Details
| Original language | English |
|---|---|
| Pages (from-to) | 7451-7454 |
| Number of pages | 4 |
| Journal | Chemical communications |
| Volume | 59 |
| Issue number | 48 |
| Publication status | Published - 23 May 2023 |
Abstract
We herein report a novel chemically triggered click-to-release system, that combines the trimethyl lock (TML) lactonization with the bioorthogonal inverse electron demand Diels-Alder (IEDDA) reaction of a vinyl ether and a tetrazine. Kinetic studies were carried out on a vinyl phenol model system with six tetrazines using NMR and UV/Vis spectroscopy, revealing that within the three step sequence the IEDDA reaction was rate-limiting. The reaction rates were enhanced by increasing the electrophilicity of the tetrazine, while balancing reactivity and stability of the tetrazines. The anticancer drug doxorubicin was conjugated to a vinyl-modified TML. Its subsequent liberation from vinyl-TML was triggered by dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate and followed quantitatively by NMR, thereby providing a proof-of-concept for the tetrazine/TML click-to-release system. In addition the applicability of the reaction under physiolgoical conditions could be shown.
ASJC Scopus subject areas
- Materials Science(all)
- Electronic, Optical and Magnetic Materials
- Chemical Engineering(all)
- Catalysis
- Materials Science(all)
- Ceramics and Composites
- Chemistry(all)
- Materials Science(all)
- Surfaces, Coatings and Films
- Materials Science(all)
- Metals and Alloys
- Materials Science(all)
- Materials Chemistry
Cite this
- Standard
- Harvard
- Apa
- Vancouver
- BibTeX
- RIS
In: Chemical communications, Vol. 59, No. 48, 23.05.2023, p. 7451-7454.
Research output: Contribution to journal › Article › Research › peer review
}
TY - JOUR
T1 - Tetrazine-induced activation of a trimethyl lock as a click-to-release system for protected doxorubicin
AU - Friederich, Julia
AU - Xu, Chunfa
AU - Raunft, Patrick
AU - Fuchs, Hazel L.S.
AU - Brönstrup, Mark
PY - 2023/5/23
Y1 - 2023/5/23
N2 - We herein report a novel chemically triggered click-to-release system, that combines the trimethyl lock (TML) lactonization with the bioorthogonal inverse electron demand Diels-Alder (IEDDA) reaction of a vinyl ether and a tetrazine. Kinetic studies were carried out on a vinyl phenol model system with six tetrazines using NMR and UV/Vis spectroscopy, revealing that within the three step sequence the IEDDA reaction was rate-limiting. The reaction rates were enhanced by increasing the electrophilicity of the tetrazine, while balancing reactivity and stability of the tetrazines. The anticancer drug doxorubicin was conjugated to a vinyl-modified TML. Its subsequent liberation from vinyl-TML was triggered by dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate and followed quantitatively by NMR, thereby providing a proof-of-concept for the tetrazine/TML click-to-release system. In addition the applicability of the reaction under physiolgoical conditions could be shown.
AB - We herein report a novel chemically triggered click-to-release system, that combines the trimethyl lock (TML) lactonization with the bioorthogonal inverse electron demand Diels-Alder (IEDDA) reaction of a vinyl ether and a tetrazine. Kinetic studies were carried out on a vinyl phenol model system with six tetrazines using NMR and UV/Vis spectroscopy, revealing that within the three step sequence the IEDDA reaction was rate-limiting. The reaction rates were enhanced by increasing the electrophilicity of the tetrazine, while balancing reactivity and stability of the tetrazines. The anticancer drug doxorubicin was conjugated to a vinyl-modified TML. Its subsequent liberation from vinyl-TML was triggered by dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate and followed quantitatively by NMR, thereby providing a proof-of-concept for the tetrazine/TML click-to-release system. In addition the applicability of the reaction under physiolgoical conditions could be shown.
UR - http://www.scopus.com/inward/record.url?scp=85161478756&partnerID=8YFLogxK
U2 - 10.1039/d3cc01334k
DO - 10.1039/d3cc01334k
M3 - Article
C2 - 37254691
AN - SCOPUS:85161478756
VL - 59
SP - 7451
EP - 7454
JO - Chemical communications
JF - Chemical communications
SN - 1359-7345
IS - 48
ER -