State Key Laboratory of Organic-Inorganic Composites, Key Lab of Biomedical Materials of Natural Macromolecules (Beijing University of Chemical Technology, Ministry of Education), Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, P. R. China.
Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, P. R. China.
J Mater Chem B. 2023 Aug 2;11(30):7117-7125. doi: 10.1039/d3tb00780d.
The design of artificial biocatalysts with enzyme-like active sites and catalytic functions has long been an attractive yet challenging goal. In this study, we present a nucleotide-Cu complex, synthesized through a one-pot approach, capable of catalyzing -hydroxylation reactions resembling those of minimalist monooxygenases. Both experimental and theoretical findings demonstrate that the catalyst, in which Cu coordinates with both the nucleobase and phosphate moieties, forms a ternary-complex intermediate with HO and tyramine substrates through multiple weak interactions. The subsequent electron transfer and hydrogen (or proton) transfer steps lead to the -hydroxylation of tyramine, where the single copper center exhibits a similar function to natural dicopper sites. Moreover, Cu bound to nucleotides or oligonucleotides exhibits thermophilic catalytic properties within the temperature range of 25 °C to 75 °C, while native enzymes are fully deactivated above 35 °C. This study may provide insights for the future design of oxidase-mimetic catalysts and serve as a guide for the design of primitive metallocentre-dependent enzymes.
具有酶样活性位点和催化功能的人工生物催化剂的设计一直是一个有吸引力但具有挑战性的目标。在这项研究中，我们通过一锅法合成了一种核苷酸-Cu 配合物，能够催化类似于最小单加氧酶的 -羟化反应。实验和理论研究结果表明，催化剂中 Cu 与碱基和磷酸部分配位，通过多种弱相互作用与 HO 和酪胺底物形成三元复合物中间体。随后的电子转移和氢（或质子）转移步骤导致酪胺的 -羟化，其中单个铜中心表现出类似于天然双核位点的功能。此外，与核苷酸或寡核苷酸结合的 Cu 在 25°C 至 75°C 的温度范围内表现出嗜热催化特性，而天然酶在 35°C 以上完全失活。这项研究可为氧化酶模拟催化剂的未来设计提供思路，并为原始金属中心依赖性酶的设计提供指导。
