Structure of transient radicals from cytostatic-active p-alkoxyphenols by continuous-flow EPR

Free Radic Biol Med. 1995 Nov;19(5):533-9. doi: 10.1016/0891-5849(95)00054-2.

Abstract

Para-alkoxyphenols are of medical significance as futural cytostatic drugs in antimelanoma chemotherapy. They take part in a radical redox-reaction in which the catalytically essential protein-linked tyrosyl radical in the functional subunit R2 of the growth-regulating enzyme ribonucleotide reductase (RR) is quenched. EPR spectroscopy has been employed in conjunction with a continuous-flow system to study the structure of transient radicals from p-alkoxyphenols with different alkyl chain lengths. Radicals of p-alkoxyphenols were generated by oxidation in a Fenton system (Ti3+/H2O2,pH1) after rapid mixing in a novel continuous-flow EPR cavity designed especially for low consumption of substance. Hyperfine structures identified by spectral simulation show that the structure of transient radicals from oxidized para-alkoxyphenols (methyl-, ethyl-, allyl-,propyl-,iso-propyl-, butyl-, iso-butyl-) belong to the type of phenoxyl radicals formed after abstraction of the OH proton. Hyperfine coupling constants are similar and vary only slightly with alkyl substituents.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use
  • Biotransformation
  • Electron Spin Resonance Spectroscopy / methods
  • Free Radicals
  • Humans
  • Melanoma / drug therapy
  • Oxidation-Reduction
  • Phenols / chemistry*
  • Phenols / metabolism
  • Phenols / therapeutic use
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Free Radicals
  • Phenols