Biomedical Aspects of Ion-Radical Organic Chemistry

A snbstantial body of experimental evidence indicates that the formation of a covalent bond between chemical carcinogens and cellnlar macromolecnles represents the first critical step in the multistage process, eventually leading to tumor formation (see Geacintov et al. 1997, references therein). Most chemical carcinogens are not active on their own, but require metabolic activation to produce reactive intermediates capable of binding covalently with target macromolecnles, particularly with deoxyribonucleic acid (DNA), and thereby, initiate cancer. 

The reason that one-electron oxidation is suggested as playing a central role in the metabolic activation of PAHs concerns certain features of the cation-radicals that are common to the most potent carcinogens of the family. 

Relatively low IP, which allows metabolic removal of one electron with the formation of a relatively stable cation-radical 

Charge localization in the cation-radical that renders this intermediate specifically and efficiently to react with nucleophiles 

Optimal geometric configuration that allows the formation of appropriate intercalating physical complexes with DNA, thus favoring metabolic activation and the formation of covalent bonds with DNA nucleophiles 

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