Turning the band alignment of carbon dots for visible-light-driven enzymatic asymmetric reduction of aromatic ketone

Li Qiao; Bianqin Ma; Yongjian Jiang; Xiaoting Pan; Zhili Mao; Yi Zhang; Roger A Sheldon; Anming Wang

doi:10.1016/j.ijbiomac.2024.139444

Turning the band alignment of carbon dots for visible-light-driven enzymatic asymmetric reduction of aromatic ketone

Int J Biol Macromol. 2025 Jan 4:139444. doi: 10.1016/j.ijbiomac.2024.139444. Online ahead of print.

Authors

Li Qiao¹, Bianqin Ma², Yongjian Jiang², Xiaoting Pan², Zhili Mao², Yi Zhang³, Roger A Sheldon⁴, Anming Wang⁵

Affiliations

¹ Hunan Provincial Key Laboratory of Micro & Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, PR China; Key Laboratory of Organosilicon Chemistry and Materials Technology, Ministry of Education; College of Materials Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
² Key Laboratory of Organosilicon Chemistry and Materials Technology, Ministry of Education; College of Materials Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China.
³ Hunan Provincial Key Laboratory of Micro & Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, PR China. Electronic address: yzhangcsu@csu.edu.cn.
⁴ Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits, 2050 Johannesburg, South Africa; Department of Biotechnology, Section BOC, Delft University of Technology, van der Maasweg 9, 2629, HZ, Delft, the Netherlands. Electronic address: roger.sheldon@wits.ac.za.
⁵ Key Laboratory of Organosilicon Chemistry and Materials Technology, Ministry of Education; College of Materials Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China. Electronic address: 11837066@zju.edu.cn.

PMID: 39761903
DOI: 10.1016/j.ijbiomac.2024.139444

Abstract

Keto reductases are crucial NAD(P)H-dependent enzymes used for the enantioselective synthesis of alcohols from prochiral ketones. Typically, the NADPH cofactor is regenerated through a second enzyme and/or substrate. However, photocatalytic cofactor regeneration using water as a sacrificial electron and hydrogen donor presents a promising alternative, albeit a challenging one. Herein we fabricated several nitrogen-doped carbon dots (CDs) with visible light absorption properties, good water solubility and biocompatibility for photocatalytic regeneration of NADPH. The CD with a smaller size and suitable redox potential gave the highest NADPH yield (55.7 %). Based on this, NADPH-dependent aldo-keto reductase crosslinked aggregates (AKR-CLEs) were initially applied as a stable biocatalyst to reduce the prochiral ketone. (S)-1-(2-Chlorophenyl) ethanol, an intermediate for LPA1R antagonists, was obtained in 65.3 % yield and 99.99 % enantiomeric excess (ee) under visible light irradiation. The isotope tracer experiment confirmed that water is the hydrogen donor in this light-driven, photo-enzymatic asymmetric hydrogenation system. This method is useful for the sustainable synthesis of chiral alcohols. Moreover, the general principle of utilizing water as the sacrificial hydrogen and electron donor holds potential for application in other redox cofactor regeneration systems.

Keywords: Aldo-keto reductase; Bio-photo-hybridization system; Chiral alcohol; Photo-enzymatic catalysis.