本文關(guān)鍵詞： “picket fence”卟啉衍生物 分子識別 溶劑效應　出處：《中國協(xié)和醫(yī)科大學》2008年博士論文　論文類型：學位論文

【摘要】： 柵欄狀(Picket fence)卟啉由于四周被保護起來形成中空的籠腔結(jié)構(gòu),當軸向配體鍵合到卟啉環(huán)平面時,除了中心的軸向配位作用外,軸向配體與柵欄結(jié)構(gòu)所構(gòu)成的籠腔之間會產(chǎn)生額外的相互作用,這種額外作用會強化柵欄卟啉體系的分子識別能力。以往的研究表明該籠型結(jié)構(gòu)不僅對中性分子具有識別作用,而且對于陰離子有很強的作用。氨基酸作為生物蛋白的組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為柵欄結(jié)構(gòu),可增強所合成的卟啉體系的生物相容性�；谶@一目的,我們設(shè)計并合成了氨基酸“picketfnece”卟啉,并研究了它們的分子識別作用。 本論文以Boc保護的氨基酸為柵欄結(jié)構(gòu),采用DCC縮合的方法,合成了5種“picket fence”結(jié)構(gòu)的卟啉化合物。并作為主體分子,探討了它們對F~-、Cl~-、Br~-、I~-、H_2SO_4~-、AcO~-、H_2PO_4~-這七種陰離子的識別行為。結(jié)果表明,這一系列模型化合物對陰離子具有很強的識別作用,結(jié)合常數(shù)達到了10~5。數(shù)量級。在這七種陰離子中,不同的化合物對F~-、Cl~-離子表現(xiàn)出選擇性的識別行為。 金屬離子嵌入卟啉環(huán)中心以后具有非常重要的生理活性。以Boc保護的甘氨酸“picket fence”卟啉化合物為例,合成了其五種金屬卟啉復合物�？紤]到Cl~-作為人體內(nèi)唯一的陰離子通道,具有非常重要的生理學作用,所以被選擇作為客體分子來研究。與其自由堿基卟啉化合物一樣,對Cl~-也具有識別作用(除了銅卟啉以外)。為了探討識別的機理,研究了自由堿基卟啉在六種不同極性溶劑(甲苯、四氫呋喃、二氯甲烷、乙腈、乙醇和四氫呋喃-水(1:1 v/v))中對Cl~-的識別行為。實驗結(jié)果表明:在非質(zhì)子性溶劑,如甲苯、四氫呋喃、二氯甲烷和乙腈中均有較強的鍵合能力,而在質(zhì)子性溶劑,如乙醇和四氫呋喃-水(1:1 v/v)混合溶劑,紫外-可見滴定圖譜上沒有檢測到變化。因此可以得出:此化合物是一種以氫鍵為主要作用力的模型化合物,由于乙醇和四氫呋喃-水(1:1 v/v)混合溶劑中的水分子均提供了過量的氫鍵,替代了Cl~-與柵欄中酰胺鍵間的相互作用,因而在這兩種溶劑中沒有鍵合Cl~-的現(xiàn)象。這一結(jié)果表明,Boc保護的氨基酸“picket fence”卟啉與C1~-間的相互作用以氫鍵為主。 同時,“picket fence”卟啉化合物也是相對較好的肌紅蛋白和血紅蛋白模型。一個協(xié)同鍵合氧氣的生物學相關(guān)模型將揭示滿足協(xié)同性所需的最簡單的結(jié)構(gòu),也有助于較好地理解血紅蛋白中變構(gòu)控制所需的能量。 本文成功的制備了一種通過酯鍵鏈接的含有四個特戊�；鶠闁艡诮Y(jié)構(gòu)的“Picket fence”卟啉體系和能夠與之進行配位的兩種多堿基卟啉配體。使現(xiàn)有的合成模型化合物更接近血紅蛋白的鍵合機理,可以試探性的模擬血紅蛋白的四個血紅素協(xié)同結(jié)合氧氣的過程,對人工血液替代品的研究提供基礎(chǔ)理論性的探索更有意義。
[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.
【學位授予單位】：中國協(xié)和醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2008
【分類號】：R313

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