Occurrence, behavior and effects of nanoparticles in the environment.

Ozonation of drinking water: part I. Oxidation kinetics and product formation.

Radical-mediated damage to proteins may be initiated by electron leakage, metal-ion-dependent reactions and autoxidation of lipids and sugars. The consequent protein oxidation is O2-dependent, and involves several propagating radicals, notably alkoxyl radicals. Its products include several categories of reactive species, and a range of stable products whose chemistry is currently being elucidated. Among the reactive products, protein hydroperoxides can generate further radical fluxes on reaction with transition-metal ions; protein-bound reductants (notably dopa) can reduce transition-metal ions and thereby facilitate their reaction with hydroperoxides; and aldehydes may participate in Schiff-base formation and other reactions. Cells can detoxify some of the reactive species, e.g. by reducing protein hydroperoxides to unreactive hydroxides. Oxidized proteins are often functionally inactive and their unfolding is associated with enhanced susceptibility to proteinases. Thus cells can generally remove oxidized proteins by proteolysis. However, certain oxidized proteins are poorly handled by cells, and together with possible alterations in the rate of production of oxidized proteins, this may contribute to the observed accumulation and damaging actions of oxidized proteins during aging and in pathologies such as diabetes, atherosclerosis and neurodegenerative diseases. Protein oxidation may also sometimes play controlling roles in cellular remodelling and cell growth. Proteins are also key targets in defensive cytolysis and in inflammatory self-damage. The possibility of selective protection against protein oxidation (antioxidation) is raised.

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Biochemistry and pathology of radical-mediated protein oxidation

The generation of reactive oxygen species may be both beneficial to cells, performing a function in inter- and intracellular signalling, and detrimental, modifying cellular biomolecules, accumulation of which has been associated with numerous diseases. Of the molecules subject to oxidative modification, DNA has received the greatest attention, with biomarkers of exposure and effect closest to validation. Despite nearly a quarter of a century of study, and a large number of base- and sugar-derived DNA lesions having been identified, the majority of studies have focussed upon the guanine modification, 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-OH-dG). For the most part, the biological significance of other lesions has not, as yet, been investigated. In contrast, the description and characterisation of enzyme systems responsible for repairing oxidative DNA base damage is growing rapidly, being the subject of intense study. However, there remain notable gaps in our knowledge of which repair proteins remove which lesions, plus, as more lesions identified, new processes/substrates need to be determined. There are many reports describing elevated levels of oxidatively modified DNA lesions, in various biological matrices, in a plethora of diseases; however, for the majority of these the association could merely be coincidental, and more detailed studies are required. Nevertheless, even based simply upon reports of studies investigating the potential role of 8-OH-dG in disease, the weight of evidence strongly suggests a link between such damage and the pathogenesis of disease. However, exact roles remain to be elucidated.

Oxidative DNA damage and disease: induction, repair and significance

Protein Radicals in Enzyme Catalysis.

A wonderfully successful NATO Advanced Study Institute on "Sulfur-Centered Reactive Intermediates in Chemistry and Biology" was held 18-30 June, 1989, at the Hotel Villa del Mare in Maratea, Italy. Despite the beautiful setting with mountains behind us and over looking the clear blue Mediterranean Sea under a cloudless sky (and with a private beach available), the lectures were extremely well attended. While some credit can go to the seriousness of the students, more must go to the calibre of speakers and the high quality of C. Chatgilialoglu, and Co-Director, Professor K. -D. their presentations. The Director, Dr. Asmus, are to be congratulated for putting together such an outstanding scientific program. Dr. Chatgilialoglu is also to be commended for arranging an equally stimulating social pro gram which included bus, train and boat trips to many local sites of interest. It was particularly fitting that a meeting on the chemistry and biochemistry of sulfur should be held in Italy since Italian chemists have made major contributions to our under standing of the organic chemistry of sulfur, including the chemistry of its reactive inter mediates. The early Italian interest in sulfur chemistry arose from the fact that Italy, or more specifically, Sicily, was a major world producer of sulfur prior to the development and exploitation of the Frasch process in Texas and Louisiana."

Sulfur-centered reactive intermediates in chemistry and biology

The reaction mechanism of the OH. radical induced oxidation of methionine in aqueous solutions has been investigated by radiation chemical methods, mainly ns-ms pulse radiolysis. The initial step is a competitive process between addition of the OH. radical to the sulfur atom and hydrogen abstraction at a 4:1 ratio in favor of the former. In strong acid solutions (pH approx. less than or equal to 3) the subsequent mechanism is practically identical with the oxidation mechanism of aliphatic thioethers. The intermediate of most interest in this case is a sulfur-centered radical cation complex with an absorption maximum at 480 nm. At higher pH in slightly acid, neutral, and basic solutions the mechanism is more complex, essentially involving a fast (k > 4 x 10/sup 6/ s/sup -1/) intramolecular and probably sterically assisted oxidation of the amino group by the primarily oxidized sulfur function. This process includes irreversible decarboxylation of the amino acid. Both the CO/sub 2/ and the remaining ..cap alpha..-amino radicals have been identified and their yields determined. The N-oxidation depends on the reduction potential of the amino group and takes place with both the basic and the zwitterionic form of methionine - in the latter case on accountmore » of the rapid proton exchange between the NH/sub 3//sup +/ and COO/sup -/ groups. Complete protonation of the carboxyl group in very acid solutions, or by the addition of powerful proton donors, e.g., H/sub 2/PO/sub 4//sup -/, or the introduction of an electron-withdrawing substituent such as in N-acetylmethionine lowers the reduction potential to such an extent that the oxidation site may effectively remain at the sulfur. A detailed mechanism with the associated reaction kinetics and some physicochemical properties of the intermediates are presented and discussed.« less

Mechanism of the hydroxyl radical induced oxidation of methionine in aqueous solution

Time-resolved and steady-state techniques have been performed to investigate the photophysical properties of C60[C(COOEt)2] (Ia), e-C60[COOEt)2]2 (IIa) (e = equatorial), trans-3-C60[C(COOEt)2]2 (IIb), trans-2-C60[C(COOEt)2]2 (IIc), and e,e,e-C60[C(COOEt)2]3 (III) (e = equatorial). Picosecond-resolved energy transfer to the fullerene core results in the rapid formation of the excited singlet state with remarkably blue-shifted singlet−singlet (S*1 → S*n) transitions (868 nm (III)) relative to pristine C60 (920 nm). Intersystem crossing to the energetically lower lying excited triplet state exhibits a deceleration with increasing number of functionalizing addends. The corresponding triplet−triplet (T*1 → T*n) absorption energies also show a significant dependence on the degree and site of functionalization, spreading over a range of 100 nm (750 nm for 3C60 to 650 nm for e,e,e-(3C60)[C(COOEt)2]3 (III)). Energy transfer from radiolytically excited biphenyl (3BP) to the fullerene's ground state corroborates the...

Photophysical Properties of Mono- and Multiply-Functionalized Fullerene Derivatives

Electron Transfer from C76 (C2v‘) and C78 (D2) to Radical Cations of Various Arenes: Evidence for the Marcus Inverted Region

Radiation chemical methods were used to investigate the reactions of glycine anions, H2NCH2CO2- (Gly-), with •OH, (CH3)2C•OH, and •CH3 radicals. A major and most significant product from all of these processes is CO2. Pulse-radiolysis revealed that the initial step in the •OH-induced mechanism is oxidation of the amino group, producing +H2N•-CH2-CO2- and HN•-CH2-CO2- with yields of 63% and 37%, respectively. The amino radical cation, +H2N•-CH2-CO2-, suffers fast (≤100 ns) fragmentation into CO2 + •CH2NH2. The other primary radical, HN•-CH2-CO2-, can also be converted into the decarboxylating +H2N•-CH2-CO2- by reaction with proton donors such as phosphate (H2PO4-/k = 7.4 × 107 M-1 s-1, and HPO42-/k = 2.5 × 105 M-1 s-1) or the glycine zwitterion, Gly± (k = 3.9 × 105 M-1 s-1), but only on a much longer (typically μs to ms) time scale (k ≈ 4 × 105 M-1 s-1). Competitively, the HN•-CH2-CO2- transforms into a carbon-centered radical H2N-C•H-CO2- either by an intramolecular 1,2-H-atom shift (k = (1.2 ± 1.0) × 103...

Klaus-Dieter Asmus

Papers

Sulfur-centered reactive intermediates in chemistry and biology

Mechanism of the hydroxyl radical induced oxidation of methionine in aqueous solution

Photophysical Properties of Mono- and Multiply-Functionalized Fullerene Derivatives

Electron Transfer from C76 (C2v‘) and C78 (D2) to Radical Cations of Various Arenes: Evidence for the Marcus Inverted Region

Glycine Decarboxylation: The Free Radical Mechanism