University of Delaware OEIP
University of Delaware

Enzyme, Light and Catalytic Methods and Reagents for Inducing Bioorthgonal Reactivity

Technology #ud16-23

Questions about this technology? Ask a Technology Manager

Download Printable PDF

Image Gallery
Dr. Joseph Fox
Research in the Fox group centers on the development of new types of chemical reactions, the application of these new reactions to the synthesis of naturally occurring and designed molecules with biological function, and in the use of design concepts in organic synthesis for applications in biology and materials science.
External Link (
Xinqiao Jia
Colin Thorpe
Dr. Joel Rosenthal
The Rosenthal Research Group focuses on solving problems related to the environment, renewable energy storage/conversion and human health.
External Link (
Han Zhang
Yinshi Fang
Will Trout
Managed By
Yops Brad
Director, Technology Transfer Center 3028310147
Patent Protection

Methods for inducing bioorthogonal reactivity

PCT Patent Application WO 2017/106427
Rapid Bioorthogonal Chemistry Turn-on through Enzymatic or Long Wavelength Photocatalytic Activation of Tetrazine Ligation
Journal of American Chemical Society, J. Am. Chem. Soc. 2016, 138, 5978−5983

Technology Description:

Bioorthogonal chemistry has evolved into a field with broad reaching applications in biology, medicine and materials science. The inverse-electron demand Diels-Alder reaction of s-tetrazines with alkene or alkyne dienophiles, referred to as tetrazine ligation, is a prominent tool in the biorthogonal toolbox. A notable aspect of the tetrazine ligation are the exceptionally high rates of reactivity that can be achieved in simple biomolecular reactions. Scientists at the University of Delaware have developed a new avenue for this reaction wherein biorthogonal reactivity is turned on by a controllable, catalytic stimulus. Either visible light and a long wavelength sensitizer, or very low loadings of horseradish peroxidase are used to catalyze the oxidation of a dihydrotetrazine to a tetrazine. This method can have broad applications in pretargeted drug delivery and photodynamic therapy.


  • The new method represents the first way to 'turn on' the tetrazine ligation using visible/Near IR light, or through catalysis (enzymatic or unnatural).  
  • This process is distinct as the dihydrotetrazine/tetrazine pair used has high stability towards both oxygen and water. 
  • This process eliminates the background chemistry, thus making the drug delivery process safer.


  • Pretargeted drug delivery 
  • Photodynamic therapy