrate all the previous points with specific examples.     

Diastereoselective spiroannulation of phenolic substrates: synthesis of (+/-)-2-tert-butyl-6-methoxy-1-oxaspiro[4,5]deca-6,9-diene-8-one

The synthesis of a new spiroether is described. The title compound is obtained as a diastereomeric mixture in 45% yield.     

New 64Cu PET imaging agents for personalised medicine and drug development using the hexa-aza cage, SarAr

The success of positron emission tomography (PET) in personalised medicine and drug development requires radioisotopes that provide high quality images and flexible chemistry for a broad application. 64Cu is arguably one of the most suitable PET isotopes for imaging with the evolving target agents, but there are not many appropriate chelating agents for 64Cu and this has limited its wider application. The bi-functional chelator, SarAr is known to bind 64Cu2+ quantitatively (i.e. one metal per ligand present) and rapidly (<2 min) at 10(-6) M over a range of pH (4-9). In this paper the conjugation of SarAr to the whole and fragmented antibody is described. Conjugation of the SarAr to the protein does not impair its coordination of the 64Cu. It complexes the 64Cu2+ rapidly, quantitatively and essentially irreversibly at pH 5. Animal studies show that the 64Cu-SarAr-immunoconjugates maintain their specificity for the target and are stable in vivo. Also, SarAr is a platform technology, is easy to use in a kit formulation and is readily adaptable for the wider application in 64Cu PET imaging.     

Extended tunnelling states in the benzoic acid crystal: infrared and Raman spectra of the OH and OD stretching modes

We compare Raman and infrared spectra of the nuOH/OD modes in benzoic acid crystal powders at 7 K. The extremely sharp Raman bands contrast to the broad infrared profiles and suggest adiabatic separation of hydrogen (deuterium) dynamics from the crystal lattice. There is no evidence of any proton-proton coupling term. The assignment scheme is consistent with a quasisymmetric double-minimum potential, largely temperature independent. Tunnel splitting is a major band shaping mechanism, in addition to anharmonic coupling with lattice modes. The proton/deuteron dynamics are rationalized with nonlocal pseudoparticles and extended states. We propose a symmetry-related damping mechanism to account for the broad infrared profiles, as opposed to the sharp Raman bands. We assign spectral features to distinct interconversion mechanisms based on either pseudoparticle transfer or adiabatic pairwise transfer. We establish close contacts with theoretical models based on first-principles calculations.     

Studies of the inner reorganization energies of the cation radicals of 1,4-bis(dimethylamino)benzene, 9,10-bis(dimethylamino)anthracene, and 3,6-bis(dimethylamino)durene by photoelectron spectroscopy and reinterpretation of the mechanism of the electrochemical oxidation of the parent diamines

The inner reorganization energy of the cation radical of 1,4-bis(dimethylamino)benzene, 1, has been determined to be 0.72 +/- 0.02 eV by means of gas-phase photoelectron spectroscopy (PES). PES studies of 9,10-bis(dimethylamino)anthracene, 2, and 3,6-bis(dimethylamino)durene, 3, demonstrate that their reorganization energies are smaller than that of 1. The effect of lowering the inner reorganization energy on the rate constant for an electrochemical electron-transfer reaction is to increase the electron-transfer rate constant, k(s). However, voltammetric studies of the two-electron oxidation of 2 and 3 indicate that the values of k(s) for each step are smaller than those for 1, in contradistinction to the measured differences in reorganization energies. The voltammetric studies of 2 and 3 were reinterpreted according to a mechanism in which each step of oxidation was written as a two-step process, electron transfer with a small inner reorganization energy plus a chemical step of structural change. The agreement of simulations according to this mechanism with the experimental data was excellent. The new reaction scheme eliminated some suspicious features previously obtained with an analysis where electron transfer and structural change were considered to be concerted. In particular, all electron-transfer coefficients (alpha) were close to one-half, whereas the earlier treatment produced values of alpha much larger or smaller than one-half.     

Optimization of plasmonic heating by gold nanospheres and nanoshells

Gold nanoparticles have strong and tunable absorption peaks in their optical extinction spectra, a phenomenon that has recently been exploited to generate localized heating in the vicinity of these particles. However the optimum particle geometry and illumination regime to maximize these effects appears not to have been previously examined in any detail. Here we show that the interplay between the particles' absorption cross-sections, volume, and surface area lead to there being specific conditions that can maximize particle temperature and surface heat flux. Optical absorption efficiencies were calculated from the formulation of Mie, and radiative, convective, and conductive heat transfer models were used to model the thermal performance of particles in different situations. Two technologically relevant scenarios for illumination, namely, irradiation by sunlight at 800 W/m2 and by a monochromatic laser source of 50 kW/m2 tuned to the peak absorption wavelength, were considered. For irradiation by sunlight, the resultant heat flux is optimized for an 80 nm diameter nanoshell with an aspect ratio of 0.8, while for irradiation by laser the maximum heat flux is found for 50 nm nanoshells, with an aspect ratio of 0.9.     

Synthesis and properties of a functionalized heterobimetallic Re(I)–Gd(III) complex as a potential dual-contrast agent for molecular imaging

In the design of dual-imaging probes, the first functionalized and neutral heterobimetallic Re(I)–Gd(III) complex, highly soluble in aqueous solutions, has been prepared. This system exhibits interesting photophysical properties (λ_em = 578 nm, ? = 1.4%) for optical imaging and substantial higher relaxivity (r₁ = 6.6 mM⁻¹ s⁻¹ at 0.47 T and 37 °C) than the clinically used MRI contrast agents. Moreover, this system incorporates an aromatic ester functionality suitable for bioconjugation.