Productivity of Selective Electroenzymatic Reduction and Oxidation Reactions: Theoretical and Practical Considerations

Ruinatscha, Reto; Höllrigl, Volker; Otto, Katja; Schmid, Andreas

doi:10.1002/adsc.200600257

Cited by 37 publications

(16 citation statements)

References 55 publications

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“…They claim that among the reaction parameters, the productivity is the foremost issue to be improved. [15] Seen in this light, improving the catalytic properties of the established rhodium mediator should be a major goal for advancing NADPH-dependent electroenzymatic reactions. Screening a library of 12 new rhodium complexes, we identified those with adequate reduction potentials and catalytic activity.…”

Section: Discussionmentioning

confidence: 99%

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Synthesis, Characterization and Application of New Rhodium Complexes for Indirect Electrochemical Cofactor Regeneration

et al. 2008

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Electroenzymatic synthesis often suffers from electrochemical reaction steps which proceed slower than the coupled enzyme reaction. For indirect electrochemical cofactor regeneration, we here report two new mediators with superior properties compared to the established rhodium complex (2,2'-bipyridyl)(pentamethylcyclopentadienyl)rhodium [Cp*Rh(2,2'-bipyridine)]. After constructing a robotic system for fast and reliable cyclic voltammetry measurements, we screened twelve rhodium complexes with substituted 2,2'-bipyridine ligands for their reduction potentials and catalytic activity towards the reduction of NADP. Promising complexes were investigated in more detail by cyclic voltammetry and under batch electrolysis conditions. The new complexes Cp*Rh(5,5'-methyl-2,2'-bipyridine) and Cp*Rh(4,4'-methoxy-2,2'-bipyridine) reduced NADP to NADPH three times faster than the established mediator, resulting in volumetric productivities of up to 136 mmol L À1 d À1 and turnover frequencies of up to 113 h À1. This increased reaction rate of these new mediators makes indirect electrochemical approach significantly more competitive to other methods of cofactor regeneration.Abbreviations: ADH = alcohol dehydrogenase; Ag j AgCl = silver j silver chloride reference electrode; bpy = 2,2'-bipyridine; ci = current increase; Cp* = pentamethylcyclopentadienyl; CV = cyclic voltammetry; Ep = peak potential; equiv = equivalent; NADP/ NADPH = nicotinamide adenine dinucleotide phosphate oxidised/reduced form.

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Section: Discussionmentioning

confidence: 99%

“…[14,15] Overcoming this bottleneck by optimising the mediator should result in a faster overall reaction, making the indirect electrochemical cofactor regeneration more competitive and attractive for future applications.…”

Section: Full Papersmentioning

confidence: 99%

Synthesis, Characterization and Application of New Rhodium Complexes for Indirect Electrochemical Cofactor Regeneration

et al. 2008

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“…Most of the so far developed electroenzymatic processes display insufficient reaction stabilities and too low electrochemical cofactor regeneration rates with respect to the redox enzyme used as catalyst. [16] The driving force for high electrochemical cofactor regeneration rates is the mass transfer from the bulk solution to the depleted region near the electrode. As redox enzymes typically require very low cofactor concentrations in the micromolar to millimolar range, high cofactor amounts adjacent to electrode surfaces can only be sustained by increasing both cofactor transport rates from the bulk solution to the nearelectrode volume and high volumetric electrode surface areas for increasing the volume of the near-electrode layer.…”

Section: Introductionmentioning

confidence: 99%

“…[16,26] Since mixing needs to be carried out by a stirrer, these reactor systems are generally characterized by low electrode surface areas per reaction volume, as well as impaired mass transport from the stirred bulk solution to distant electrode surfaces. Volumetric cofactor regeneration rates are thus very likely to be limiting the enzymatic synthesis reaction.…”

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confidence: 99%

Productive Asymmetric Styrene Epoxidation Based on a Next Generation Electroenzymatic Methodology

Ruinatscha¹,

Dusny²,

Buehler³

et al. 2009

Adv Synth Catal

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Abstract:We have established a novel and scalable methodology for the productive coupling of redox enzymes to reductive electrochemical cofactor regeneration relying on efficient mass transfer of the cofactor to the electron-delivering cathode. Proof of concept is provided by styrene monooxygenase (StyA) catalyzing the asymmetric (S)-epoxidation of styrene with high enantiomeric excess, space-time yields, and current efficiencies. Highly porous reticulated vitreous carbon electrodes, maximized in volumetric surface area, were employed in a flowthrough mode to rapidly regenerate the consumed FADH 2 cofactor required for StyA activity. A systematic investigation of the parameters determining cofactor mass transfer revealed that low FAD concentrations and high flow rates enabled the continuous synthesis of the product (S)-styrene oxide at high rates, while at the same time the accumulation of the side-products acetophenone and phenylacetaldehyde was minimized. At 10 mm FAD and a flow rate of 150 mL min À1, an average space-time yield of 0.35 g L À1 h À1 could be achieved during 2 h with a final (S)-styrene oxide yield of 75.2%. At two-fold lower aeration rates, the electroenzymatic reaction could be sustained for 12 h, albeit at the expense of lower (59%) overall space-time yields. Under these conditions, as much as 20.5% of the utilized current could be channeled into (S)-styrene oxide formation. In comparison with state-of-the-art electroenzymatic methodologies for the same conversion, (S)-styrene oxide synthesis could be improved up to 150-fold with respect to both reaction time and space-time yield. These productivities constitute the most efficient reaction reported for asymmetric in vitro epoxidations of styrene.

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“…This became evident in a recent survey by Ruinatscha et al, in which electroenzymatic processes were evaluated with regard to their application potential. [6] Out of thirteen reviewed reactions, only three showed sufficient process performance to be of industrial relevance, while the others displayed insufficient productivity or process stability.…”

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confidence: 98%

Electroenzymatic Asymmetric Reduction of rac‐3‐Methylcyclohexanone to (1S,3S)‐3‐Methylcyclohexanol in Organic/Aqueous Media Catalyzed by a Thermophilic Alcohol Dehydrogenase

2007

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Electrochemical regeneration of nicotinamide cofactors has been discussed as a promising, clean, and sustainable technology since the 1980s. However, most concepts for the coupling of this technology to enzymes suffer from low productivities, insufficient stabilities, or are difficult to scale up. We have developed an electrochemical cell for the efficient regeneration of NAD(P)H, which can be coupled to a reduction reaction catalyzed by the thermophilic alcohol dehydrogenase from Thermus sp. Octane, as second organic phase avoided product inhibition and allowed for the production of (1S,3S)-3-methylcyclohexanol at a diastereomeric excess of 96 % from the corresponding racemic ketone with a productivity of 0.13 g L À1 h À1 and a current efficiency of 85 %. After 10 h, the experiment was actively terminated and the final product concentration reached was 1.32 g L À1. In our opinion this concept defines a new state of the art in electroenzymology and provides a strong basis for applications in organic synthesis.

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Productivity of Selective Electroenzymatic Reduction and Oxidation Reactions: Theoretical and Practical Considerations

Cited by 37 publications

References 55 publications

Synthesis, Characterization and Application of New Rhodium Complexes for Indirect Electrochemical Cofactor Regeneration

Synthesis, Characterization and Application of New Rhodium Complexes for Indirect Electrochemical Cofactor Regeneration

Productive Asymmetric Styrene Epoxidation Based on a Next Generation Electroenzymatic Methodology

Electroenzymatic Asymmetric Reduction of rac‐3‐Methylcyclohexanone to (1S,3S)‐3‐Methylcyclohexanol in Organic/Aqueous Media Catalyzed by a Thermophilic Alcohol Dehydrogenase

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