Hypothesis:soluble Aβ oligomers in association with redox-active metal ions are the optimal generators of reactive oxygen species in Alzheimer's disease

Considerable evidence points to oxidative stress in the brain as an important event in the early stages of Alzheimer's disease (AD). The transition metal ions of Cu, Fe, and Zn are all enriched in the amyloid cores of senile plaques in AD. Those of Cu and Fe are redox active and bind to Aβ in vitro. When bound, they can facilitate the reduction of oxygen to hydrogen peroxide, and of the latter to the hydroxyl radical. This radical is very aggressive and can cause considerable oxidative damage. Recent research favours the involvement of small, soluble oligomers as the aggregating species responsible for Aβ neurotoxicity. We propose that the generation of reactive oxygen species (i.e., hydrogen peroxide and hydroxyl radicals) by these oligomers, in association with redox-active metal ions, is a key molecular mechanism underlying the pathogenesis of AD and some other neurodegenerative disorders

Stable radicals observed in the flesh of irradiated citrus fruits by electron spin resonance spectroscopy for the first time.

The ESR spectra of the flesh of a selection of unirradiated and γ-irradiated citrus fruits have been obtained. When dried, the flesh from unirradiated fruits gives rise to virtually no ESR spectrum. However, the flesh of irradiated fruits exhibit a strong spectrum with radiation induced features which show a high degree of reproducibility within the fruits examined. These features have been previously observed in spectra from the intact skin and skin components of irradiated citrus fruits. It is believed that this is the first time that radicals have been observed by ESR in the flesh of irradiated fruits

The interaction between radicals derived from two di-t-alkyl peroxides with some monomers and polymers.

The thermolysis of di-tert-butyl and di-t-amyl peroxides in n-decane and with poly(methyl methacrylate) and poly(ethylene glycol) in chlorobenzene has been studied in the presence of tri-tert-butylnitrosobenzene as a spin trap. The major reaction pathways of the resulting t-alkoxyl radicals were β-scission and hydrogen atom abstraction. Thermolysis of the same peroxides in the presence of methyl methacrylate and methyl acrylate led to the trapping of growing polymer chains alongside unreacted alkyl radicals (again formed via β-scission of the first generation t-alkoxyl radicals). In some of the spectra, hyperfine coupling to γ-protons was observed. The hydrogen abstracting ability of radicals present during thermolysis of both peroxides has been compared in the presence of MA

Radical concentrations and reaction temperature profiles during the (batch) core-shell emulsion polymerisation of methyl methacrylate and butyl acrylate, studied by electron spin resonance spectroscopy.

Electron spin resonance (ESR) spectroscopy has been employed, together with the cryogenic quenching technique, to monitor occluded radical concentrations during methyl methacrylate-butyl acrylate core-shell polymerizations. Occluded radicals are only detected during the preparation of poly(methyl methacrylate) cores (seeds) presumably because a higher mobility of unterminated chains in poly(butyl acrylate) seeds reduces steady state concentrations. Addition of either butyl acrylate or methyl methacrylate as a second charge of (shell) monomer to a poly(methyl methacrylate) seed results in an immediate decrease in the occluded radical concentration to below that of the detection limit of the electron spin resonance spectrometer. This is due to an increase in chain mobility within polymer particles as a result of their reswelling in the presence of (fresh) unreacted monomer. A return of occluded radical activity is only observed when the second charge of monomer is methyl methacrylate. In systems where occluded radicals are detected, they reach a maximum concentration shortly after the reaction temperature maximum and, thereafter, they decay via a second order mutual termination process

Reaction temperature profiles and radical concentration measurements on batch emulsion copolymerizations of methyl-methacrylate and butyl acrylate.

Electron spin resonance (ESR) spectroscopy has been employed to monitor the occluded radical concentration during the batch (unseeded) emulsion copolymerization of methyl methacrylate and butyl acrylate. Occluded radical concentrations, above the detection limit of the ESR spectrometer, are only observed at methyl methacrylate mole fractions >0.96. The occluded radicals reach a maximum concentration at high conversion (ca 95%) and thereafter their concentraion declines via a second order termination process. The variation in the maximum reaction temperature and the time at which this maximum occurs with mole fraction has also been monitored and is discussed. The most surprising feature of these latter observations is that the rate of polymerization is much faster for butyl acrylate than for methyl methacrylate despite the greater propagation rate constant of the latter

An ESR spin-trap study of radicals present during the thermolysis of some di-t-alkyl peroxides.

The thermolysis mechanism of di-tert-butyl and di-tert-amyl peroxide was investigated in a variety of solvents employing electron spin resonance in collaboration with the spin-trapping technique. The tert-amyloxyl radical was trapped for the first time during the thermolysis of di-tert-amyl peroxide. The relative ease of -scission of the tert-amyloxyl radical to give propan-2-one and butan-2-one was established as 32:1 at 382 K. In addition, competition reactions indicate that radicals derived from di-tert-butyl peroxide are ca. 5.5 times more reactive than those derived from di-tert-amyl peroxide towards hydrogen atom abstraction from toluene at 382 K

Application of frequency domain deconvolution to DQF-COSY spectra for the determination of coupling constants as a tool for signal assignment based on coupling networks

Scalar coupling constants can be extracted from the cross peaks of correlation spectra by applying deconvolution to the frequency domain. This requires high resolution in the directly detected dimension. A three-step automated procedure is presented as a free package running in combination with a major commercial processing software. The initial step allows one to measure coupling constants in an interactive manner in high-resolution cross-peak multiplets of weakly coupled spin systems. The user can follow the recursive analysis to assess the reliability of the results. If needed, the course of the automatic procedure can be changed. A second module compiles the data of the cross-peak analysis and assembles the proton spin network. The algorithm assigns data to a given nucleus if it encounters full consistency of both chemical shifts and coupling constants in all relevant cross peaks. The pairing of signals symmetric with respect to the diagonal defines the connectivity of the spin network. The last module displays the coupling network in a pleasing presentation. Application to androst-4-ene-3, 17-dione is presented. This example shows that assignment of the coupling network to the molecular structure becomes straightforward

ESR dating of quartz phenocrysts in some rhyolitic extrusive rocks using A1 and Ti impurity centres.

ESR has been employed to determine the eruption date of rhyolitic rocks from three different tectonic settings. Samples from the Olkaria complex, Kenya rift valley, yielded ages of 31±3 and 38±5 ka (148a) and 23±4 and 34±8 ka (570) from the Al and Ti centres, respectively. These compare with an inferred formation age of 65±12 ka (148a), obtained from U-series isochrons, and an eruption age of 5.7–9.7 ka (570), based on 14C and lake stands. Glass (melt) inclusions in sample 570 may have distorted the ESR age. The Youngest Toba Tuff (YTT), Sumatra, gave an average ESR eruption age of 81±17 ka which compares well with K/Ar and 40Ar/39Ar ages in the range 73–75 ka. However, there is evidence of thermal annealing in the Oldest (OTT) and Middle (MTT) Toba Tuffs by the more recent YTT eruption, with mean ages of ca. 349 ka and 326 ka, respectively, significantly below the K/Ar age of 840±30 ka (OTT) and the 40Ar/39Ar age of 501±5 ka (MTT). A sample from the Battleship Rock Tuff, Jemez Volcanic Field, New Mexico, gave a mean ESR age of ca. 247 ka which contrasts markedly with a previously determined ESR age of 59±6 ka, but compares more favourably with previous K/Ar ages of 278±52, 130±70 and 180±70 ka. Subsequent geothermal activity and high ambient temperatures in this area may be responsible for these apparent discrepancies