Bioinspired design of a hybrid bifunctional enzymatic/organic electrocatalyst for site selective alcohol oxidation

Abstract

This work combines the thermostable alcohol dehydrogenase D (AdhD) from Pyrococcus furiosus and the organic electrocatalyst TEMPO to create a bifunctional catalyst that selectively oxidizes primary and secondary alcohols. The active sites function independently, can be switched on by changing reaction conditions, and can selectively oxidize a mixture of 1- and 2-butanol. The NAD-dependent enzyme catalyses the secondary alcohol oxidation at a rate 3-fold faster than the primary alcohol, while the covalently attached 4-glycidyl-TEMPO oxidizes 1-butanol and has negligible activity toward 2-butanol. This hybrid catalytic approach has potential value for selective alcohol oxidations as well as other electrochemical and enzymatic multistep processes in energy conversion and chemical synthesis.

Selective Electrochemical Oxidation of Alcohols Catalyzed by Partially Biobased TEMPO Analogs**

“…Some very good literature reports on the selectivity in this type of system are available. For example, lignin and lignin models have been selectively oxidized by a TEMPO derivative at the β-O-4 linkages in work by multiple groups [37][38] In other work, a bifunctional TEMPO catalyst that also selectively oxidizes alcohols was reported [39] in addition to an earlier report of computational model. [40] The general mechanism of alcohol oxidation by TEMPO is affected by many factors including the stability of the oxoammonium cations and the oxidation potentials.…”

Electrochemical Activation of Galactose Oxidase: Mechanistic Studies and Synthetic Applications

“…Electrochemistry is a green and sustainable technology that has been widely applied in bioanalysis, synthetic chemistry, and energy interconversion. Merging biocatalysis with alternative catalytic techniques such as electrocatalysis or photocatalysis further expands the scope of biocatalytic synthesis by accessing higher reactivity and selectivity or unlocking novel enzymatic cascades or un-natural reactivities. − In many examples of bioelectrocatalytic reactions, terminal oxidants or reductants have been demonstrated to be completely replaceable with electricity, offering enormous potential in the efficient manufacture of pharmaceuticals and fine chemicals. , Herein, we disclose the development of the first bioelectrocatalytic aerobic oxidation of alcohols via electrochemical activation of GOase. , We have successfully applied this new synthetic reaction to desymmetrizing oxidation of 2-ethynylglycerol, a key step in biocatalytic cascade synthesis of islatravir, and expanded the synthetic scope to a range of alcohols. Spectroscopic and electrochemical studies have revealed the redox properties of the specifically engineered GALO-104 (GOase Rd10BB in ref ) as well as the proton-coupled electron-transfer (PCET) mechanism of GOase oxidation by the mediator.…”

“…15,16 Herein, we disclose the development of the first bioelectrocatalytic aerobic oxidation of alcohols via electrochemical activation of GOase. 17,18 We have successfully applied this new synthetic reaction to desymmetrizing oxidation of 2-ethynylglycerol, a key step in biocatalytic cascade synthesis of islatravir, and expanded the synthetic scope to a range of alcohols. Spectroscopic and electrochemical studies have revealed the redox properties of the specifically engineered GALO-104 (GOase Rd10BB in ref 3) 19 as well as the proton-…”

Electron-Rich Phenoxyl Mediators Improve Thermodynamic Performance of Electrocatalytic Alcohol Oxidation with an Iridium Pincer Complex

“…The use of mediators in electrochemical reactions has a long history in electrosynthesis, − including bioinspired mediators such as quinones − and NAD+, as well as nitroxyls . Nitroxyls can function both as alcohol oxidation electrocatalysts − and mediators that operate by hydrogen atom abstraction (e.g., Cu-coordinated alcohols). ,− Ferrocene, flavins, and polypyridyl complexes of ruthenium and osmium mediate the transfer of electrons from glucose oxidases to anodes in glucose-detection technologies and fuel cells. ,, Typically, mediators are two-electron/two-proton shuttles or agents that mediate electron transfer.…”