Chemiluminescent probe for the detection of inverse electron demand Diels-Alder reaction between tetrazine and trans-Cyclooctene

Bioorg Med Chem. 2021 Oct 1:47:116400. doi: 10.1016/j.bmc.2021.116400. Epub 2021 Sep 8.

Abstract

A chemiluminescent probe has been developed, consisting of phenoxy-dioxetane moiety covalently attached to trans-cyclooctene. The inverse electron demand Diels-Alder reaction with tetrazine produces a cycloaddition product which undergoes a series of spontaneous rearrangements resulting in emission of green light. The chemiluminescent probe can be applied to study bioconjugation chemistry with tetrazine-modified biomaterials, which have recently been shown to have great potential for anticancer drug delivery. This work describes in vitro studies, including NMR and spectroscopic investigation of chemiluminescence, which will pave way for future in vivo bioconjugation experiments.

Keywords: Bioconjugation; Chemiluminescence; IEDDA; TCO; Tetrazine; Trans-cyclooctene; Tz.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aza Compounds / chemistry*
  • Benzene Derivatives / chemistry*
  • Cycloaddition Reaction
  • Cyclooctanes / chemistry*
  • Heterocyclic Compounds, 1-Ring / chemical synthesis
  • Heterocyclic Compounds, 1-Ring / chemistry*
  • Molecular Probes / chemical synthesis
  • Molecular Probes / chemistry*
  • Molecular Structure

Substances

  • 1,2,4,5-tetrazine
  • Aza Compounds
  • Benzene Derivatives
  • Cyclooctanes
  • Heterocyclic Compounds, 1-Ring
  • Molecular Probes
  • 1,2-dioxetane