Department of Chemistry, St. Edward's University, 3001 South Congress Ave, Austin, TX 78704, United States of America.
Department of Chemistry, CASCaM, University of North Texas, 1508 W. Mulberry Street, Denton, TX 76203, United States of America.
J Inorg Biochem. 2020 Nov;212:111253. doi: 10.1016/j.jinorgbio.2020.111253. Epub 2020 Sep 14.
We report the synthesis and biomimetic activity of a family of model complexes with relevance to acireductone dioxygenase (ARD), an enzyme that displays dual function based on metal identity found in the methionine salvage pathway (MSP). Three complexes with related structural motifs were synthesized and characterized derived from phenolate, and pyridine NO Schiff-base ligands. They display pseudo-octahedral Ni(II)-NO ligand coordination with water at the sixth site, in close alignment to the structure in the resting state of ARD. The three featured complexes exhibit carbon‑carbon bond cleavage activation of lithium acetylacetonate, which was used as a model enzyme substrate. Computationally derived mechanistic routes for the observed reactivity consistent with experimental conditions are herein proposed. The mechanism suggests the possibility of Ni(II)-substrate interactions, followed by oxygen insertion. These results constitute only the third functional model system of ARD, in an attempt to further advance biomimetic contributions to the ongoing debate of ARD's unique metal mediated, regioselective oxidative cleavage.
我们报告了一类与还原酮双加氧酶（ARD）相关的模型配合物的合成和仿生活性，ARD 是一种基于甲硫氨酸补救途径（MSP）中发现的金属特性表现出双重功能的酶。我们合成并表征了三种具有相关结构基序的配合物，它们衍生自苯并酚和吡啶 NO 希夫碱配体。它们表现出拟八面体 Ni(II)-NO 配体配位，第六位为水分子，与 ARD 静止状态的结构非常吻合。这三种配合物都能激活锂乙酰丙酮的碳-碳键断裂，这被用作模型酶底物。本文提出了与实验条件一致的观察到的反应性的计算推导的机理途径。该机理表明 Ni(II)-底物相互作用的可能性，随后是氧插入。这些结果构成了 ARD 的第三个功能模型体系，旨在进一步推进对 ARD 独特的金属介导、区域选择性氧化裂解的持续争论的仿生学贡献。
