α-酮酸氧化酶的催化氧化机理以及几种金属离子与硫脲衍生物相互作用的理论研究

发布时间：2018-10-25 06:37

【摘要】：非血红素加氧酶是一种能够结合氧气的铁氧化酶,对非血红素加氧酶的研究大大促进了人们对酶促反应的理解,α-酮酸加氧酶属于非血红素铁加氧酶家族中的重要分支,在生命科学中起到重要作用,参与了生物体内分解代谢的重要过程。α-酮酸加氧酶可以催化底物的氧化脱羧、烷烃的羟基化以及烯烃的环氧化等,对羟基苯基丙酮酸氧化酶(HPPD)和羟基扁桃酸乙酯合酶(HMS)属于α-酮酸加氧酶中重要的组成部分。本文主要介绍了两种特殊的α-酮酸加氧酶,HPPD和HMS。通过对HPPD催化氧化反应过程的研究,揭示了具体的反应机理,探索了抑制剂的作用机理,为寻找新型HPPD抑制剂提供了理论基础。同时对HMS的仿生模型分子进行理论研究,讨论了仿生模型催化氧化过程的反应机理,有助于人们从分子水平上理解自然界中氧分子的活化机理,便于研究者合成高效催化剂。硫脲衍生物在农业、医学、工业等领域发挥着不可取代的作用,本文研究了硫脲衍生物与几种金属离子的配位性质,以期待找到相关规律。第一章主要概述了本文研究中所用到的量子化学理论基础以及计算方法,并介绍了α酮酸加氧酶-HPPD、HPPD抑制剂、酶的仿生模型分子以及硫脲衍生物的研究情况。第二章运用密度泛函理论研究了HPPD的催化氧化过程以及抑制剂的作用机理,探索反应过程中基团转移的途径,确定了反应过程的过渡态性质,获得前线轨道信息及键长、键角、电荷等分子构型参数,明确反应的势能面特征,确定最低能量反应通道,确定整个过程的最低能量反应途径,从而澄清实验上HPPD以及抑制剂的反应过程。第三章运用密度泛函理论研究了羟基扁桃酸乙酯合酶(HMS)的仿生模型[(Tpph,Me)Fe II(PPH)]通过两步加氧以及氧化脱羧过程,计算化学反应过程中的驻点的键长、键角、电荷等主要构型参数,分析比较HMS与仿生模型的反应机理过程发现,仿生模型[(Tpph,Me)FeII(PPH)]的第一步脱羧反应与HMS的反应机理一致。第四章研究了三种双硫脲衍生物分别与锌离子、镍离子以及铜离子的配位情况,经过计算获得配合物的键长、键角、电荷、结合能以及前线轨道等构型参数,结果发现,双硫脲衍生物(Tha)与锌离子、镍离子形成六配位的八面体构型,但与铜离子不能形成配合物;双硫脲衍生物(Thb)与锌离子、镍离子形成四配位化合物,与铜离子形成六配位化合物;双硫脲衍生物(Thc)与三种金属离子形成了四配位化合物。经分析比较发现,铜离子不同的配位方式是因为采取了不同的杂化方式。第五章是对全文内容进行了总结概括,并对本文中的不足之处进行了说明,对之后工作计划做出了规划。
[Abstract]:Non-heme oxygenase is a kind of iron oxidase that binds oxygen. The study of non-heme oxygenase greatly promotes the understanding of enzymatic reaction. 伪 -ketoxygenase belongs to the important branch of non-heme ferric oxygenase family. 伪 -ketoacid oxygenase can catalyze oxidative decarboxylation of substrates, hydroxylation of alkanes and epoxidation of olefins. P-hydroxyphenyl pyruvate oxidase (HPPD) and hydroxyl mandelic acid ethyl ester synthase (HMS) are important components of 伪 -ketoxygenase. In this paper, two special 伪 -ketoxylate oxygenases, HPPD and HMS., are introduced. Through the study of the process of HPPD catalytic oxidation, the specific reaction mechanism was revealed, and the mechanism of action of the inhibitor was explored, which provided a theoretical basis for finding a new type of HPPD inhibitor. At the same time, a theoretical study on the biomimetic model molecule of HMS was carried out, and the reaction mechanism of the catalytic oxidation process of the bionic model was discussed, which was helpful to understand the activation mechanism of oxygen molecules in nature at the molecular level and to facilitate the researchers to synthesize high efficient catalysts. Thiourea derivatives play an irreplaceable role in agriculture, medicine and industry. In this paper, the coordination properties of thiourea derivatives with several metal ions are studied in order to find out the relevant rules. In the first chapter, the theoretical basis and calculation methods of quantum chemistry used in this study are summarized, and the studies of 伪 -ketoxygenase-HPPD,HPPD inhibitors, biomimetic model molecules of enzymes and thiourea derivatives are introduced. In chapter 2, the catalytic oxidation process of HPPD and the action mechanism of the inhibitor are studied by using density functional theory, and the mechanism of group transfer in the reaction process is explored. The transition state properties of the reaction process are determined, and the frontier orbital information, bond length and bond angle are obtained. The molecular configuration parameters such as charge, the characteristics of potential energy surface of the reaction, the lowest energy reaction channel and the lowest energy reaction path of the whole process are determined, thus clarifying the reaction process of HPPD and inhibitor in experiments. In chapter 3, the bionic model [(Tpph,Me) Fe II (PPH)] of ethyl hydroxyl mandelate synthase (HMS) is studied by means of density functional theory (DFT). The main configuration parameters, such as bond length, bond angle, charge and so on, are calculated by two-step oxygenation and oxidative decarboxylation. By analyzing and comparing the reaction mechanism of HMS and bionic model, it is found that the first step decarboxylation reaction of bionic model [(Tpph,Me) FeII (PPH)] is consistent with that of HMS. In chapter 4, the coordination of three kinds of bisthiourea derivatives with zinc ion, nickel ion and copper ion is studied. The bond length, bond angle, charge, binding energy and frontier orbital configuration parameters of the complexes are obtained. Dithiourea derivative (Tha) forms hexahedral octahedral configuration with zinc ion and nickel ion, but it can't form complex with copper ion, (Thb) derivative of bisthiourea derivative forms four coordination compound with zinc ion, nickel ion form six coordination compound, and copper ion form hexahedron compound. (Thc), a bisthiourea derivative, forms four coordination compounds with three metal ions. By analysis and comparison, it is found that different coordination modes of copper ions are due to different hybrid modes. The fifth chapter summarizes the content of the full text, explains the shortcomings of this paper, and makes a plan for the later work plan.
【学位授予单位】：鲁东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：Q55;O621.13

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