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Updated: Jan 20, 2026
01:16
Radical Reactivity: Nucleophilic Radicals
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Radical-Stimulated Nucleophile Release
1EaStCHEM School of Chemistry , University of St. Andrews , St. Andrews , Fife KY16 9ST , United Kingdom.
The Journal of Organic Chemistry
|September 6, 2019
Summary
Radicals adjacent to positive charges can enhance inverse heterolytic dissociation, facilitating nucleophile release. This effect is stronger with carbon-centered radicals and has implications for DNA/RNA strand scission.
Area of Science:
- Organic Chemistry
- Computational Chemistry
- Biochemistry
Background:
- Radical centers are known to enhance deprotonation.
- Inverse heterolytic dissociation releases nucleophiles, unlike typical heterolytic dissociation.
Purpose of the Study:
- To investigate if radicals can stimulate inverse heterolytic dissociations.
- To assess the impact of radical proximity and type on dissociation enhancement.
Main Methods:
- Density Functional Theory (DFT) calculations were used.
- Free energies of heterolytic dissociations were assessed.
- Various radical-containing precursors were computationally examined.
Main Results:
- Radicals adjacent to incipient positive charges generally enhanced heterolytic dissociation.
- Carbon-centered radicals showed greater enhancement than oxygen-centered radicals.
- Specific precursors (fluorenylmethyl, cyclohepta-2,4,6-trienylmethyl) enabled exergonic nucleophile release.
- Enhanced heterolytic phosphate release from nucleotide C4' radicals was observed, supporting DNA/RNA strand breaking mechanisms.
- Resonance stabilization of radical-cations was identified as the key promoting factor.
Conclusions:
- Suitably sited radicals can significantly enhance inverse heterolytic dissociation.
- This mechanism is relevant to radical-induced DNA and RNA strand breaking.
- Understanding these effects aids in designing molecules with controlled dissociation properties.
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