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PHOTOSENSITIZATION OF ANTICANCER AGENTS‐8. ONE‐ELECTRON REDUCTION OF MITOXANTRONE: AN EPR AND SPECTROPHOTOMETRIC STUDY
Author(s) -
Reszka Krzysztof,
Lown J. William
Publication year - 1989
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/j.1751-1097.1989.tb04163.x
Subject(s) - chemistry , mitoxantrone , electron paramagnetic resonance , photochemistry , semiquinone , protonation , one electron reduction , radical , electron donor , solvated electron , electron transfer , aqueous solution , photosensitizer , reaction rate constant , quinone , kinetics , stereochemistry , organic chemistry , radiolysis , electrochemistry , nuclear magnetic resonance , ion , quantum mechanics , catalysis , medicine , physics , surgery , electrode , chemotherapy
— An efficient method of one‐electron reduction of the anticancer agent mitoxantrone is described. The method depends on illumination of a suitable photosensitizer absorbing blue light [acriflavine, anthrapyrazole, or Ru(bpy) + ] in the presence of the drug and an electron donor, such as NAD(P)H, in deaerated solutions. An EPR spectrum, assigned to a semiquinone of mitoxantrone, is generated under these conditions and identified by spectral simulation. Decay of this species, attributed to a radical‐radical reaction, gives a second order rate constant of 1.7 10 2 M ‐1 s ‐1 in organic media [dimethylsulfoxide (DMSO)/pH 8 buffer, 1:1 vol/vol] but is more rapid (˜10 4 M ‐1 s ‐1 ) in aqueous media under comparable conditions. The considerably decreased lifetime of the mitoxantrone radical at pH 5 is attributed to an additional electron transfer, promoted by protonation of the radical, and/or to an accelerated recombination of neutral radicals, leading to an EPR‐silent species. Parallel spectrophotometric studies on the generation of the mitoxantrone reduced species by photosensitized reduction are described. The method offers convenient access to a key radical species involved in the metabolism and possible mode of action of this clinical anticancer agent.