Norbornene Click Chemistry

Norbornene (NBE) click reagents are designed for copper-free bioorthogonal conjugation with tetrazines through the inverse electron-demand Diels-Alder (IEDDA) reaction. With the chemical formula C7H10, norbornene consists of a strained alkene that is highly reactive with tetrazines, thiols, and other strong oxidizing agents. This provides a reactive handle that can be incoporated into various biomolecules for subsequent labeling and tagging. Physically, norbornene is a white organic compound with a strong unpleasant smell.

Key features:

• Fast and selective: norbornene groups undergo fast and selective “click” reactions with tetrazines through IEDDA cycloaddition
• Copper free: no Cu(I) catalyst required
• Bioorthogonal: compatible with living biological systems and organisms
• Versatile functionalization: available with different linkers

In an application of norbornene click chemistry, Woolley et al. (2025) developed lanthanide-tetrazine complexes that combined imaging capabilities in gadolinium, europium, and terbium probes and tetrazine-functionalized ligands that could provide MRI contrast. This was successfully conjugated with a norbornene-functionalized peptide that could create a bioorthogonal complex for targeting living tissue. Specifically, the blood brain barrier represents an attractive target for such modalities.

In another paper by Alves et al. (2022), researchers demonstrated the use of thiol–norbornene photoclick chemistry to functionalize chitosan with antimicrobial peptides, highlighting norbornene’s ability to create functional biomaterials. The resulting materials showed enhanced antibacterial activity against both Gram-positive and Gram-negative bacteria while maintaining good biocompatibility with human fibroblasts. The work highlights norbornene photoclick chemistry as a versatile, efficient approach for site-specific biomolecule conjugation and the development of functional antimicrobial materials.

Our norbornene reagents are available in a variety of functionalized formats, providing researchers with convenient building blocks for protein labeling, biomolecule conjugation, lipid modification, hydrogel formation, and molecular imaging.

References:

Alves, P. M., Pereira, R. F., Costa, B., Tassi, N., Teixeira, C., Leiro, V., … & Martins, M. C. L. (2022). Thiol–norbornene photoclick chemistry for grafting antimicrobial peptides onto chitosan to create antibacterial biomaterials. ACS Applied Polymer Materials, 4(7), 5012-5026.

Woolley, B., Wu, Y., Xiong, L., Chau, H. F., Zhang, J., Law, G. L., … & Long, N. J. (2025). Lanthanide–tetrazine probes for bio-imaging and click chemistry. Chemical science, 16(8), 3588-3597.

See Click Bioprobe’s list of norbornene reagents: