Pulse radiolysis studies of WR-1065. 1984

J F Ward, and V O Mora-Arellano

WR-1065, the dephosphorylated sulfhydryl form of WR-2721 has been suggested as the metabolite responsible for the radioprotective abilities of the latter and as being active during the radiation chemical stage of damage production. Hence this study was performed to determine some of the radiation chemical parameters of the compound. Pulse radiolysis techniques, developed for use with SH compounds, were employed in the current work: Three systems were used to attempt to measure the rate constant for reaction of OH. radicals with WR-1065; (a) Competition with phenylalanine, in which the decrease in the amount of RSSR- caused by the addition of phenylalanine is monitored; this failed because of the absence of an absorbance attributable to RSSR-. (b) Competition with 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulfonate) (ABTS), monitoring the decrease in OH. induced ABTS absorbance caused by WR-1065 addition. This was unsuccessful due to reaction of RS. with ABTS. (c) Competition with CNS-, observing the decrease in (CNS)-2 caused by WR-1065 addition indicates that the second order rate constant for reaction of OH. with WR-1065 is 9.2 +/- 0.3 X 10(9) M-1 s-1. To investigate the ability of WR-1065 to react with DNA radicals the yield of ABTS radicals was monitored in a situation where DNA scavenges 50% of the OH. radicals in the presence of ABTS (20%) and WR-1065 (30%). DNA radicals were shown not to react with ABTS but WR-1065 radicals do, the absence of additional ABTS absorbing species indicates that DNA radicals do not react with WR-1065 under the experimental conditions used. An attempt was made to investigate the possibility that WR-1065 is concentrated close to DNA macromolecules in solution: The rate constant for reaction Br2- with WR-1065 was measured in the presence and in the absence of excess DNA (with which Br2- was not observed to react). The observed rates of reaction were independent of the presence of DNA indicating that the latter does not affect the availability of WR-1065 for reaction with Br2- radical. Reaction of WR-1065 with Br2- was used as a probe for determining the pK of the SH group. The rate of reaction increases from 1.8 X 10(8) M-1 s-1 at pH 6.3 to 1.6 X 10(9) M-1 s-1 at pH 8.4, the mid-point of the increase indicates a pK of 7.3.

UI MeSH Term Description Entries
D008624 Mercaptoethylamines Ethylamines, including CYSTEAMINE, that contain a sulfhydryl group in their structure.
D011675 Pulse Radiolysis Use of a pulse of X-rays or fast electrons to generate free radicals for spectroscopic examination. Radiolysis, Pulse
D011837 Radiation-Protective Agents Drugs used to protect against ionizing radiation. They are usually of interest for use in radiation therapy but have been considered for other purposes, e.g. military. Radiation Protectant,Radiation Protective Agent,Radiation-Protective Agent,Radiation-Protective Drug,Radioprotective Agent,Radioprotective Agents,Radioprotective Drug,Agents, Radiation-Protective,Radiation Protectants,Radiation Protective Agents,Radiation-Protective Drugs,Radiation-Protective Effect,Radiation-Protective Effects,Radioprotective Drugs,Agent, Radiation Protective,Agent, Radiation-Protective,Agent, Radioprotective,Agents, Radiation Protective,Agents, Radioprotective,Drug, Radiation-Protective,Drug, Radioprotective,Drugs, Radiation-Protective,Drugs, Radioprotective,Effect, Radiation-Protective,Effects, Radiation-Protective,Protectant, Radiation,Protectants, Radiation,Protective Agent, Radiation,Protective Agents, Radiation,Radiation Protective Drug,Radiation Protective Drugs,Radiation Protective Effect,Radiation Protective Effects
D001966 Bromine A halogen with the atomic symbol Br, atomic number 35, and atomic weight 79.904. It is a volatile reddish-brown liquid that gives off suffocating vapors, is corrosive to the skin, and may cause severe gastroenteritis if ingested. Bromine-79,Bromine 79
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations
D006878 Hydroxides Inorganic compounds that contain the OH- group.

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