Invited Talk 21st International Conference on Biological Inorganic Chemistry 2025

Chemical modification of biomolecules using hydrophilic olefin metathesis catalysts (121463)

Takashi Matsuo 1 , Tsubasa Kinugawa 1 , Seishu Mitsusada 1 , Naoki Orito 1 , Asuki Okada 1 , Naoki Akiyama 1 , Catur Jatmika 1
  1. Nara Institute of Science and Technology, Nara, Japan

 Chemical modification of biomolecules using transition metal complexes is a popular strategy for regioselective introduction of synthetic molecules into biomolecules. Olefin metathesis reaction (carbon-carbon rearrangement reaction) catalyzed by Hoveyda-Grubbs 2nd generation (HG-II)-type complexes is a potential candidate to achieve regioselective chemical modification of biomolecules. However, the hydrophobicity and reactivity reduction of the complexes in water often cause a difficulty in the chemical modification of biomolecules. We should address whether the ruthenium-olefin interaction, a key chemical event in HG-II-catalyzed olefin metathesis, works effectively in biochemical media.

 Recently, we reported ligand exchange reactions in nonpolar solvents between 2-alkoxybenzylide compounds and HG-II.[1] Accordingly, we have synthesized HG-II-type with hydrophilic groups and investigated whether the ligand exchange also occurs in protic solvents, using an olefin-labelled tripeptide.

 When HG-II was applied to Lys-Cys-Phe-OMe with an olefin moiety at the side chain of Cys residue in methanol, the NHC-coordinated ruthenium moiety was transferred onto the olefin moiety in the tripeptide with 80% yield. An HG-II-type complex with a cationic moiety accelerated the ruthenium complex transfer reaction. Furthermore, the complex transfer reaction was found to occur in aqueous media with 50-70% yields.[2] This result indicates that the ruthenium-olefin interaction also occurs in aqueous media. The ruthenium complex transfer was found to occur at olefin-modified cysteine residues on proteins. In fact, the ruthenium complex can be immobilized onto the protein through the ruthenium-olefin interactions. We also attempted interpeptide cross metathesis reactions catalyzed by the cationic HG-II-type complex and confirmed the reaction course. In these reactions, addition of chloride salt is essential for smooth reactions. [3]

 In conclusion, ruthenium-olefin interaction (one of the organometallic interactions) can work in aqueous media. Olefin metathesis can be used a method of biomolecule modification.[2,4]

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  1. [1] C. Jatmika et al., Dalton Trans. 2020, 49, 11618.; [2] C. Jatmika et al., Chem. Lett. 2020, 49, 1490.; [3] T. Matsuo et al., Organometallics. 2013, 32 5313.; [4] T. Matsuo, Catalysts, 2021, 11, 359.