Related Experiment Video
Updated: May 14, 2026
10:39
Heterogeneous Removal of Water-Soluble Ruthenium Olefin Metathesis Catalyst from Aqueous Media Via Host-Guest Interaction
Published on: August 23, 2018
On-oligonucleotide olefin metathesis in water
Chun Zhang1, Christian O Blanco2, Anastasiya Khimich1
1Institute of Pharmacy and Food Chemistry, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Nature Communications
|May 12, 2026
Summary
Researchers developed a water-soluble ruthenium catalyst for synthesizing nucleic acid-tagged macrocycles using ring-closing metathesis (RCM). This breakthrough enables RCM in water for encoded library technologies and potential RNA-oligonucleotide drug development.
Area of Science:
- Chemical Biology
- Organic Chemistry
- Drug Discovery
Background:
- Genetically-encoded libraries are crucial for large-scale chemical screening.
- Synthetic macrocycles generated by ring-closing metathesis (RCM) show promise for targeting undruggable proteins.
- Previous limitations included catalyst incompatibility with nucleic acids and short catalyst lifetimes in aqueous environments.
Purpose of the Study:
- To develop a method for synthesizing nucleic acid-tagged macrocycles using RCM in neat water.
- To overcome the incompatibility issues between olefin metathesis catalysts and nucleic acids in aqueous conditions.
- To enable the application of RCM in water for encoded library technologies.
Main Methods:
- Synthesis of a novel anionic, water-soluble ruthenium catalyst.
- Application of the catalyst for RCM of nucleic acid-tagged substrates in neat water.
- Compatibility testing with various oligonucleotide tags (DNA, RNA, stabilized DNA).
Main Results:
- Successful synthesis of nucleic acid-tagged macrocycles via RCM in water.
- The ruthenium catalyst demonstrated high compatibility with diverse oligonucleotide tags.
- Useful conversions and efficient recovery of the nucleic acid components were achieved.
- The catalyst exhibited enhanced stability and lifetime in aqueous conditions.
Conclusions:
- The developed ruthenium catalyst facilitates RCM in neat water, overcoming previous limitations.
- This advance enables the use of RCM for encoded library technologies in aqueous media.
- The methodology holds potential for broader applications, including the development of RNA-oligonucleotide therapeutics.
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