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Unspecific Peroxygenases (UPOs) have emerged as robust biocatalysts for selective oxygenation reactions, as they are easily produced at scale and require only hydrogen peroxide as the external oxidant. UPOs can catalyze the oxygenation of the primary benzylic carbons of toluenes to give alcohol, aldehyde and carboxylic acid products. They can also catalyze hydroxylation at the benzylic position of ethylbenzenes, and the subsequent oxidation of the secondary alcohols to ketones. In this study, we have investigated factors that affect the balance of products in UPO‐catalyzed benzylic oxygenations using a range of functionalised toluenes and ethyl benzenes, and a UPO from Agrocybe aegerita (rAaeUPO‐PaDa‐I‐H variant). The product distribution is dependent upon a mixture of steric and electronic effects and, in selected cases, controlling the reaction conditions permits products from each product series to be generated chemoselectively. In this way, electron poor toluenes were converted directly into carboxylic acids in isolated yields of 36–99 % on preparative scale. [ABSTRACT FROM AUTHOR]

Unspecific Peroxygenases (UPOs) are increasingly significant enzymes for selective oxygenations as they are stable, highly active and catalyze their reactions at the expense of only hydrogen peroxide as the oxidant. Their structural similarity to chloroperoxidase (CPO) means that UPOs can also catalyze halogenation reactions based upon the generation of hypohalous acids from halide and H2O2. Here we show that the halogenation and oxygenation modes of a UPO can be stimulated at different pH values. Using simple aromatic compounds such as thymol, we show that, at a pH of 3.0 and 6.0, either brominated or oxygenated products respectively are produced. Preparative 100 mg scale transformations of substrates were performed with 60–72 % isolated yields of brominated products obtained. A one‐pot bromination‐oxygenation cascade reaction on 4‐ethylanisole, in which the pH was adjusted from 3.0 to 6.0 at the halfway stage, yielded sequentially brominated and oxygenated products 1‐(3‐bromo‐4‐methoxyphenyl)ethyl alcohol and 3‐bromo‐4‐methoxy acetophenone with 82 % combined conversion. These results identify UPOs as an unusual example of a biocatalyst that is tunable for entirely different chemical reactions, dependent upon the reaction conditions. [ABSTRACT FROM AUTHOR]

A lyophilized preparation of an unspecific peroxygenase variant from Agrocybe aegerita (rAaeUPO‐PaDa‐I‐H) is a highly effective catalyst for the oxygenation of a diverse range of N‐heterocyclic compounds. Scalable biocatalytic oxygenations (27 preparative examples, ca. 100 mg scale) have been developed across a wide range of substrates, including alkyl pyridines, bicyclic N‐heterocycles and indoles. H2O2 is the only stoichiometric oxidant needed, without auxiliary electron transport proteins, which is key to the practicality of the method. Reaction outcomes can be altered depending on whether hydrogen peroxide was delivered by syringe pump or through in situ generation using an alcohol oxidase from Pichia pastoris (PpAOX) and methanol as a co‐substrate. Good synthetic yields (up to 84 %), regioselectivity and enantioselectivity (up to 99 % ee) were observed in some cases, highlighting the promise of UPOs as practical, versatile and scalable oxygenation biocatalysts. [ABSTRACT FROM AUTHOR]

Having identified inconsistencies when repeating literature examples of photochemical transformations and difficulties recreating experimental setups, we devised several criteria that an ideal lab‐scale reactor should achieve. Herein, we introduce a versatile photoreactor for high‐throughput screening, preparative‐scale batch reactions and continuous processing, all with a single light source. The reactor utilizes interchangeable arrays of pseudo‐monochromatic high‐power LEDs in a range of synthetically useful wavelengths, combined with excellent temperature control. Moreover, light intensity can be modulated in an accurate and straightforward manner. This system has subsequently been tested on a range of literature methodologies. [ABSTRACT FROM AUTHOR]

Photoreactive and thermoresponsive N-isopropylacrylamide (NIPAM)-surfmer copolymer hydrogels containing 4,4′-di(6-sulfato-hexyloxy)azobenzene (DSHA) dianions are described. The functional hydrogels are obtained in a two steps. First a micellar aqueous solution of (11-(acryloyloxy)undecyl)trimethylammonium bromide (AUTMAB) and NIPAM is exposed to 60Co-gamma irradiation, and a thermoresponsive copolymer gel is obtained. Second, DSHA is included by shrinking the gel at 50 °C and subsequent reswelling in an aqueous solution of DSHA disodium salt at 20 °C. Reswelling is accompanied by electrostatic adsorption of DSHA dianions at the positively charged AUTMAB headgroups replacing the bromide ions. Gels containing trans-DSHA are transparent yellow at room temperature ( λmax = 370 nm), while gels containing cis-rich DSHA are orange ( λmax = 460 and 330 nm). Energy dispersive X-ray measurements indicate that 41% of the bromide ions are exchanged if trans-DSHA is used for adsorption, and only 7.5% if cis-DSHA is used. The incorporation of DSHA lowers the lower critical solution temperature (LCST) from 34 to 32 °C. Below the LCST, DSHA can be switched from the trans- to the cis-rich state and vice versa upon irradiation with UV ( λ = 366 nm) or visible light ( λ ≥ 450 nm). Above the LCST no photoreaction takes place. [ABSTRACT FROM AUTHOR]

Controlling the selectivity of a chemical reaction with external stimuli is common in thermal processes, but rare in visible-light photocatalysis. Here we show that the redox potential of a carbon nitride photocatalyst (CN-OA-m) can be tuned by changing the irradiation wavelength to generate electron holes with different oxidation potentials. This tuning was the key to realizing photo-chemo-enzymatic cascades that give either the (S)- or the (R)-enantiomer of phenylethanol. In combination with an unspecific peroxygenase from Agrocybe aegerita, green light irradiation of CN-OA-m led to the enantioselective hydroxylation of ethylbenzene to (R)-1-phenylethanol (99 % ee). In contrast, blue light irradiation triggered the photocatalytic oxidation of ethylbenzene to acetophenone, which in turn was enantioselectively reduced with an alcohol dehydrogenase from Rhodococcus ruber to form (S)-1-phenylethanol (93 % ee)., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)