Aqueous Phase Transfer Hydrogenation of Aryl Ketones Catalysed by Achiral Ruthenium(II) and Rhodium(III) Complexes and their Papain Conjugates
Appl. Organomet. Chem. 2013, 27, 6-12, 10.1002/aoc.2929
Several ruthenium and rhodium complexes including 2,2′‐dipyridylamine ligands substituted at the central N atom by an alkyl chain terminated by a maleimide functional group were tested along with a newly synthesized Rh(III) complex of unsubstituted 2,2′‐dipyridylamine as catalysts in the transfer hydrogenation of aryl ketones in neat water with formate as hydrogen donor. All of them except one led to the secondary alcohol products with conversion rates depending on the metal complex. Site‐specific anchoring of the N‐maleimide complexes to the single free cysteine residue of the cysteine endoproteinase papain endowed this protein with transfer hydrogenase properties towards 2,2,2‐trifluoroacetophenone. Quantitative conversions were reached with the Rh‐based biocatalysts, while modest enantioselectivities were obtained in certain reactional conditions.
Ligand type: Cp*; Poly-pyridineMax TON: 96ee: 15PDB: ---Notes: ---
Autoxidation of Ascorbic Acid Catalyzed by a Semisynthetic Enzyme
Biopolymers 1990, 29, 39-43, 10.1002/bip.360290107
The semisyntehtic enzyme 6 was prepared by alkylation of the cysteine‐25 sulfhydryl group of papain with the bipyridine 5 and was shown to stoichiometrically bind copper ion; 7 catalyzed the autoxidation of ascorbic acid derivatives with saturation kinetics approximately 20‐fold faster than a model system using 3‐Cu(II).
Metal: CuLigand type: BipyridineOptimization: ---Reaction: OxidationMax TON: ---ee: ---PDB: ---Notes: ---
Chemically Engineered Papain as Artificial Formate Dehydrogenase for NAD(P)H Regeneration
Org. Biomol. Chem. 2011, 9, 5720, 10.1039/c1ob05482a
Organometallic complexes of the general formula [(η6-arene)Ru(N⁁N)Cl]+ and [(η5-Cp*)Rh(N⁁N)Cl]+ where N⁁N is a 2,2′-dipyridylamine (DPA) derivative carrying a thiol-targeted maleimide group, 2,2′-bispyridyl (bpy), 1,10-phenanthroline (phen) or ethylenediamine (en) and arene is benzene, 2-chloro-N-[2-(phenyl)ethyl]acetamide or p-cymene were identified as catalysts for the stereoselective reduction of the enzyme cofactors NAD(P)+ into NAD(P)H with formate as a hydride donor. A thorough comparison of their effectiveness towards NAD+ (expressed as TOF) revealed that the RhIII complexes were much more potent catalysts than the RuII complexes. Within the RuII complex series, both the N⁁N and arene ligands forming the coordination sphere had a noticeable influence on the activity of the complexes. Covalent anchoring of the maleimide-functionalized RuII and RhIII complexes to the cysteine endoproteinase papain yielded hybrid metalloproteins, some of them displaying formate dehydrogenase activity with potentially interesting kinetic parameters.
Ligand type: Cp*; Poly-pyridineMax TON: ---ee: ---PDB: ---Notes: TOF = 52.1 h-1 for NAD+
Electrochemical Characterization of the Artificial Metalloenzyme Papain-[(η6-arene)Ru(1,10-phenanthroline)Cl]+
J. Electroanal. Chem. 2020, 859, 113882, 10.1016/j.jelechem.2020.113882
Electrochemical properties were studied for [(η6-arene)Ru(1,10-phenanthroline)Cl]Cl (arene = C6H5(CH2)2NHCOCH2Cl) organometallic complex 1, protein Papain PAP and its conjugate with organometallic complex 1-PAP. The latter can serve as an artificial metalloenzyme with catalytic activity in transfer hydrogenation. This work demonstrates that AC voltammetry and electrochemical impedance spectroscopy can be used as fast tools to screen the catalytic ability of 1-PAP electrochemically by studies of the catalytic hydrogen evolution reaction (HER). Proteins are known to catalyze this process, but we have shown that additional HER signal associated with the catalytic activity of 1 is observed for its conjugate with Papain 1-PAP.
Ligand type: Cp*; PhenanthrolineOptimization: ---Reaction: H2 evolutionMax TON: ---ee: ---PDB: ---Notes: ---
Merging Homogeneous Catalysis with Biocatalysis; Papain as Hydrogenation Catalyst
Chem. Commun. 2005, 5656, 10.1039/B512138H
Papain, modified at Cys-25 with a monodentate phosphite ligand and complexed with Rh(COD)2BF4, is an active catalyst in the hydrogenation of methyl 2-acetamidoacrylate.
Ligand type: PhosphineOptimization: ---Max TON: 400ee: <10PDB: ---Notes: ---
Metal-Conjugated Affinity Labels: A New Concept to Create Enantioselective Artificial Metalloenzymes
ChemistryOpen 2013, 2, 50-54, 10.1002/open.201200044
How to train a protein: Metal‐conjugated affinity labels were used to selectively position catalytically active metal centers in the binding pocket of proteases. The resulting artificial metalloenzymes achieve up to 82 % e.r. in the hydrogenation of ketones. The modular setup enables a rapid generation of artificial metalloenzyme libraries, which can be adapted to a broad range of catalytic conditions.
Max TON: 89ee: 64PDB: ---Notes: ---
Piano-Stool d(6)-Rhodium(III) Complexes of Chelating Pyridine-Based Ligands and their Papain Bioconjugates for the Catalysis of Transfer Hydrogenation of Aryl Ketones in Aqueous Medium
J. Mol. Catal. B: Enzym. 2015, 122, 314-322, 10.1016/j.molcatb.2015.10.007
Two half-sandwich d6-rhodium(III) complexes of the general formula [(η5-Cp*)Rh(N^N)Cl]Cl where N^N is a phenanthroline or a bispyridine methane derivative carrying a thiol-targeting maleimide or chloroacetamide function were synthesized and characterized. Both complexes were able to catalyse the transfer hydrogenation of 2,2,2-trifluoroacetophenone in aqueous medium using formate or phosphite as hydrogen donor. Covalent anchoring of these complexes to the cysteine endoproteinase papain yielded hybrid metalloproteins with transfer hydrogenase properties. Under optimized conditions of pH, hydrogen donor concentration and catalyst load, conversion of substrate was nearly quantitative within 24 h at 40 °C and the (S)-enantiomer was obtained preferably albeit with a modest enantiomeric excess of 7–10%. Covalent docking simulations complemented the experimental findings suggesting a molecular rationale for the observed low enantioselectivity. The harmonious use of experimental and theoretical approaches represents an unprecedented starting point for driving the rational design of artificial metalloenzymes built up from papain with higher catalytic efficiency.
Ligand type: Cp*; PhenanthrolineReaction: Transfer hydrogenationMax TON: 30ee: 9PDB: ---Notes: ---
Ligand type: Cp*; Di(2-pyridyl)Reaction: Transfer hydrogenationMax TON: 20ee: 5PDB: ---Notes: ---
Towards the Directed Evolution of Hybrid Catalysts
Chimia 2002, 56, 721-723, 10.2533/000942902777679920
The first step in applying the recently proposed concept concerning the application of directed evolution to the creation of selective hybrid catalysts is described, specifically the covalent attachment of Mn-salen moieties and of Cu-, Pd-, and Rh-complexes of dipyridine derivatives as well as the implantation of a diphosphine moiety in a protein, future steps being cycles of mutagenesis/screening.
Metal: MnLigand type: SalenOptimization: ---Reaction: EpoxidationMax TON: ---ee: < 10PDB: ---Notes: ---
Ligand type: Dipyridin-2-ylmethaneOptimization: ---Max TON: ---ee: < 10PDB: ---Notes: ---
(η6-Arene) Ruthenium(II) Complexes and Metallo-Papain Hybrid as Lewis Acid Catalysts of Diels–Alder Reaction in Water
Dalton Trans. 2010, 39, 5605, 10.1039/c001630f
Covalent embedding of a (η6-arene) ruthenium(II) complex into the protein papain gives rise to a metalloenzyme displaying a catalytic efficiency for a Lewis acid-mediated catalysed Diels–Alder reaction enhanced by two orders of magnitude in water.
Ligand type: Benzene; PhenanthrolineReaction: Diels-Alder reactionMax TON: 440ee: ---PDB: ---Notes: TOF = 220 h-1