Free radicals in quinone-containing antitumor agents. Electrochemical reduction of diaziquone (2,5-diaziridine-3,6-bis(carboethoxyamino)-1,4 -benzoquinone) and two analogues.
The one-electron electrochemical reduction of diaziquone was analyzed using electron spin resonance and compared to its enzymatic reduction. Two analogues were used to help the analysis. The analogues contained chlorine atoms which substituted either the carboethoxyamino groups or the aziridine groups of the parent compound. The diaziquone free radical produced electrochemically in dimethyl sulfoxide exhibited an 11-line electron spin resonance spectrum. The hyperfine couplings responsible for this spectrum were due to the aziridine nitrogens (aNAz), and the imide hydrogens (aHNHR) and nitrogens (aNNHR) of the carboethoxyamino groups. The couplings had the following order of strength: (aNAz) greater than (aHNHR) greater than (aNNHR). The nuclei responsible for the (aNAz) and (aHNHR) coupling were found to be magnetically inequivalent. Adding water to the dimethyl sulfoxide solution of electrochemically reduced diaziquone changed its 11-line ESR spectrum to a 5-line spectrum identical to the one observed for enzymatically reduced diaziquone. Hence, the identity of this latter free radical was resolved. Electrochemically reduced free radicals of antitumor agents can be used to understand biologically reduced ones and thus explore drug activity-free radical structure relationships.
D000818:Animals; D000970:Antineoplastic Agents; D001388:Aziridines / Q000378:metabolism; D001389:Azirines / Q000378:metabolism; D016227:Benzoquinones; D004121:Dimethyl Sulfoxide; D004563:Electrochemistry; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D008862:Microsomes, Liver / Q000201:enzymology; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010084:Oxidation-Reduction; D011809:Quinones / Q000378:metabolism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001388:Aziridines; D001389:Azirines; D016227:Benzoquinones; D005609:Free Radicals; D011809:Quinones; C043462:NSC 191295; C043461:NSC 30705; D009251:NADPH-Ferrihemoprotein Reductase; C029108:diaziquone; D004121:Dimethyl Sulfoxide