State Key Laboratory of Fine Chemicals, Zhang Dayu School of Chemistry, Dalian University of Technology, Dalian116024, China.
J Am Chem Soc. 2023 Feb 1;145(4):2170-2182. doi: 10.1021/jacs.2c09348. Epub 2023 Jan 19.
Nature's blueprint provides the fundamental principles for expanding the use of abundant metals in catalysis; however, mimicking both the structure and function of copper enzymes simultaneously in one artificial system for selective C-H bond oxidation faces marked challenges. Herein, we report a new approach to the assembly of artificial monooxygenases utilizing a binuclear CuSCl cluster to duplicate the identical structure and catalysis of the Cu enzyme. The designed monooxygenase Cu-Cl-bpyc facilitates well-defined redox potential that initially activated O photoinduced electron transfer, and generated an active chlorine radical a ligand-to-metal charge transfer (LMCT) process from the consecutive excitation of the formed copper(II) center. The chlorine radical abstracts a hydrogen atom selectively from C(sp)-H bonds to generate the radical intermediate; meanwhile, the O species interacted with the mimic to form mixed-valence species, giving the desired oxidization products with inherent product selectivity of copper monooxygenases and recovering the catalyst directly. This enzymatic protocol exhibits excellent recyclability, good functional group tolerance, and broad substrate scope, including some biological and pharmacologically relevant targets. Mechanistic studies indicate that the C-H bond cleavage was the rate-determining step and the cuprous interactions were essential to stabilize the active oxygen species. The well-defined structural characters and the fine-modified catalytic properties open a new avenue to develop robust artificial enzymes with uniform and precise active sites and high catalytic performances.
自然界的蓝图为拓展丰富金属在催化中的应用提供了基本原理；然而，要在一个人工体系中同时模拟铜酶的结构和功能，以实现对选择性 C-H 键氧化，仍然面临着巨大的挑战。在此，我们报告了一种利用双核 CuSCl 簇组装人工单加氧酶的新方法，以复制铜酶的相同结构和催化作用。设计的单加氧酶 Cu-Cl-bpyc 具有明确的氧化还原电位，可初始激活 O 光诱导电子转移，并生成活性氯自由基，这是一个配体到金属电荷转移（LMCT）过程，来自形成的铜(II)中心的连续激发。氯自由基从 C(sp)-H 键中选择性地夺取一个氢原子，生成自由基中间体；同时，O 物种与模拟物相互作用，形成混合价态物种，生成具有固有铜单加氧酶选择性的所需氧化产物，并直接回收催化剂。该酶促反应表现出优异的可回收性、良好的官能团耐受性和广泛的底物范围，包括一些生物和药理学相关的靶标。机理研究表明，C-H 键的断裂是决速步骤，亚铜相互作用对于稳定活性氧物种至关重要。明确的结构特征和精细修饰的催化性能为开发具有均匀、精确活性位点和高催化性能的稳健人工酶开辟了新途径。
