抗氧化剂清除自由基的作用机理及结构—活性关系研究

【作者】 郭维玲；

【导师】 陈德展；

【作者基本信息】 山东师范大学 ， 物理化学， 2007， 硕士

【摘要】 鉴于清除自由基的重要性,寻找高效、低毒、价廉的抗氧化剂已成为生物、化学、医学等研究领域的重要课题。目前丰富和拓展抗氧化剂种类的途径主要有两种,一种是对原有的抗氧化剂进行结构修饰以提高活性,另一种途径就是找寻和研究安全、无毒、高效的天然植物抗氧化剂。因此,合理设计并深入研究人工合成及天然抗氧化剂清除自由基的机理,以及在此机理基础上总结抗氧化剂的构效关系,能深化对抗氧化剂的认识,加速抗氧化剂的筛选。本文合理设计了一类新型抗氧化剂,用量子化学的密度泛函理论方法研究了合成及一些天然抗氧化剂清除自由基的反应机理,总结了抗氧化剂的结构-活性关系,为寻找设计新颖高效的抗氧化剂,丰富抗氧化剂的种类提供了理论依据。本文的主要研究内容为:1) 4,5-二羟基异喹啉及其衍生物的抗氧化性能研究设计了一类新型抗氧化剂4,5-二羟基异喹啉（DHIQ）和它的一系列衍生物DHIQs,并用密度泛函理论（DFT）研究了它们的结构-活性关系（SAR）。研究表明,DHIQs在清除过氧自由基ROO·时和对应的酚1,8-萘二醇及其衍生物DIOLs有相似的反应活性,却比后者有更高的气态稳定性。因此,DHIQs是一类优良的抗氧化剂,可以认为DHIQ是一个好的抗氧化剂先导结构。2)1,8-萘二醇和4,5-二羟基异喹啉清除·OOCH3反应的过渡态机理研究。用B3LYP/6-311+G（d,p）方法研究了1,8-萘二醇和4,5-二羟基异喹啉清除·OOCH3反应的过渡态及反应机理。通过分析两个抽氢反应过程中各自形成的反应复合物及过渡态的结构和能量,再一次证实了1,8-萘二醇比4,5-二羟基异喹啉清除·OOCH3的活性高;对各反应物种中O₁、O₂、H三种原子上的自旋密度分布和O₁、H、O₂、O₁–H、O₂–H上的电子密度分布进行分析,表明两个反应的反应机理都是直接氢传递（HAT）过程。3)迷迭香中几种抗氧化剂的结构-活性关系研究。对迷迭香中的四种化合物carnosic acid （CSA）、carnosol（CS）、12-methoxyl-trans-carnosic acid（12-MO-Trans-CSA）和12-methoxyl-cis-carnosic acid（12-MO-Cis-CSA）进行了构效关系研究。分析它们的几何结构、电子的自旋密度分布、O-H键的解离焓（bond dissociation enthalpy,简称BDE）表明,它们都是活泼的抗氧化剂;CSA比α-tocopherol（α-TOH）和CS的活性高、CS和α-TOH的活性相当;CSA比CS的活性高,12-MO-Trans-CSA和12-MO-Cis-CSA比苯酚的活性高,研究表明CSA,12-MO-Trans-CSA和12-MO-Cis-CSA的活性较高是由于分子内氢键形成的七元环所致。更多还原

【Abstract】 In view of the importance of scavenging free radicals, now the search of high efficient, low-toxic and inexpensive antioxidants has been one of the substantial subjects in many fields such as biology, chemistry and medicine. There are two ways to enrich the species of antioxidants, one is to increase the activity of antioxidants by improving the structures of them, and the other is to find efficient natural antioxidants. So, the mechanism of antioxidant scavenging free radicals and a preliminary structure-activity relationship should be studied, this will be helpful in order to further the study in this field and accelerate the selection of antioxidants.In this thesis, a new class of antioxidants was designed, the radical- scavenging mechanism of some natural and synthetic antioxidants was investigated on, and the structure-activity relationship （SAR） of them was summarized by quantum chemical computational method DFT. This provides theoretical basis not only for searching and designing novel antioxidants, but also for increasing the species of antioxidants.The main results achieved1) study on the antioxidation of 4, 5-dihydroxyisoquinoline （DHIQ） and its derivativesTo enhance the gas stability of greatly reactive antioxidants, 4, 5-dihydroxyisoq- uinoline （DHIQ） and its derivatives are rationally designed as a new class of antioxidants. The structure-activity relationships （SAR） of the compounds are evaluated by density functional theory （DFT） method. Calculations show that DHIQs have similar reactivity with peroxyl radicals ROO·to that of equivalently substituted phenols 1, 8-naphthalenediols DIOLs ,but higher stability to air oxidation.As a consequence, DHIQs are good antioxidants and DHIQ can be regarded as a potential lead compound.2)Investigation into the transtion states and mechanism of H-atom abstraction by·OOCH3 from 1, 8-naphthalenediol and 4, 5-dihydroxyisoquinoline In this paper, the transtion states and mechanism of H-atom abstraction by·OOCH3 from1, 8-naphthalenediol and 4, 5-dihydroxyisoquinoline were investigated by B3LYP method in 6-311+G （d, p） level. It was confirmed that the reactivity of 1, 8-naphthalenediol is higher than that of 4, 5-dihydroxyisoquinoline by analyzing the structures and energy of their transtion states and intermediate hydrogen-bonded complexes which were formed in the processing of H-atom abstraction. It was also revealed that the mechanism is a direct H-atom tranferring processing （HAT） by analyzing the spin density of the O₁ ,O₂ and H ,as well the electron density of O₁, H, O₂, O₁–H and O₂–H.3)A study on the structure-activity relationships of a few of antioxidants in natural plant rosemaryA study on the structure-activity relationship of carnosic acid （CSA）, carnosol （CS）, 12-methoxyl-trans-carnosic acid （12-MO-Trans-CSA） and12- methoxyl-cis-carnosic acid （12-MO-Cis-CSA） as antioxidants was performed. It was indicated that CSA and CS are active antioxidants by investigating the geometry of ground state molecules and their radicals, the electron spin density distribution of the radicals, and the O-H bond dissociation enthalpy （BDE）; the antioxidative activity of CSA is higher than that of CS andα-tocopherol （α-TOH）, and the activity of CS is nearly indentical to that ofα-TOH by comparing their O-H BDEs; the seven-member ring formed by intramolecular hydrogen-bond leads to the higher activity of CSA than that of CS, as well 12-MO-Trans-CSA and 12-MO-Cis-CSA than that of phenol.更多还原