Molecular Modelling Group, Indian Institute of Chemical Technology, Hyderabad 500-607, India.
J Phys Chem A. 2012 Jan 12;116(1):582-91. doi: 10.1021/jp208230g. Epub 2011 Dec 12.
In this work, we present the first computational study on a biomimetic cysteine dioxygenase model complex, Fe(II)(LN(3)S), in which LN(3)S is a tetradentate ligand with a bis(imino)pyridyl scaffold and a pendant arylthiolate group. The reaction mechanism of sulfur dioxygenation with O(2) was examined by density functional theory (DFT) methods and compared with results obtained for cysteine dioxygenase. The reaction proceeds via multistate reactivity patterns on competing singlet, triplet, and quintet spin state surfaces. The reaction mechanism is analogous to that found for cysteine dioxygenase enzymes (Kumar, D.; Thiel, W.; de Visser, S. P. J. Am. Chem. Soc. 2011, 133, 3869-3882); hence, the computations indicate that this complex can closely mimic the enzymatic process. The catalytic mechanism starts from an iron(III)-superoxo complex and the attack of the terminal oxygen atom of the superoxo group on the sulfur atom of the ligand. Subsequently, the dioxygen bond breaks to form an iron(IV)-oxo complex with a bound sulfenato group. After reorganization, the second oxygen atom is transferred to the substrate to give a sulfinic acid product. An alternative mechanism involving the direct attack of dioxygen on the sulfur, without involving any iron-oxygen intermediates, was also examined. Importantly, a significant energetic preference for dioxygen coordinating to the iron center prior to attack at sulfur was discovered and serves to elucidate the function of the metal ion in the reaction process. The computational results are in good agreement with experimental observations, and the differences and similarities of the biomimetic complex and the enzymatic cysteine dioxygenase center are highlighted.
在这项工作中，我们首次对仿生半胱氨酸双加氧酶模型配合物 Fe(II)(LN(3)S) 进行了计算研究，其中 LN(3)S 是一种具有双（亚氨基）吡啶骨架和一个悬垂芳硫醇基团的四齿配体。通过密度泛函理论 (DFT) 方法研究了与 O(2) 的硫双加氧反应的反应机制，并将结果与半胱氨酸双加氧酶的结果进行了比较。反应通过竞争单重态、三重态和五重态自旋态表面上的多态反应模式进行。反应机制类似于在半胱氨酸双加氧酶酶中发现的机制（Kumar, D.; Thiel, W.; de Visser, S. P. J. Am. Chem. Soc. 2011, 133, 3869-3882）；因此，计算表明该配合物可以很好地模拟酶促过程。催化机制从铁(III)-过氧络合物开始，过氧基团的末端氧原子攻击配体的硫原子。随后，二氧键断裂形成与结合的亚磺酸盐基团的铁(IV)-氧络合物。重排后，第二个氧原子转移到底物上生成亚磺酸产物。还检查了一种涉及二氧直接攻击硫而不涉及任何铁-氧中间体的替代机制。重要的是，发现了二氧优先与铁中心配位然后再攻击硫的显著能量偏好，并阐明了金属离子在反应过程中的功能。计算结果与实验观察结果吻合良好，并突出了仿生配合物和酶对半胱氨酸双加氧酶中心的差异和相似之处。
