Copper-free click for PET: Rapid 1,3-dipolar cycloadditions with a fluorine-18 cyclooctyne

Richard D. Carpenter, Sven H. Hausner, Julie Sutcliffe

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

The strain-promoted click 1,3-dipolar cycloaddition reactions involving azides and cyclooctynes for the synthesis of triazoles offer the advantage of being able to be performed in biological settings via copper-free chemistries. While strained reagents conjugated to optical dyes and radiometal conjugates have been reported, cyclooctyne reagents labeled with fluorine-18 ( 18F) and radiochemically evaluated in a copper-free click reaction have yet to be explored. This report describes the conversion of a bifunctional azadibenzocyclooctyne (ADIBO) amine to the 18F-labeled cyclooctyne 4, the subsequent fast copper-free 1,3-dipolar cycloaddition reaction with alkyl azides at 37 °C (>70% radiochemical conversion in 30 min), and biological evaluations (serum stability of >95% at 2 h). These findings demonstrate the excellent reactivity of the 18F-labeled cyclooctyne 4 with readily available azides that will allow future work focusing on rapid copper-free in vitro and in vivo click chemistries for PET imaging using 18F-labeled cyclooctyne derivatives of ADIBO.

Original languageEnglish (US)
Pages (from-to)885-889
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume2
Issue number12
DOIs
StatePublished - Dec 8 2011

Fingerprint

Cycloaddition
Fluorine
Cycloaddition Reaction
Azides
Copper
Click Chemistry
Triazoles
Amines
Coloring Agents
Derivatives
Imaging techniques
Serum

Keywords

  • Copper-free click chemistry
  • cycloaddition
  • cyclooctyne
  • fluorine-18
  • positron emission tomography

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Biochemistry

Cite this

Copper-free click for PET : Rapid 1,3-dipolar cycloadditions with a fluorine-18 cyclooctyne. / Carpenter, Richard D.; Hausner, Sven H.; Sutcliffe, Julie.

In: ACS Medicinal Chemistry Letters, Vol. 2, No. 12, 08.12.2011, p. 885-889.

Research output: Contribution to journalArticle

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