Maximum quantity allowed is 999
trans-Cyclooctene (TCO) derivatives and 1,2,4,5-tetrazine (Tz) derivatives undergo highly selective and rapid reactions via the inverse electron-demand Diels–Alder (IEDDA) reaction. Compared to alkyne-azide click reactions (CuAAC, SPAAC), the IEDDA reaction proceeds faster, requires no metal catalysts, and exhibits excellent bioorthogonality.
Carbamate-modified TCO* (2-TCO) and certain Tz derivatives are known to release amine compounds following the IEDDA reaction, in what is called a "click-to-release" process. This click-to-release strategy has been applied to prodrug development and protein caging systems.
This reaction enables the controlled release of molecules at desired times and locations without the use of catalysts, owing to its highly selective and ultrafast click reactivity under physiological conditions. Importantly, this is a clean reaction, producing only N2 and CO2 as byproducts.
For preparation of TCO*-payloads, the axial isomer of TCO* is preferable. It has been reported that the axial isomer reacts via IEDDA approximately 150 times faster than the equatorial isomer.
In the release process following the IEDDA reaction, the substituents on the tetrazine (Tz) play a critical role. Among tetrazine derivatives, Me-Tz (3-methyl-1,2,4,5-tetrazine) is widely used. While H-Tz (1,2,4,5-tetrazine) undergoes IEDDA faster than Me-Tz, it is known to exhibit significantly reduced release efficiency afterward.
![[4-(6-Methyl-1,2,4,5-tetrazin-3-yl)phenyl]methanamine Hydrochloride](https://www.tcichemicals.com/assets/cms-images/click-to-release_reagents_M3558.png)
![[4-(6-Methyl-1,2,4,5-tetrazin-3-yl]phenyl)methanol](https://www.tcichemicals.com/assets/cms-images/click-to-release_reagents_M3469.png)
![3-[4-(Bromomethyl)phenyl]-6-methyl-1,2,4,5-tetrazine](https://www.tcichemicals.com/assets/cms-images/click-to-release_reagents_B6382.png)
