Structure-function relationships in aryl diazirines reveal optimal design features to maximize C-H insertion

Stefania F. Musolino, Zhipeng Pei, Liting Bi, Gino A. DiLabio, Jeremy E. Wulff

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)
8 Downloads (Pure)


Diazirine reagents allow for the ready generation of carbenes upon photochemical, thermal, or electrical stimulation. Because carbenes formed in this way can undergo rapid insertion into any nearby C-H, O-H or N-H bond, molecules that encode diazirine functions have emerged as privileged tools in applications ranging from biological target identification and proteomics through to polymer crosslinking and adhesion. Here we use a combination of experimental and computational methods to complete the first comprehensive survey of diazirine structure-function relationships, with a particular focus on thermal activation methods. We reveal a striking ability to vary the activation energy and activation temperature of aryl diazirines through the rational manipulation of electronic properties. Significantly, we show that electron-rich diazirines have greatly enhanced efficacy toward C-H insertion, under both thermal and photochemical activation conditions. We expect these results to lead to significant improvements in diazirine-based chemical probes and polymer crosslinkers.

Original languageEnglish
Pages (from-to)12138-12148
Number of pages11
JournalChemical Science
Issue number36
Publication statusPublished - 28 Sept 2021
Externally publishedYes


  • Structure-function relationship
  • aryl diazirines
  • C-H insertion
  • carbenes
  • diazirine reagents


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