Marchetti, M.

Adv. Synth. Catal. 2002, 344, 556, 10.1002/1615-4169(200207)344:5<556::AID-ADSC556>3.0.CO;2-E

The water‐soluble complex derived from Rh(CO)2(acac) and human serum albumin (HSA) proved to be efficient in the hydroformylation of several olefin substrates. The chemoselectivity and regioselectivity were generally higher than those obtained by using the classic catalytic systems like TPPTS‐Rh(I) (TPPTS=triphenylphosphine‐3,3′,3″‐trisulfonic acid trisodium salt). Styrene and 1‐octene, for instance, were converted in almost quantitative yields into the corresponding oxo‐aldehydes at 60 °C and 70 atm (CO/H2=1) even at very low Rh(CO)2(acac)/HSA catalyst concentrations. The possibility of easily recovering the Rh(I) compound makes the system environmentally friendly. The circular dichroism technique was useful for demonstrating the Rh(I) binding to the protein and to give information on the stability in solution of the catalytic system. Some other proteins have been used to replace HSA as complexing agent for Rh(I). The results were less impressive than those obtained using HSA and their complexes with Rh(I) were much less stable.

Ward, T.R.

Org. Biomol. Chem. 2015, 13, 357-360, 10.1039/c4ob02071e

Stereoselectively labelled isotopomers of NAD(P)H are highly relevant for mechanistic studies of enzymes which utilize them as redox equivalents.

Bäckvall, J.E.; Diéguez, M.; Pàmies, O.

Adv. Synth. Catal. 2015, 357, 1567-1586, 10.1002/adsc.201500290

Artificial metalloenzymes combine the excellent selective recognition/binding properties of enzymes with transition metal catalysts, and therefore many asymmetric transformations can benefit from these entities. The search for new successful strategies in the construction of metal‐enzyme hybrid catalysts has therefore become a very active area of research. This review discusses all the developed strategies and the latest advances in the synthesis and application in asymmetric catalysis of artificial metalloenzymes with future directions for their design, synthesis and application (Sections 2–4). Finally, advice is presented (to the non‐specialist) on how to prepare and use artificial metalloenzymes (Section 5).

Harada, A.

Org. Biomol. Chem. 2006, 4, 3571, 10.1039/B609242J

Monoclonal antibodies have been elicited against an achiral rhodium complex and this complex was used in the presence of a resultant antibody, 1G8, for the catalytic hydrogenation of 2-acetamidoacrylic acid to produce N-acetyl-L-alanine in high (>98%) enantiomeric excess.

Ward, T.R.

Org. Biomol. Chem. 2015, 13, 5652-5655, 10.1039/c5ob00428d

We report an efficient artificial metathesase which combines an arylsulfonamide anchor within the protein scaffold human carbonic anhydrase 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.

Ward, T.R.

Org. Biomol. Chem. 2007, 5, 1835, 10.1039/b702068f

Artificial metalloenzymes based on biotin–streptavidin technology, a “fusion” of chemistry and biology, illustrate how asymmetric catalysts can be improved and evolved using chemogenetic approaches.

Okuda, J.

Org. Biomol. Chem. 2016, 14, 9174-9183, 10.1039/C6OB01475E

The incorporation of organometallic catalyst precursors in proteins results in so-called artificial metalloenzymes. The protein structure will control activity, selectivity and stability of the organometallic site in aqueous medium and allow non-natural reactions in biological settings. Grubbs-Hoveyda type ruthenium catalysts with an N-heterocyclic carbene (NHC) as ancillary ligand, known to be active in olefin metathesis, have recently been incorporated in various proteins. An overview of these artificial metalloproteins and their potential application in olefin metathesis is given.

Filice, M.; Palomo, J.M.

Adv. Synth. Catal. 2015, 357, 2687-2696, 10.1002/adsc.201500014

A p‐nitrophenylphosphonate palladium pincer was synthesized and selectively inserted by irreversible attachment on the catalytic serine of different commercial lipases with good to excellent yields in most cases. Among all, lipase from Candida antarctica B (CAL‐B) was the best modified enzyme. The artificial metalloenzyme CAL‐B‐palladium (Pd) catalyst was subsequently immobilized on different supports and by different orienting strategies. The catalytic properties of the immobilized hybrid catalysts were then evaluated in two sets of Heck cross‐coupling reactions under different conditions. In the first reaction between iodobenzene and ethyl acrylate, the covalent immobilized CAL‐B‐Pd catalyst resulted to be the best one exhibiting quantitative production of the Heck product at 70 °C in dimethylformamide (DMF) with 25% water and particularly in pure DMF, where the soluble Pd pincer was completely inactive. A post‐immobilization engineering of catalyst surface by its hydrophobization enhanced the activity. The selectivity properties of the best hybrid catalyst were then assessed in the asymmetric Heck cross‐coupling reaction between iodobenzene and 2,3‐dihydrofuran retrieving excellent results in terms of stereo‐ and enantioselectivity.

Ward, T.R.

Adv. Synth. Catal. 2007, 349, 1923-1930, 10.1002/adsc.200700022

We report on our efforts to create efficient artificial metalloenzymes for the enantioselective hydrogenation of N‐protected dehydroamino acids using either avidin or streptavidin as host proteins. Introduction of chiral amino acid spacers – phenylalanine or proline – between the biotin anchor and the flexible aminodiphosphine moiety 1, combined with saturation mutagenesis at position S112X of streptavidin, affords second generation artificial hydrogenases displaying improved organic solvent tolerance, reaction rates (3‐fold) and (S)‐selectivities (up to 95 % ee for N‐acetamidoalanine and N‐acetamidophenylalanine). It is shown that these artificial metalloenzymes follow Michaelis–Menten kinetics with an increased affinity for the substrate and a higher kcat than the protein‐free catalyst (compare kcat 3.06 min−1 and KM 7.38 mM for [Rh(COD)Biot‐1]+ with kcat 12.30 min−1 and KM 4.36 mM for [Rh(COD)Biot‐(R)‐Pro‐1]+ ⊂ WT Sav). Finally, we present a straightforward protocol using Biotin‐Sepharose to immobilize artificial metalloenzymes (>92 % ee for N‐acetamidoalanine and N‐acetamidophenylalanine using [Rh(COD)Biot‐(R)‐Pro‐1]+ ⊂ Sav S112W).

Mahy, J.-P.

Org. Biomol. Chem. 2009, 7, 3208, 10.1039/b907534h

Two new artificial hemoproteins or “hemozymes”, obtained by non covalent insertion of Fe(III)-meso-tetra-p-carboxy- and -p-sulfonato-phenylporphyrin into xylanase A from Streptomyces lividans, were characterized by UV-visible spectroscopy and molecular modeling studies, and were found to catalyze the chemo- and stereoselective oxidation of thioanisole into the S sulfoxide, the best yield (85 ± 4%) and enantiomeric excess (40% ± 3%) being obtained with Fe(III)-meso-tetra-p-carboxyphenylporphyrin-Xln10A as catalyst in the presence of imidazole as co-catalyst.