“picket fence”卟啉衍生物的合成及其分子识别作用

发布时间：2018-01-20 01:34

本文关键词： “picket fence”卟啉衍生物分子识别溶剂效应　出处：《中国协和医科大学》2008年博士论文　论文类型：学位论文

【摘要】： 栅栏状(Picket fence)卟啉由于四周被保护起来形成中空的笼腔结构,当轴向配体键合到卟啉环平面时,除了中心的轴向配位作用外,轴向配体与栅栏结构所构成的笼腔之间会产生额外的相互作用,这种额外作用会强化栅栏卟啉体系的分子识别能力。以往的研究表明该笼型结构不仅对中性分子具有识别作用,而且对于阴离子有很强的作用。氨基酸作为生物蛋白的组成部分具有很好的生物相容性和特定的生物功能。因此,向卟啉化合物中引入氨基酸作为栅栏结构,可增强所合成的卟啉体系的生物相容性。基于这一目的,我们设计并合成了氨基酸“picketfnece”卟啉,并研究了它们的分子识别作用。本论文以Boc保护的氨基酸为栅栏结构,采用DCC缩合的方法,合成了5种“picket fence”结构的卟啉化合物。并作为主体分子,探讨了它们对F~-、Cl~-、Br~-、I~-、H_2SO_4~-、AcO~-、H_2PO_4~-这七种阴离子的识别行为。结果表明,这一系列模型化合物对阴离子具有很强的识别作用,结合常数达到了10~5。数量级。在这七种阴离子中,不同的化合物对F~-、Cl~-离子表现出选择性的识别行为。金属离子嵌入卟啉环中心以后具有非常重要的生理活性。以Boc保护的甘氨酸“picket fence”卟啉化合物为例,合成了其五种金属卟啉复合物。考虑到Cl~-作为人体内唯一的阴离子通道,具有非常重要的生理学作用,所以被选择作为客体分子来研究。与其自由碱基卟啉化合物一样,对Cl~-也具有识别作用(除了铜卟啉以外)。为了探讨识别的机理,研究了自由碱基卟啉在六种不同极性溶剂(甲苯、四氢呋喃、二氯甲烷、乙腈、乙醇和四氢呋喃-水(1:1 v/v))中对Cl~-的识别行为。实验结果表明:在非质子性溶剂,如甲苯、四氢呋喃、二氯甲烷和乙腈中均有较强的键合能力,而在质子性溶剂,如乙醇和四氢呋喃-水(1:1 v/v)混合溶剂,紫外-可见滴定图谱上没有检测到变化。因此可以得出:此化合物是一种以氢键为主要作用力的模型化合物,由于乙醇和四氢呋喃-水(1:1 v/v)混合溶剂中的水分子均提供了过量的氢键,替代了Cl~-与栅栏中酰胺键间的相互作用,因而在这两种溶剂中没有键合Cl~-的现象。这一结果表明,Boc保护的氨基酸“picket fence”卟啉与C1~-间的相互作用以氢键为主。同时,“picket fence”卟啉化合物也是相对较好的肌红蛋白和血红蛋白模型。一个协同键合氧气的生物学相关模型将揭示满足协同性所需的最简单的结构,也有助于较好地理解血红蛋白中变构控制所需的能量。本文成功的制备了一种通过酯键链接的含有四个特戊酰基为栅栏结构的“Picket fence”卟啉体系和能够与之进行配位的两种多碱基卟啉配体。使现有的合成模型化合物更接近血红蛋白的键合机理,可以试探性的模拟血红蛋白的四个血红素协同结合氧气的过程,对人工血液替代品的研究提供基础理论性的探索更有意义。
[Abstract]:Picket fence- porphyrin is protected around the palisade to form a hollow cage cavity structure. When the axial ligand is bonded to the porphyrin ring plane, the center of the porphyrin ring, in addition to the axial coordination action. There is an additional interaction between the axial ligand and the cage cavity formed by the palisade structure. This extra action will enhance the molecular recognition ability of the palisade porphyrin system. Previous studies have shown that the cage structure not only can recognize neutral molecules. Amino acids as a component of biological proteins have good biocompatibility and specific biological functions. Therefore, amino acids are introduced into porphyrin compounds as palisade structure. For this purpose, we designed and synthesized amino acid "picketfnece" porphyrin and studied their molecular recognition. In this paper, five kinds of porphyrin compounds with "picket fence" structure were synthesized using Boc protected amino acids as palisade structures and DCC condensation as host molecules. The recognition behavior of these seven kinds of anions is discussed in this paper. This series of model compounds have strong recognition to anions with binding constants of 10 ~ 5. In these seven kinds of anions, different compounds have different F-. Cl-ion exhibits selective recognition behavior. Metal ions have very important physiological activity after intercalation of porphyrin ring center. Take glycine "picket fence" porphyrin compound protected by Boc as an example. Five kinds of metalloporphyrin complexes have been synthesized. Considering that Cl- is the only anion channel in human body, it has very important physiological function. Therefore, they were selected as guest molecules to study. Just like their free base porphyrin compounds, they also have the ability to recognize Cln- (in addition to copper porphyrin), in order to explore the mechanism of recognition. Free base porphyrin in six different polar solvents (toluene, tetrahydrofuran, dichloromethane, acetonitrile) was studied. The recognition behavior of Cl- in ethanol and tetrahydrofuran-water 1: 1 vv.Experimental results show that in non-proton solvents such as toluene and tetrahydrofuran. Both dichloromethane and acetonitrile have strong bonding ability, but they are mixed in proton solvents such as ethanol and tetrahydrofurane-water (1: 1 / v). No changes were detected in the UV-Vis titration. Therefore, it can be concluded that this compound is a model compound with hydrogen bond as the main force. Since the water molecules in ethanol and tetrahydrofuran-water 1: 1 / v) mixture provide excessive hydrogen bonds, they replace the interaction between Cln- and amide-bonds in the palisade. Therefore, there is no bonding of Cln- in these two solvents. The interaction between Boc protected amino acid "picket fence" porphyrin and C _ 1 ~ (1 +) is mainly hydrogen bond. At the same time. "picket fence" Porphyrin compounds are also relatively good models of myoglobin and hemoglobin. A biological model of co-bonding oxygen will reveal the simplest structure needed to satisfy the synergism. It also contributes to a better understanding of the energy required for allosteric control in hemoglobin. In this paper, we have successfully prepared a kind of "Picket fence" with four tervalyl groups as palisade structure linked by ester bond. Porphyrin system and two kinds of polybasic porphyrin ligands which can coordinate with porphyrin make the existing synthetic model compounds closer to the binding mechanism of hemoglobin. It can tentatively simulate the process of hemoglobin co-binding with oxygen, which provides a theoretical basis for the study of artificial blood substitutes.
【学位授予单位】：中国协和医科大学
【学位级别】：博士
【学位授予年份】：2008
【分类号】：R313

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