Catalytic performance of ThDP-AuCl : integration with MenD enzyme, modification, and exploration of alternative NHC-AuCl complexes

Abstract

N-heterocyclic carbene (NHC)-gold catalysts are renowned for facilitating hydrofunctionalization reactions. Thiamine diphosphate (ThDP), a phosphate-containing NHC, can enhance solubility in non-organic solvents and serves as a coenzyme for various enzymes. We synthesized and characterized ThDP-AuCl and investigated its catalytic performance both as an isolated catalyst and in conjunction with enzymes such as BsMenD to form artificial metalloenzymes (ArMs). Catalytic activity tests using HPLC and NMR revealed that ThDP-AuCl effectively catalyzed hydroamination and hydroalkoxylation reactions. However, ThDP-AuCl integrated into ArMs with BsMenD proteins showed no catalytic activity, likely due to interactions between cysteine thiol groups and the gold complex. Modifying cysteine residues did not resolve this issue, prompting further exploration. Additionally, inspired by recent studies on counterions' influence on NHC-Au(I)-catalyzed reactions, Thiamine-AuX and NBT-AuX (X=Br, I, OTs) were tried to synthesized and other counterions for further synthesis. The aim is to elucidate the catalytic effects of different counterions on NHC-AuX compounds, potentially leading to more efficient catalytic systems.

Date of Award	2024
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology
Supervisor	Zhihong GUO (Supervisor)