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Related Concept Videos

Phase II Reactions: Methylation Reactions01:17

Phase II Reactions: Methylation Reactions

680
Methylation is a phase II biotransformation process involving the attachment of a methyl group to a substrate. Enzymes known as methyltransferases orchestrate this reaction.
The mechanism of methylation unfolds in two stages. The first stage sees a methyltransferase enzyme facilitating the transfer of a methyl group from S-adenosylmethionine (SAM) to the substrate, forming S-adenosylhomocysteine (SAH). The second stage involves further metabolism of SAH into homocysteine, which can be recycled...
680

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Related Experiment Video

Updated: Jan 17, 2026

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
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Bioinspired transfer methylation enabled by a photoactive reagent.

Ding Zhang1,2, Weiqiu Liang3, Zhihan Zhang4

  • 1School of Science and Engineering, The Chinese University of Hong Kong, Shenzhen, Guangdong, China.

Nature Communications
|September 18, 2025
PubMed
Summary
This summary is machine-generated.

Researchers developed a novel biomimetic reagent for challenging radical methylation reactions. This photoactive tool enhances control over methyl radical transfer, enabling selective C-H methylation in complex molecules.

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Area of Science:

  • Organic Chemistry
  • Biomimetic Chemistry
  • Synthetic Methodology

Background:

  • Radical methylation is crucial in chemistry and biology but faces challenges with unstable intermediates, low reactivity, and poor selectivity.
  • Existing methods struggle with precise control over methyl radical generation and transfer.

Purpose of the Study:

  • To develop a photoactive, biomimetic reagent for overcoming challenges in radical methylation.
  • To enable direct and selective C(sp2)-H methylation across diverse heteroarenes.

Main Methods:

  • Utilized a bulky and stabilized α-aminomethyl radical for enhanced control.
  • Developed a bioinspired transfer methylation protocol.
  • Investigated mechanistic pathways using addition-elimination sequences.

Main Results:

  • Achieved direct and selective C(sp2)-H methylation of various heteroarenes, including complex drug molecules.
  • Successfully performed the challenging C4-methylation of free quinolines.
  • Demonstrated balanced reactivity and selectivity through mechanistic studies.

Conclusions:

  • The novel α-aminomethyl radical reagent offers enhanced control over radical generation and transfer.
  • The bioinspired protocol provides a powerful tool for selective C-H methylation, mimicking natural methyltransferases.
  • This approach broadens the scope of methylation reactions, particularly for complex heterocyclic systems.