School of Chemical Sciences , University of Illinois at Urbana-Champaign , 600 South Mathews Avenue , Urbana , Illinois 61801 , United States.
Department of Chemistry , University of Saint Thomas , 2115 Summit Avenue , Saint Paul , Minnesota 55105 , United States.
J Am Chem Soc. 2019 Apr 24;141(16):6639-6650. doi: 10.1021/jacs.9b01516. Epub 2019 Apr 10.
The characterization of high-valent iron centers in enzymes has been aided by synthetic model systems that mimic their reactivity or structural and spectral features. For example, the cleavage of dioxygen often produces an iron(IV)-oxo that has been characterized in a number of enzymatic and synthetic systems. In non-heme 2-oxogluterate dependent (iron-2OG) enzymes, the ferryl species abstracts an H-atom from bound substrate to produce the proposed iron(III)-hydroxo and caged substrate radical. Most iron-2OG enzymes perform a radical rebound hydroxylation at the site of the H-atom abstraction (HAA); however, recent reports have shown that certain substrates can be desaturated through the loss of a second H atom at a site adjacent to a heteroatom (N or O) for most native desaturase substrates. One proposed mechanism for the removal of the second H-atom involves a polar-cleavage mechanism (electron transfer-proton transfer) by the iron(III)-hydroxo, as opposed to a second HAA. Herein we report the synthesis and characterization of a series of iron complexes with hydrogen bonding interactions between bound aquo or hydroxo ligands and the secondary coordination sphere in ferrous and ferric complexes. Interconversion among the iron species is accomplished by stepwise proton or electron addition or subtraction, as well as H-atom transfer (HAT). The calculated bond dissociation free energies (BDFEs) of two ferric hydroxo complexes, differentiated by their noncovalent interactions and reactivity, suggest that neither complex is capable of activating even weak C-H bonds, lending further support to the proposed mechanism for desaturation in iron-2OG desaturase enzymes. Additionally, the ferric hydroxo species are differentiated by their reactivity toward performing a radical rebound hydroxylation of triphenylmethylradical. Our findings should encourage further study of the desaturase systems that may contain unique H-bonding motifs proximal to the active site that help bias substrate desaturation over hydroxylation.
高价位铁中心在酶中的特性已通过模拟其反应性或结构和光谱特征的合成模型系统得到帮助。例如，氧气的分解通常会产生一种铁（IV）-氧，这种物质已经在许多酶和合成系统中得到了描述。在非血红素 2-氧代戊二酸依赖性（铁-2OG）酶中，过铁物种从结合的底物中提取一个 H-原子，产生所提出的铁（III）-羟和笼状底物自由基。大多数铁-2OG 酶在 H-原子提取的位置（HAA）进行自由基反弹羟化；然而，最近的报道表明，某些底物可以通过在紧邻杂原子（N 或 O）的位置失去第二个 H 原子而不饱和，对于大多数天然去饱和酶底物。第二个 H-原子的去除的一个提出的机制涉及铁（III）-羟的极性断裂机制（电子转移-质子转移），而不是第二个 HAA。在此，我们报告了一系列铁配合物的合成和特性，这些配合物具有与亚铁和三价铁配合物的次级配位球之间的氢键相互作用。通过逐步质子或电子添加或减去，以及 H-原子转移（HAT），铁物种之间的相互转化。两个铁羟配合物的计算键离解自由能（BDFEs），通过它们的非共价相互作用和反应性进行区分，表明没有一个配合物能够激活甚至弱的 C-H 键，这进一步支持了铁-2OG 去饱和酶中去饱和的提出的机制。此外，铁羟配合物的反应性不同，可对三苯甲基自由基进行自由基反弹羟化。我们的发现应该鼓励进一步研究可能含有靠近活性位点的独特氢键模式的去饱和酶系统，这些模式有助于使底物不饱和而不是羟化。
