6 publications

6 publications

A Highly Active Biohybrid Catalyst for Olefin Metathesis in Water: Impact of a Hydrophobic Cavity in a β-Barrel Protein

Okuda, J.

ACS Catal. 2015, 5, 7519-7522, 10.1021/acscatal.5b01792

A series of Grubbs–Hoveyda type catalyst precursors for olefin metathesis containing a maleimide moiety in the backbone of the NHC ligand was covalently incorporated in the cavity of the β-barrel protein nitrobindin. By using two protein mutants with different cavity sizes and choosing the suitable spacer length, an artificial metalloenzyme for olefin metathesis reactions in water in the absence of any organic cosolvents was obtained. High efficiencies reaching TON > 9000 in the ROMP of a water-soluble 7-oxanorbornene derivative and TON > 100 in ring-closing metathesis (RCM) of 4,4-bis(hydroxymethyl)-1,6-heptadiene in water under relatively mild conditions (pH 6, T = 25–40 °C) were observed.


Metal: Ru
Ligand type: Carbene
Host protein: Nitrobindin (Nb)
Anchoring strategy: Covalent
Optimization: Chemical
Reaction: Olefin metathesis
Max TON: 9900
ee: ---
PDB: ---
Notes: ROMP (cis/trans: 48/52)

Metal: Ru
Ligand type: Carbene
Host protein: Nitrobindin (Nb)
Anchoring strategy: Covalent
Optimization: Chemical
Reaction: Olefin metathesis
Max TON: 100
ee: ---
PDB: ---
Notes: RCM

A Rhodium Complex-Linked β-Barrel Protein as a Hybrid Biocatalyst for Phenylacetylene Polymerization

Hayashi, T

Chem. Commun. 2012, 48, 9756, 10.1039/C2CC35165J

Our group recently prepared a hybrid catalyst containing a rhodium complex, Rh(Cp)(cod), with a maleimide moiety at the peripheral position of the Cp ligand. This compound was then inserted into a β-barrel protein scaffold of a mutant of aponitrobindin (Q96C) via a covalent linkage. The hybrid protein is found to act as a polymerization catalyst and preferentially yields trans-poly(phenylacetylene) (PPA), although the rhodium complex without the protein scaffold normally produces cis PPA.


Metal: Rh
Ligand type: COD; Cp*
Host protein: Nitrobindin (Nb)
Anchoring strategy: Cystein-maleimide
Optimization: ---
Max TON: ---
ee: ---
PDB: ---
Notes: ---

Construction of a Hybrid Biocatalyst Containing a Covalently-Linked Terpyridine Metal Complex within a Cavity of Aponitrobindin

Onoda, A.

J. Inorg. Biochem. 2016, 158, 55-61, 10.1016/j.jinorgbio.2015.12.026

A hybrid biocatalyst containing a metal terpyridine (tpy) complex within a rigid β-barrel protein nitrobindin (NB) is constructed. A tpy ligand with a maleimide group, N-[2-([2,2′:6′,2′′-terpyridin]-4′-yloxy)ethyl]maleimide (1), was covalently linked to Cys96 inside the cavity of NB to prepare a conjugate NB–1. Binding of Cu2 +, Zn2 +, or Co2 + ion to the tpy ligand in NB–1 was confirmed by UV–vis spectroscopy and ESI–TOF MS measurements. Cu2 +-bound NB–1 is found to catalyze a Diels–Alder reaction between azachalcone and cyclopentadiene in 22% yield, which is higher than that of the Cu2 +–tpy complex without the NB matrix. The results suggest that the hydrophobic cavity close to the copper active site within the NB scaffold supports the binding of the two substrates, dienophile and diene, to promote the reaction.


Metal: Cu
Ligand type: Terpyridine
Host protein: Nitrobindin (Nb)
Anchoring strategy: Cystein-maleimide
Optimization: ---
Max TON: ---
ee: ---
PDB: ---
Notes: ---

Manganese Terpyridine Artificial Metalloenzymes for Benzylic Oxygenation and Olefin Epoxidation

Lewis, J.C.

Tetrahedron 2014, 70, 4245-4249, 10.1016/j.tet.2014.03.008

New catalysts for non-directed hydrocarbon functionalization have great potential in organic synthesis. We hypothesized that incorporating a Mn-terpyridine cofactor into a protein scaffold would lead to artificial metalloenzymes (ArMs) in which the selectivity of the Mn cofactor could be controlled by the protein scaffold. We designed and synthesized a maleimide-substituted Mn-terpyridine cofactor and demonstrated that this cofactor could be incorporated into two different scaffold proteins to generate the desired ArMs. The structure and reactivity of one of these ArMs was explored, and the broad oxygenation capability of the Mn-terpyridine catalyst was maintained, providing a robust platform for optimization of ArMs for selective hydrocarbon functionalization.


Metal: Mn
Ligand type: Poly-pyridine
Host protein: Nitrobindin (Nb)
Anchoring strategy: Covalent
Optimization: Chemical
Max TON: 19.2
ee: ---
PDB: 3EMM
Notes: ---

Metal: Mn
Ligand type: Poly-pyridine
Host protein: Nitrobindin (Nb)
Anchoring strategy: Covalent
Optimization: Chemical
Reaction: Epoxidation
Max TON: 19.8
ee: ---
PDB: 3EMM
Notes: ---

Photoinduced Hydrogen Evolution Catalyzed by a Synthetic Diiron Dithiolate Complex Embedded within a Protein Matrix

Onoda, A.

ACS Catal. 2014, 4, 2645-2648, 10.1021/cs500392e

The hydrogen-evolving diiron complex, (μ-S)2Fe2(CO)6 with a tethered maleimide moiety was synthesized and covalently embedded within the cavity of a rigid β-barrel protein matrix by coupling a maleimide moiety to a cysteine residue within the β-barrel. The (μ-S)2Fe2(CO)6 core within the cavity was characterized by UV–vis absorption and a characteristic CO vibration determined by IR measurements. The diiron complex embedded within the cavity retains the necessary catalytic activity (TON up to 130 for 6 h) to evolve H2 via a photocatalytic cycle with a Ru photosensitizer in a solution of 100 mM ascorbate and 50 mM Tris/HCl at pH 4.0 and 25 °C.


Metal: Fe
Ligand type: Carbonyl; Dithiolate
Host protein: Nitrobindin (Nb)
Anchoring strategy: Covalent
Optimization: ---
Reaction: H2 evolution
Max TON: 130
ee: ---
PDB: ---
Notes: ---

Rhodium-Complex-Linked Hybrid Biocatalyst: Stereo-Controlled Phenylacetylene Polymerization within an Engineered Protein Cavity

ChemCatChem 2014, n/a-n/a, 10.1002/cctc.201301055

The incorporation of a Rh complex with a maleimide moiety into the cavity of the nitrobindin β‐barrel scaffold by a covalent linkage at the 96‐position (Cys) provides a hybrid biocatalyst that promotes the polymerization of phenylacetylene. The appropriate structural optimization of the cavity by mutagenesis enhances the stereoselectivity of the polymer with a trans content of 82 % at 25 °C and pH 8.0. The X‐ray crystal structure of one of the hybrid biocatalysts at a resolution of 2.0 Å reveals that the Rh complex is located in the β‐barrel cavity without any perturbation to the total protein structure. Crystal structure analysis and molecular modeling support the fact that the stereoselectivity is enhanced by the effective control of monomer access to the Rh complex within the limited space of the protein cavity.


Metal: Rh
Ligand type: COD; Cp*
Host protein: Nitrobindin (Nb)
Anchoring strategy: Cystein-maleimide
Optimization: Genetic
Max TON: ---
ee: ---
PDB: 3WJC
Notes: ---