Piezobiocatalysis: Ultrasound-Driven Enzymatic Oxyfunctionalization of C–H Bonds

Abstract

Peroxygenases have long inspired the selective oxyfunctionalization of various aliphatic and aromatic compounds, because of their broad substrate spectrum and simplicity of catalytic mechanism. This study provides a proof-of-concept of piezobiocatalysis by demonstrating peroxygenase-catalyzed oxyfunctionalization reactions fueled by piezocatalytically generated H 2 O 2. Bismuth oxychloride (BiOCl) generated H 2 O 2 in situ via an oxygen reduction reaction under ultrasonic wave conditions. Through the simple combination of water, ultrasound, recombinant, evolved unspecific peroxygenase from Agrocybe aegerita (rAaeUPO), and BiOCl, the piezobiocatalytic platform accelerated selective hydroxylation of ethylbenzene to enantiopure (R)-1-phenylethanol [total turnover number of rAaeUPO (TTN rAaeUPO), 2002; turnover frequency, 77.7 min −1 ; >99% enantiomeric excess (ee)]. The BiOCl−rAaeUPO couple also catalyzed other representative substrates (e.g., propylbenzene, 1-chloro-4-ethylbenzene, cyclohexane, and cis-β-methylstyrene) with high turnover frequency and selectivity. We alleviated the oxidative stress of piezocatalytically generated OH • on rAaeUPO by spatial separation of rAaeUPO and BiOCl, which resulted in greatly enhanced TTN rAaeUPO of >3900 and the notable prolongation of reaction time. Overall, the BiOCl−rAaeUPO couple serves as a mechanical-to-chemical energy conversion platform for driving peroxygenase-catalyzed reactions under ultrasonic conditions.

Organic Sonochemistry: A Chemist’s Timely Perspective on Mechanisms and Reactivity

“… 112 In a recent study, Yoon et al were able to implement a peroxygenase catalyzed oxyfunctionalization that exploits the piezocatalytic generation of H 2 O 2 via oxygen reduction on bismuth oxychloride (BiOCl) under ultrasound (40 kHz, 70 W). 113 Bismuth-based ceramics have gained popularity for transducer applications as improved lead-free ferroelectrics, 114 even though bismuth salts remain underestimated as piezoelectric reagents 115 compared to titanate compounds. 116 An illustration of the oxyfunctionalization reaction is shown in Figure 6 , where ultrasonic activation of BiOCl in aqueous buffer solution containing a recombinant unspecific peroxygenase from Agrocybe aegerite (300 nM) accelerated the selective hydroxylation of ethylbenzene to enantiopure (>99% ee) ( R )-1-phenylethanol.…”

“… Sonication-induced catalytic C–H oxyfunctionalization using piezoelectric BiOCl microsheets plus an unspecific peroxygenase. Reproduced from ref ( 113 ). Copyright 2020 American Chemical Society.…”

Intensivierung von enzymkatalysierten Reaktionen

“…Als alternative Energiequellen zur Rege neration biokatalytischer Reaktionen bieten sich (Sonnen)Licht [10,11] und nachhaltig produzierter Strom an [12,13]. Aber auch unkonventionelle Energiequellen -wie Ultraschall [14,15], Plasmen [16] oder sogar radioaktiver Abfall [17] - könnten Anwen dung finden.…”

Nuclear Waste and Biocatalysis: A Sustainable Liaison?

“…Formic acid, 18 methanol, 19 − 21 H 2 , 22 or electrochemical power 23 − 26 are more attractive from the atom economy point of view. Water oxidation 27 − 29 appears most appealing as here, the atom efficiency is the highest. In this context, the radiolytic formation of H 2 O 2 may represent an interesting alternative method ( Figure 1 a).…”