Some Reactions and Properties of Nitro Radical-Anions Important in Biology and Medicine

Nitroaromatic compounds, ArNO2have widespread actual or potential use in medicine and cancer therapy. There is direct proof that free-radical metabolites are involved in many applications, and an appreciation of the conceptual basis for their therapeutic differential; however, an understanding of th...

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Bibliographic Details
Published in:Environmental health perspectives 1985-12, Vol.64, p.309-320
Main Author: Wardman, Peter
Format: Article
Language:English
Subjects:
Anions
Antineoplastic Agents
Chemical Phenomena
Chemistry
Electron paramagnetic resonance
Electron transfer
Electron Transport
Electrons
Free Radicals
Humans
Hypoxia
Kinetics
Monograph on Free Radical Metabolites of Toxic Chemcials, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709
Neoplasms - drug therapy
Nitro compounds
Nitro Compounds - therapeutic use
Oxidation-Reduction
Oxygen
Radiolysis
Structure-Activity Relationship
Superoxides
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Summary:Nitroaromatic compounds, ArNO2have widespread actual or potential use in medicine and cancer therapy. There is direct proof that free-radical metabolites are involved in many applications, and an appreciation of the conceptual basis for their therapeutic differential; however, an understanding of the detailed mechanisms involved is lacking. Redox properties control most biological responses of nitro compounds, and the characteristics of the one-electron couple: ArNO2/ ArNO2 -are detailed. The "futile metabolism" of nitroaryl compounds characteristic of most aerobic nitroreductase systems reflects competition between natural radical-decay pathways and a one-electron transfer reaction to yield superoxide ion, O2 -. Prototropic properties control the rate of radical decay, and redox properties control the rate of electron transfer to O2or other acceptors. There are clear parallels in the chemistry of ArNO2 -and O2 -. While nitro radicals have frequently been invoked as damaging species, they are very unreactive (except as simple reductants). It seems likely that reductive metabolism of nitroaryl compounds, although generally involving nitro radical-anions as obligate intermediates (and this is required for therapeutic selectivity towards anaerobes), results in biological damage via reductive metabolites of higher reduction order than the one-electron product.
ISSN:0091-6765
1552-9924
DOI:10.1289/ehp.8564309