Free Radical Chemistry

Free radicals are neutral species bearing one or more unpaired electrons. Their unique reactivity underpins an extraordinary range of bond‐forming and bond‐cleavage processes, from organic synthesis to biological signalling. Radical reactions often proceed under mild conditions via homolytic bond cleavage, photochemical activation or single‐electron transfer (SET). The resulting radicals engage in addition to unsaturated bonds, hydrogen‐atom transfer (HAT), chain‐propagation cycles and selective coupling with polar partners. Advances in catalyst development have transformed radical chemistry into a versatile toolkit, enabling controlled polymerisation methods such as reversible addition–fragmentation chain transfer (RAFT) and atom transfer radical polymerisation (ATRP), precision modifications of biomolecules and late‐stage functionalisation of complex scaffolds. Radical pathways offer complementary selectivity to polar reactions, broad functional-group tolerance and reduced waste, and they continue to inspire innovations in material science, sustainable synthesis and chemical biology.

Research from Nature Portfolio

In 2022, an electrocatalytic strategy was introduced for cobalt‐mediated hydrogen‐atom transfer processes that functionalise a wide range of alkenes. By optimising electrochemical generation of a Co–H species, unactivated olefins undergo hydrofunctionalisation with exceptional chemoselectivity and tunable reactivity, obviating the need for silane or peroxide reagents and enabling diverse C(sp³)–C(sp³) and C–X bond formations under mild conditions. This work leverages paired electrochemical‐radical cycles to access densely functionalised targets and illustrates radical electrosynthesis as a green route to complex molecules. More recently, a population‐based heteropolymer design paradigm has translated segmental sequence patterns from natural proteins into synthetic radical polymers. By encoding statistical monomer arrangements in disordered, partially folded and folded segments, multicomponent radical polymerisations yield heteropolymer ensembles that mimic key fluid functions—chaperone activity, thermal stabilisation and reversible self-assembly—offering a blueprint for radical-mediated materials that emulate biological complexity.

Research from all publishers

Photocontrolled RAFT polymerisation has emerged as a powerful approach for precision radical polymer synthesis under visible-light irradiation. Recent reviews highlight how photoiniferter, photoinduced electron/energy-transfer RAFT and photoredox-catalysed systems deliver spatiotemporal control, oxygen tolerance and low-energy operation, while mechanistic studies unravel activation–deactivation equilibria and guide catalyst design for improved efficiency and scale-up. In parallel, novel radical cross-coupling methodologies have harnessed photocatalytic and thiol co-catalysed cycles to stitch feedstock olefins into sp³-rich scaffolds. By generating alkyl radicals from electron-poor alkenes under mild photoredox conditions and trapping them with neutral alkenes, this reductive strategy forges C–C bonds in a modular fashion, expanding the scope of radical disconnection patterns for rapid assembly of complex architectures.

Free Radical Chemistry publication trend

The graph below shows the total number of articles in free radical chemistry across all publications each year (not limited to Nature Index journals).

Technical terms

Free radical: A species with one or more unpaired electrons, typically generated by homolytic bond cleavage or single-electron transfer.

Single-electron transfer (SET): A mechanism in which one electron moves between species, producing radical ions that initiate radical reactions.

Hydrogen-atom transfer (HAT): A radical process in which a hydrogen atom (proton plus electron) transfers between two molecules, forming free radicals.

RAFT polymerisation: A controlled radical polymerisation technique using thiocarbonylthio chain-transfer agents to mediate reversible addition–fragmentation, achieving narrow dispersities and block copolymer architectures.

Atom transfer radical polymerisation (ATRP): A method employing reversible halogen atom transfer between a metal complex and polymer chain ends, enabling precise control of molar mass and structure.

Photoredox catalysis: Use of light-activated catalysts to mediate single-electron transfers and generate radicals under mild conditions with high functional-group tolerance.

References

1. Free-Radical Reactions.
2. Cobalt-electrocatalytic HAT for functionalization of unsaturated C–C bonds. Nature (2022).
3. Population-based heteropolymer design to mimic protein mixtures. Nature (2023).
4. Photocontrolled RAFT polymerization: past, present, and future. Chemical Society Reviews (2023).