Anionic Olefin Metathesis Catalysts Enable Modification of Unprotected Biomolecules in Water

Area of Science:

• Organometallic Chemistry
• Catalysis
• Chemical Biology

Background:

• Cationic olefin metathesis catalysts face stability challenges, limiting their application in chemical biology.
• Existing catalysts often exhibit poor water solubility and are incompatible with sensitive biomolecules.

Purpose of the Study:

• To develop robust, water-soluble anionic olefin metathesis catalysts.
• To enhance compatibility with biomolecules like DNA.
• To achieve high catalytic productivity under neutral pH conditions.

Main Methods:

• Design and synthesis of cyclic (alkyl)(amino) carbene (CAAC) ligands featuring a sulfonate tag.
• Incorporation of sulfonated CAAC ligands into Hoveyda-Grubbs type catalysts.
• Testing catalyst performance in the metathesis of unprotected carbohydrates and nucleosides in aqueous media.

Main Results:

• The novel anionic catalysts exhibit enhanced water-solubility and robustness against degradation.
• Hoveyda-Grubbs catalysts with sulfonated CAAC ligands achieve record productivity in carbohydrate and nucleoside metathesis at neutral pH.
• Decomposition of the anionic catalysts has minimal effect on metathesis selectivity, unlike rapidly degrading N-heterocyclic carbene (NHC) catalysts.

Conclusions:

• Anionic olefin metathesis catalysts with sulfonated CAAC ligands represent a significant advancement for applications in aqueous environments.
• These catalysts offer superior stability and compatibility with biomolecules compared to traditional NHC catalysts.
• The developed catalysts enable efficient metathesis of sensitive substrates like carbohydrates and nucleosides under mild, biologically relevant conditions.