Abstract
The tetrazine ligation is one of the fastest bioorthogonal ligations and plays a pivotal role in time-critical in vitro and in vivo applications. However, prediction of the reactivity of tetrazines in inverse electron demand Diels–Alder-initiated ligation reactions is not straight-forward. Commonly used tools such as frontier molecular orbital theory only give qualitative and often even wrong results. Applying density functional theory, we have been able to develop a simple computational method for the prediction of the reactivity of aryl/alkyl-substituted tetrazines in inverse electron demand Diels–Alder reactions.Graphical
Highlights
Tetrazine ligations (TLs) are bioorthogonal inverse electron demand Diels–Alder (IEDDA) initiated cycloadditions proceeding with exceptional high second-order rates of up to 3,300,000 M-1 s-1 [1]
In TLs, an 1,2,4,5-tetrazine (Tz) reacts with an electron-rich dienophile in an IEDDA reaction followed by cycloreversion under the loss of nitrogen (Fig. 1)
We have investigated the reactivity of several 3-aryl-6-(3-fluoropropyl)-1,2,4,5-tetrazines 1–8 as chemical probes for rapid radiolabeling and pretargeted PET
Summary
Tetrazine ligations (TLs) are bioorthogonal inverse electron demand Diels–Alder (IEDDA) initiated cycloadditions proceeding with exceptional high second-order rates of up to 3,300,000 M-1 s-1 [1]. In TLs, an 1,2,4,5-tetrazine (Tz) reacts with an electron-rich dienophile in an IEDDA reaction followed by cycloreversion under the loss of nitrogen (Fig. 1). Strained alkenes such as norbornenes [2, 3], cyclopropenes [4, 5], and trans-cyclooctenes (TCOs) [1, 6,7,8] are commonly used dienophiles, with TCOs providing the highest reactivity.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
