Salmain, M.

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.

Kaiser, E.T.

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).

Salmain, M.

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.

Ueno, T.

Small 2010, 6, 1873-1879, 10.1002/smll.201000772

The synthesis of a robust bio‐nanotube consisting of the β‐helical tubular component proteins of bacteriophage T4 is described. The crystal structure indicates that it has a well‐defined nanoscale length of 10 nm as a result of the head‐to‐head dimerization of β‐helices. Surprisingly, the tube assembly has high thermal stability, high tolerance to organic solvents, and a wide pH‐stability range.

Ueno, T.

Chem. Commun. 2011, 47, 2074, 10.1039/C0CC03015E

We have constructed a robust β-helical nanotube from the component proteins of bacteriophage T4 and modified this nanotube with RuII(bpy)3 and ReI(bpy)(CO)3Cl complexes. The photocatalytic system arranged on the tube catalyzes the reduction of CO2 with higher reactivity than that of the mixture of the monomeric forms.

Hromadová, M.

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.

de Vries, J.

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.

Eppinger, J.

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.

Mangiatordi, G.F.; Salmain, M.

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.

Ueno, T.

Dalton Trans. 2012, 41, 11424, 10.1039/C2DT31030A

We have succeeded in preparing semi-synthesized proteins bound to Sc3+ ion which can promote an epoxide ring-opening reaction. The Sc3+ binding site was created on the surface of [(gp5βf)3]2 (N. Yokoi et al., Small, 2010, 6, 1873) by introducing a cysteine residue for conjugation of a bpy moiety using a thiol–maleimide coupling reaction. Three cysteine mutants [(gp5βf_X)3]2 (X = G18C, L47C, N51C) were prepared to introduce a bpy in different positions because it had been reported that Sc3+ ion can serve as a Lewis-acid catalyst for an epoxide ring-opening reaction upon binding of epoxide to bpy and two –ROH groups. G18C_bpy with Sc3+ can accelerate the rate of catalysis of the epoxide ring-opening reaction and has the highest rate of conversion among the three mutants. The value is more than 20 times higher than that of the mixtures of [(gp5βf)3]2/2,2′-bipyridine and L-threonine/2,2′-bipyridine. The elevated activity was obtained by the cooperative effect of stabilizing the Sc3+ coordination and accumulation of substrates on the protein surface. Thus, we expect that the semi-synthetic approach can provide insights into new rational design of artificial metalloenzymes.

Reetz, M.T.

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.

Salmain, M.

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.