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A copper(II) cofactor coupled to a testosterone anchor, copper(II)-(5-(Piperazin-1-yl)-1,10-phenanthroline)testosterone-17-hemisuccinamide (10) was synthesized and associated with a neocarzinostatin variant, NCS-3.24 (KD =3 μm), thus generating a new artificial metalloenzyme by following a "Trojan horse" strategy. Interestingly, the artificial enzyme was able to efficiently catalyze the Diels-Alder cyclization reaction of cyclopentadiene (1) with 2-azachalcone (2). In comparison with what was observed with cofactor 10 alone, the artificial enzymes favored formation of the exo products (endo/exo ratios of 84:16 and 62:38, respectively, after 12 h). Molecular modeling studies assigned the synergy between the copper complex and the testosterone (KD =13 μm) moieties in the binding of 10 to good van der Waals complementarity. Moreover, by pushing the modeling exercise to its limits, we hypothesize on the molecular grounds that are responsible for the observed selectivity., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A new biocatalyst MP8@MIL‐101(Cr/Fe) was prepared by immobilization of a heme octapeptide, Microperoxidase 8 (MP8) within a mixed metal MOF, MIL‐101(Cr/Fe). Both MIL‐101(Cr/Fe) and MP8@MIL‐101(Cr/Fe) were characterized by PXRD, FTIR spectroscopy and TGA. The catalytic activity of MP8@MIL‐101(Cr/Fe) for the oxidation of styrene by H2O2 and tBuOOH was then examined under various reaction conditions (nature of the co‐solvent and of the oxidant, concentration of the oxidant and of the substrate, time, pH) and compared to that of MP8 alone. Under the best conditions used, MP8@MIL‐101(Cr/Fe) was then shown to catalyze the oxidation of styrene about 3 times more efficiently than MP8 alone with approximately 50 % selectivity for styrene oxide. [ABSTRACT FROM AUTHOR]

Microperoxidase‐8, a small, peroxidase‐type enzyme was immobilized into nanoparticles of the mesoporous and ultra‐stable metal–organic framework (MOF) MIL‐101(Cr). The immobilized enzyme fully retained its catalytic activity and exhibited enhanced resistance to acidic conditions. The biocatalyst was reusable and showed a long‐term stability. By exploiting the properties of the MOF′s framework, we demonstrated, for the first time, that the MOF matrix could act in synergy with the enzyme (Microperoxidase‐8) and enhance selectivity the oxidation reaction of dyes. The oxidation rate of the harmful negatively charged dye (methyl orange) was significantly increased after enzyme immobilization, probably as a result of the pre‐concentration of the methyl orange reactant owing to a charge matching between this dye and the MOF. Fatal attraction: The enzyme microperoxidase‐8 was immobilized into nanoparticles of the mesoporous and ultra‐stable metal–organic framework (MOF) MIL‐101(Cr) resulting in enhanced resistance to acidic media. The oxidation rate of the harmful negatively charged methyl orange, which is attracted to the MOF, was significantly increased after enzyme immobilization. [ABSTRACT FROM AUTHOR]

Abstract: Catalytic antibodies with a metalloporphyrin cofactor or “hemoabzymes”, used as models for hemoproteins like peroxidases and cytochrome P450s, represent a promising route to catalysts tailored for selective oxidation reactions. The first strategy has been to produce anti-porphyrin antibodies, raised against various N-substituted- and meso-carboxyaryl-porphyrins, which led to monoclonal antibodies exhibiting, in the presence of the corresponding iron-porphyrin cofactor, a significant peroxidase activity. We ourselves obtained an artificial hemoprotein by associating a monoclonal antibody, 13G10, and its iron(III)-α,α,α,β-meso-tetrakis(ortho-carboxyphenyl)porphyrin (Fe(ToCPP)) hapten, which exhibited a significant peroxidase activity. Biological studies suggested that in this antibody, a carboxylic acid side chain of the protein participated in the catalysis, but no amino acid residue acting as an axial ligand of the iron was detected. Therefore, to provide the iron atom with an axial ligand, we raised antibodies against microperoxidase 8, a heme octapeptide containing a histidine bound to the iron atom. This strategy was successful, as an antibody–microperoxidase 8 complex (3A3–MP8) led to the best k cat/K m ever reported for antibody–porphyrin complexes. The ability of the 3A3–MP8 complex to catalyze the selective oxidation of substrates was studied and it was found able to catalyze the regioselective nitration of aromatics by NO2 −/H2O2 as well as the stereoselective oxidation of sulfides like thioanisole by H2O2. Other strategies based on antibodies have to be developed to obtain more efficient biomimetic systems for cytochrome P450s. A first one could involve the modification of anti-substrate antibodies by covalent linkage of an iron(III)-porphyrin close to the binding site of the substrate, to obtain an artificial hemoprotein able to catalyze its regioselective oxidation. [Copyright &y& Elsevier]

A new zinc(II)-cofactor coupled to a testosterone anchor, zinc(II)- N , N -bis(2-pyridylmethyl)-1,3-diamino-propa-2-ol- N ′(17′-succinimidyltestosterone) (Zn-Testo-BisPyPol) 1 -Zn has been synthesized and fully characterized. It has been further associated with a neocarzinostatin variant, NCS-3.24, to generate a new artificial metalloenzyme following the so-called ‘Trojan horse’ strategy. This new 1 -Zn-NCS-3.24 biocatalyst showed an interesting catalytic activity as it was found able to catalyze the hydrolysis of the RNA model HPNP with a good catalytic efficiency ( k cat / K M = 13.6 M −1 s −1 at pH 7) that places it among the best artificial catalysts for this reaction. Molecular modeling studies showed that a synergy between the binding of the steroid moiety and that of the BisPyPol into the protein binding site can explain the experimental results, indicating a better affinity of 1 -Zn for the NCS-3.24 variant than testosterone and testosterone-hemisuccinate themselves. They also show that the artificial cofactor entirely fills the cavity, the testosterone part of 1 -Zn being bound to one the two subdomains of the protein providing with good complementarities whereas its metal ion remains widely exposed to the solvent which made it a valuable tool for the catalysis of hydrolysis reactions, such as that of HPNP. Some possible improvements in the ‘Trojan horse’ strategy for obtaining better catalysts of selective reactions will be further studied. [ABSTRACT FROM AUTHOR]