Robin L. Willson

Radical-cations as reference chromogens in kinetic studies of ono-electron transfer reactions: pulse radiolysis studies of 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate)

Electrophilic free radicals such as OH˙, RS˙, CCl3O2˙, Br2˙–, and (SCN)2·– react rapidly with 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate)(ABTS) to form the radical-cation ABTS˙+, λmax. 415 nm (Iµ 3.6 × 104 l mol–1 cm–1). Absolute rate constants for these electron-transfer reactions have been determined by pulse radiolysis. Results suggest that ABTS˙+ is likely to prove a useful reference free radical, not only for the study of reactions in which a free radical is the electron acceptor, but also in studies of reactions of organic radicals with sulphydryl compounds.

Reactions of the carbon tetrachloride-related peroxy free radical (CCl3O2.) with amino acids : Pulse radiolysis evidence

Abstract Pulse radiolysis studies indicate that the free radical CCl3O2. but not the radical CCl3 reacts rapidly with tryptophan, tyrosine, phenol or promethazine to yield transient products with strong visible absorption spectra.

Pulse radiolysis studies on the oxidation of organic radicals in aqueous solution

Pulse radiolysis has been used to measure directly the absolute rates of oxidation by ferricyanide ion of various radicals produced by OH attack on organic solutes. These include mono, di- and polyhydroxylic compounds, hydroxy acids, polyethylene oxides of molecular weight 200, 6000 and 20 000 and the amino acid serine. Radicals produced by hydrogen abstraction from α carbon atoms in alcohols are oxidized at, or near, diffusion-controlled rates, whereas the reactions are much slower for radicals formed by OH-attack elsewhere. The technique has been used to measure the percentage OH-attack at the α position for a series of straight and branched-chain alcohols. Oxygen competes with ferricyanide for radical oxidation. The data for oxygen-containing solutions fit a simple radical-competition scheme which has been used to measure rates of peroxy-radical formation. These approach diffusion-controlled limits.

Free radicals and singlet oxygen scavengers: Reaction of a peroxy-radical with β-carotene, diphenyl furan and 1,4-diazobicyclo(2,2,2)-octane

The ‘singlet oxygen scavengers’. 1,4-diazobicyclo(2,2,2)-octane (DABCO), diphenyl furan and β-carotene react rapidly with the organic peroxyradical CCl3O2•. The absolute reaction rate constants k = 1.2 ± 0.2 × 107, 6 ± 2 × 107 at 1.5 ± 0.2 × 109 M−1s−1 respectively have been determined by pulse radiolysis. Comparison with other data suggest that other free radicals are also likely to react with these compounds; in the case of the hydroxyl radical and DABCO k = 1.25 × 109 M−1s−1 has been determined.

Glutathione Peroxidase: Effect of Superoxide, Hydroxyl and Bromine Free Radicals on Enzyme Activity

(1980). Glutathione Peroxidase: Effect of Superoxide, Hydroxyl and Bromine Free Radicals on Enzyme Activity. International Journal of Radiation Biology and Related Studies in Physics, Chemistry and Medicine: Vol. 37, No. 2, pp. 213-217.

The Reaction of Oxygen with Radiation-induced Free Radicals in DNA and Related Compounds

SummaryThe transient absorption spectra produced on pulse radiolysis of aqueous solutions of DNA and related biochemicals, saturated with mixtures of nitrous oxide and oxygen, have been measured. Spectra observed immediately after the radiation pulse have been assigned to the respective adducts formed by the reaction of hydroxyl radicals. Except in the cases of 5-bromouracil, guanylic acid and DNA, the absorptions decayed rapidly and first order in oxygen. Absolute rate constants for the reaction of oxygen with the adducts of several pyrimidine bases have been determined and approach those of diffusion-controlled reactions. Analogous rates of reaction for the related nucleotides and nucleosides are approximately 50 per cent slower. Absolute rate constants for the reaction of oxygen with the hydroxy-adducts of tryptophan and histidine have also been determined.

Metronidazole (“Flagyl”). A radiosensitizer of hypoxic cells

Abstract The radiosensitizing properties of metronidazole have been studied using bacteria, bean roots, and mammalian cells in vitro as test systems. Metronidazole has been shown to sensitize only anoxic cells in a concentration-dependent manner, a maximum enhancement ratio of 1·9 being obtained at 8 mmol/1. metronidazole concentration for mammalian cells. The effect of added SH compounds on the sensitizing effect of metronidazole was studied in bacteria and bean roots. Metronidazole sensitized bacteria to the effects of neutron irradiation by a factor of only 1·4. The mechanism of sensitization by metronidazole is discussed in the light of pulse radiolysis and ESR data, and its action compared with that of oxygen. Pharmacological data presented suggest that in vivo testing of metronidazole should be possible and that any radiosensitizing effects shown may be related to measured serum concentrations.

Electron Affinic Sensitization: Part II: Para-Nitroacetophenone: A Radiosensitizer for Anoxic Bacterial and Mammalian Cells

SummaryThe radiosensitizing properties of the highly electron-affinic nitroketone, para-nitroacetophenone (PNAP) have been investigated in resistant and sensitive bacteria, fern spores, mammalian cells in tissue culture and in suspensions of bacteriophage. Radiosensitization occurs in anoxic suspensions of Serratia marcescens Micrococcus radiodurans and in anoxic preparations of Chinese hamster cells line V79–379A. The sensitization of the mammalian cells (enhancement ratio 1·7 for 0·4 mM PNAP) is not inhibited in the presence of serum protein. No sensitization was observed for the spore of the fern Osmunda regalis.PNAP resembles oxygen in conferring some radioprotection on suspensions of bacteriophage T7 irradiated in broth.

Thiyl free radicals: direct observations of electron transfer reactions with phenothiazines and ascorbate

Absolute rate constants for the reaction of the thiyl radicals derived from cysteamine, cysteine, glutathione, penicillamine, and 2-mercaptopropionylglycine (Thiola) with the phenothiazines, promethazine and chlorpromazine and with ascorbate ion, have been measured by pulse radiolysis and have been found to lie in the range 0.03–1.3 × 109 I mol–1 s–1. The reactions are considered to occur by an electron transfer mechanism. The possibility that, in biochemical systems, glutathione can act as a catalyst linking hydrogen atom and electron transfer reactions is suggested.

Metronidazole (‘Flagyl’): Mechanisms of Radiosensitization

SummaryRadiation biochemical and bacterial studies have been undertaken to investigate possible mechanisms of radiosensitization by metronidazole. It is concluded that the nitro-group plays a major role in its action and that at least four mechanisms may be operative under hypoxic conditions.(i) enzyme-catalysed depletion of nucleophiles,(ii) fixation of organic radicals,(iii) interference with recombination reactions,(iv) formation of toxic products.