A Ruthenium(CAAC‐5) Olefin Metathesis Catalyst for Bioconjugation
- 1Department of Chemistry University of Basel Basel Switzerland
- 2Swiss Nanoscience Institute University of Basel Basel Switzerland
- 3National Centre of Competence in Research Molecular Systems Engineering (NCCR MSE) University of Basel Basel Switzerland
Abstract
Olefin metathesis is a powerful transformation for carbon–carbon bond formation, yet its application in biological settings is challenged by the instability of most ruthenium catalysts in aqueous media. Herein, we report a Ru(CAAC‐5) olefin metathesis catalyst bearing a functional handle for bioconjugation. The resulting hybrid catalyst catalyzes ring‐closing metathesis (RCM) and displays extended lifetimes in aqueous media. Functionalized CAAC‐5 ligands bearing a protected aniline linker were prepared via enamine alkylation and coordinated to ruthenium to afford the corresponding Ru(CAAC‐5) complex. In a benchmark RCM reaction under biologically relevant conditions, the ruthenium complex exhibits enhanced catalytic robustness and reaches turnover numbers of up to 600. Deprotection of an amine‐functionalized handle enables the bioconjugation to proteins and peptides. Using this platform, the catalyst was anchored to biomolecules through supramolecular anchoring to human carbonic anhydrase II (hCA II), click conjugation to peptides (SS01), and covalent attachment to ubiquitin (Ubi). To the best of our knowledge, this aniline‐functionalized Ru(CAAC‐5) complex is the first CAAC‐bearing metathesis catalyst amenable to bioconjugation, while retaining the prolonged catalytic activity characteristic of CAAC‐based systems in aqueous media.
Related
- Structure Determination of Surface Sites in Heterogeneous Olefin Metathesis Catalysts from 95Mo NMR Signatures
- Light-driven metal-free thiocarbonyl – olefin metathesis: a general route to sterically hindered alkenes
- Atmospheric pressure water-gas shift reaction and transfer hydrogenation of ketones using a ruthenium pincer catalyst.
- Electrochemical Tryptophan-Selective Bioconjugation in Neutral Buffer via Cooperative N -Oxyl Radicals
- Electrospray Mass Spectrometric Characterization of Novel Unsaturated Neutral Carbohydrate Bolaforms Obtained by Catalytic Metathesis
BibTeX
@article{graf2026rutheniumcaac5,
title = {{A Ruthenium(CAAC‐5) Olefin Metathesis Catalyst for Bioconjugation}},
author = {Damian Alexander Graf and Mikhail Boym and María Álvarez and Tsvetan Kardashliev and Thomas R. Ward},
journal = {Angewandte Chemie (International Ed. in English)},
year = {2026},
month = sep,
doi = {10.1002/anie.3685338},
url = {https://doi.org/10.1002/anie.3685338},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A Ruthenium(CAAC‐5) Olefin Metathesis Catalyst for Bioconjugation
AU - Damian Alexander Graf
AU - Mikhail Boym
AU - María Álvarez
AU - Tsvetan Kardashliev
AU - Thomas R. Ward
PY - 2026
DA - 2026/09/21
JO - Angewandte Chemie (International Ed. in English)
DO - 10.1002/anie.3685338
UR - https://doi.org/10.1002/anie.3685338
AB - Olefin metathesis is a powerful transformation for carbon–carbon bond formation, yet its application in biological settings is challenged by the instability of most ruthenium catalysts in aqueous media. Herein, we report a Ru(CAAC‐5) olefin metathesis catalyst bearing a functional handle for bioconjugation. The resulting hybrid catalyst catalyzes ring‐closing metathesis (RCM) and displays extended lifetimes in aqueous media. Functionalized CAAC‐5 ligands bearing a protected aniline linker were prepared via enamine alkylation and coordinated to ruthenium to afford the corresponding Ru(CAAC‐5) complex. In a benchmark RCM reaction under biologically relevant conditions, the ruthenium complex exhibits enhanced catalytic robustness and reaches turnover numbers of up to 600. Deprotection of an amine‐functionalized handle enables the bioconjugation to proteins and peptides. Using this platform, the catalyst was anchored to biomolecules through supramolecular anchoring to human carbonic anhydrase II (hCA II), click conjugation to peptides (SS01), and covalent attachment to ubiquitin (Ubi). To the best of our knowledge, this aniline‐functionalized Ru(CAAC‐5) complex is the first CAAC‐bearing metathesis catalyst amenable to bioconjugation, while retaining the prolonged catalytic activity characteristic of CAAC‐based systems in aqueous media.
SN - 1433-7851
SN - 1521-3773
ER -