UNLABELLED Current pretargeting systems use noncovalent biologic interactions, which are prone to immunogenicity. We previously developed a novel approach based on the bioorthogonal reaction between a radiolabeled tetrazine and an antibody-conjugated trans-cyclooctene (TCO). However, the tumor-to-blood ratio was low due to reaction with freely circulating antibody-TCO. METHODS Here we develop...

Unimolecular excited electronic state decomposition of novel high nitrogen content energetic molecules, such as 3,3(')-azobis(6-amino-1,2,4,5-tetrazine)-mixed N-oxides (DAATO(3.5)), 3-amino-6-chloro-1,2,4,5-tetrazine-2,4-dioxide (ACTO), and 3,6-diamino-1,2,4,5-tetrazine-1,4-dioxde (DATO), is investigated. Although these molecules are based on N-oxides of a tetrazine aromatic heterocyclic ring, ...

A convenient strategy to radiolabel a hydrazinonicotonic acid (HYNIC)-derived tetrazine with 99mTc was developed, and its utility for creating probes to image bone metabolism and bacterial infection using both active and pretargeting strategies was demonstrated. The 99mTc-labelled HYNIC-tetrazine was synthesized in 75% yield and exhibited high stability in vitro and in vivo. A trans-cyclooctene...

A new (18)F-labeled tetrazine derivative was developed aiming at optimal radiochemistry, fast reaction kinetics in inverse electron-demand Diels-Alder cycloaddition (IEDDA), and favorable pharmacokinetics for in vivo bioorthogonal chemistry. The radiolabeling of the tetrazine was achieved in high yield, purity, and specific activity under mild reaction conditions via conjugation with 5-[(18)F]f...

A novel amino acid derivative 3-(4-(1, 2, 4, 5-tetrazine-3-yl) phenyl)-2-aminopropanoic acid was synthesized in this study. The compound possessed better water-solubility and was synthesized more easily compared with the well-known and commercially available 3-(p-benzylamino)-1, 2, 4, 5-tetrazine. Tetrazine-containing amino acid showed excellent stability in biological media and might be used f...

Protocols have been achieved that permit facile introduction of s-tetrazine into unprotected peptides and the protein, thioredoxin, between two cysteine sulfhydryl groups (i.e., staple), followed by photochemical release (i.e., unstaple) and regeneration of the peptide/protein upon removal of the cyano groups from the derived bisthiocyanate. The S,S-tetrazine macrocycles in turn provide a conve...

A solid-phase synthesis of 5-aminopyrazole has been developed and applied to the preparation of pyrazolo[5,1-d][1,2,3,5]tetrazine-4(3H)-ones. In this strategy, a one-pot reaction from 5-aminopyrazoles to the pyrazolo[5,1-d][1,2,3,5]tetrazine-4(3H)-ones which provided the compounds in good yields was demonstrated. Using this synthetic strategy, we prepared a representative set of 16 pyrazolo[5,1...

One route to high density and high performance energetic materials based on 1,2,4,5-tetrazine is the introduction of 2,4-di-N-oxide functionalities. Based on several examples and through theoretical analysis, the strategy of regioselective introduction of these moieties into 1,2,4,5-tetrazines has been developed. Using this methodology, various new tetrazine structures containing the N-oxide fu...

A new electrofluorescent switch was prepared with an electroactive fluorescent tetrazine blend of polymer electrolyte; the cells contain four layers: the tetrazine polymer film, a photocured polymer electrolyte film, and two indium-tin oxide plates as the two contact electrodes.

The reactions of β-lactam carbenes with both 3,6-di(2-pyridyl)tetrazine and 3,6-di(4-pyridyl)tetrazine were studied. It was found that β-lactam carbenes reacted with 3,6-di(2-pyridyl)tetrazine to produce 5-triazolo[1,5-a]pyridylpyrrol-2-ones in good yields, while with 3,6-di(4-pyridyl)tetrazine, they afforded pyrido[c]cyclopenta[b]pyrrol-2-ones in moderate yields. Both reactions were proposed t...