Selective Ligand Replacement Leads to Carbene Complexes as Catalysts in Proteins
- 1Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, United Kingdom, CB2 1EW
Abstract
Artificial metalloenzymes (ArMs) that incorporate organometallic fragments through direct metal–protein coordination open the door to unlock the full evolutionary potential of the protein scaffold to modulate catalysis. This work builds on our previously published work, in which Ru(II) piano stool complexes bearing bipyridyl ligands were used to deliver [Ru(Arene)]2+ fragments into a naïve protein scaffold, generating a transfer-hydrogenase artificial metalloenzyme. Here we systematically explore Ru(II) piano stool complexes bearing pyridyl–N-heterocyclic carbene (Pyr–NHC) bidentate ligands as active-site precursors for metathases and transfer hydrogenases. In this work we describe the synthesis and characterisation of five novel Ru(II) piano stool complexes bearing a hexamethylbenzene (HMB) arene cap and Pyr–NHC bidentate ligands, in which systematic variation of the NHC wingtip substituent (R′ = Me, Et, iPr, Ph) and the pyridine ring substituent (R = H, F) tunes the steric and electronic properties of the complex. Single-crystal X-ray analysis and electrochemical studies show that the strong σ-donation from the carbene lowers the Ru(II/III) redox potential and elongates the Ru–HMB bond relative to their bipyridyl counterparts. This supports displacement of the arene as opposed to the bidentate ligand in the presence of protein. Systematic comparison between Pyr–NHC and bipyridyl complexes also provided an insight into the influence of the arene and the bidentate ligand on the structural and electrochemical properties of these complexes.
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BibTeX
@misc{flores2026selective,
title = {{Selective Ligand Replacement Leads to Carbene Complexes as Catalysts in Proteins}},
author = {Armando Albert Flores and Matthew G. Wheeler and Oskar James Klein and George S. Biggs and Jonathan Shaw and Jonathan Bostock and Victoria Daramy-Williams and Max Lambert and Natasha Usselmann and Andrew D. Bond and Sally R. Boss and Paul D. Barker},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15010193/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010193/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Selective Ligand Replacement Leads to Carbene Complexes as Catalysts in Proteins
AU - Armando Albert Flores
AU - Matthew G. Wheeler
AU - Oskar James Klein
AU - George S. Biggs
AU - Jonathan Shaw
AU - Jonathan Bostock
AU - Victoria Daramy-Williams
AU - Max Lambert
AU - Natasha Usselmann
AU - Andrew D. Bond
AU - Sally R. Boss
AU - Paul D. Barker
PY - 2026
DA - 2026/10/09
PB - ChemRxiv
DO - 10.26434/chemrxiv.15010193/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010193/v1
AB - Artificial metalloenzymes (ArMs) that incorporate organometallic fragments through direct metal–protein coordination open the door to unlock the full evolutionary potential of the protein scaffold to modulate catalysis. This work builds on our previously published work, in which Ru(II) piano stool complexes bearing bipyridyl ligands were used to deliver [Ru(Arene)]2+ fragments into a naïve protein scaffold, generating a transfer-hydrogenase artificial metalloenzyme. Here we systematically explore Ru(II) piano stool complexes bearing pyridyl–N-heterocyclic carbene (Pyr–NHC) bidentate ligands as active-site precursors for metathases and transfer hydrogenases. In this work we describe the synthesis and characterisation of five novel Ru(II) piano stool complexes bearing a hexamethylbenzene (HMB) arene cap and Pyr–NHC bidentate ligands, in which systematic variation of the NHC wingtip substituent (R′ = Me, Et, iPr, Ph) and the pyridine ring substituent (R = H, F) tunes the steric and electronic properties of the complex. Single-crystal X-ray analysis and electrochemical studies show that the strong σ-donation from the carbene lowers the Ru(II/III) redox potential and elongates the Ru–HMB bond relative to their bipyridyl counterparts. This supports displacement of the arene as opposed to the bidentate ligand in the presence of protein. Systematic comparison between Pyr–NHC and bipyridyl complexes also provided an insight into the influence of the arene and the bidentate ligand on the structural and electrochemical properties of these complexes.
ER -