【作者】 陈芝红；

【导师】 何永炳；

【作者基本信息】 武汉大学 ， 有机化学， 2010， 博士

【摘要】 阴离子广泛存在于自然界和生物体内,对人类和生物的生存起到了十分重要的作用,阴离子识别和检测在医学,药学和生物学上具有十分重要意义,设计和合成具有选择性识别不同阴离子的超分子主体化合物成为超分子化学研究的重要内容之一。相对于阳离子,阴离子具有大的离子半径,复杂几何构型,高的溶剂化能和易受pH影响等特点,阴离子客体的选择性识别要比金属阳离子的识别存在更大更多的挑战。通过设计和合成超分子主体化合物并用于阴离子选择性检测近年来取得了重要的进展。基于超分子化合物主体的预组织性和主客体空间互补性,主体化合物通过氢键,疏水作用,范德华力等分子间非共价键与客体阴离子相结合。具有光学响应的阴离子受体在阴离子识别研究中起到十分重要的作用,通过主体分子的信号单元所输出的荧光,紫外等信号,可以方便快捷的获得主客体相互作用信息。手性是大多数生物分子的基本属性,手性阴离子识别是指手性主体化合物对外消旋客体化合物阴离子中的一种对映体在空间和能量上存在有利的作用力,而另一种则存在空间和能量上较不利作用力的识别作用。通过手性识别可以帮助了解一些生物体内的生物催化过程；通过手性识别可以检测手性分子的对映体纯度,在手性药物和手性催化剂的筛选和开发上起到重要作用。自然界和生物体内重要阴离子都是存在于水溶液环境中的,对于大多数已报道阴离子受体,在有机溶剂中(DMSO,乙腈,氯仿等)能够通过氢键与阴离子产生选择性识别,尽管这些中性阴离子受体展现出对不同结构的阴离子客体优良的选择性识别和光学响应性能,但这些受体与阴离子的相互作用只能在有机介质中进行,在极性质子性溶剂(水,醇)中,由于溶剂对氢键的破坏作用,这就极大地限制了这类受体在水或生理pH介质中的实际应用。因此合成水溶性的阴离子传感器具有十分重要意义。本论文设计合成了十一个手性或非手性的阴离子受体,包括四个含有硫脲单元的手性阴离子受体和七个水溶性金属络合物受体。通过核磁,红外,质谱等方法对其结构进行了表征。通过使用紫外光谱,荧光光谱,核磁氢谱,质谱和圆二色谱等检测方法研究了这些受体对客体阴离子的识别性能。本论文一共分为六章,主要内容如下：1.综述了阴离子光化学传感器的设计原理和近年来的发展状况,介绍各种不同类型的阴离子光化学传感器及其与各种客体阴离子作用原理,并在此基础上提出了本论文的设计思路。2.通过将手性丙氨酸,硫脲和信号单元引入到吡啶和苯骨架中,合成了四种超分子主体化合物Ⅱ-1、Ⅱ-2、Ⅱ-3、Ⅱ-4,分别通过荧光(Ⅱ-1、Ⅱ-2)、紫外(Ⅱ-3、Ⅱ-4)光谱和核磁研究了主体对客体的手性识别性能。主客体通过多重氢键相互作用,形成1：1络合。主体化合物Ⅱ-1和Ⅱ-2对客体阴离子对映体不同的荧光响应,表现出对客体阴离子一定的对映选择性识别能力；而主体Ⅱ-3和Ⅱ-4,由于对硝基苯的拉电子作用,使得体系硫脲酸性增强,表现出对客体更强的结合能力,对手性客体阴离子也显示出对映选择性识别能力,特别是主体化合物Ⅱ-3,对扁桃酸和丙氨酸表现出良好的手性识别能力。由于对D-,L-构型扁桃酸和丙氨酸不同的生色响应,受体Ⅱ-3可用作这两种手性阴离子的生色传感器。由于受体Ⅱ-3对Boc-谷氨酸和天冬氨酸Boc-NH的手性裂分,可用作Boc-谷氨酸和天冬氨酸阴离子的手性溶解试剂,用于检测客体对映体纯度。3.合成了基于蒽和手性氨基酸的水溶性荧光受体Ⅲ-1、Ⅲ-2和Ⅲ-1-Cu2+,通过荧光滴定和圆二色谱研究了在水溶液中的主客体相互作用性质。通过非线性拟合,表明主客体形成1：1络合物。受体Ⅲ-1、Ⅲ-2表现出对Cu2+的高度选择性识别效果,受体对Cu2+的加入表现为灵敏的荧光猝灭现象,受体Ⅲ-1、Ⅲ-2可用作在水溶液中(pH7.4, Tris-HCl buffer)对二价铜离子的荧光探针。金属络合物受体Ⅲ-1-Cu2+对扁桃酸具有很好的手性识别能力,对L-构型的扁桃酸阴离子荧光增强响应要明显高于对D-构型扁桃酸阴离子,其对映选择性Kass(L)/Kass(D=15.2；通过非线性拟合,受体与L-,D-扁桃酸形成1：1络合物。通过圆二色谱测定,L-构型扁桃酸阴离子对受体Ⅲ-1-Cu2+构象的影响要大于D-扁桃酸阴离子,说明受体具有对L-构型扁桃酸阴离子更好的选择性识别能力。受体Ⅲ-1-Cu2+有望使用作为生理条件下对扁桃酸阴离子对映体的对映选择性的荧光化学传感器。4.合成了含蒽的多氮杂配体Ⅳ-1和Ⅳ-2,其中配体Ⅳ-2出对金属离子Cd2+、Zn2+、Cu2+表现出不同的荧光响应,可用作为金属离子光化学传感器。受体Ⅳ-1-Zn2+表现出对Pi和PPi阴离子灵敏的荧光猝灭现象,通过质谱和核磁研究了主客体相互作用过程,受体对PPi阴离子的络合常数要大于Pi。而络合物受体Ⅳ-2-Eu3+和Ⅳ-2-Tb3+在水溶液中表现出对PPi阴离子专一的的化学选择性,受体可以用作为水溶液中PPi阴离子PET荧光传感器。5.合成了两种金属络合物受体V-1-2Zn2+和V-1-2Cu2+,通过竞争取代机理检测了三元络合物主体Ⅴ-1-2Zn2+(PV)和Ⅴ-1-2Cu2+(PV)对客体阴离子的识别性能,紫外检测结果表明了主体Ⅴ-1-2Zn2+(PV)和Ⅴ-1-2Cu2+(PV)对PPi阴离子的优良的化学选择性识别,识别过程中表现出明显的肉眼可见的颜色变化,我们通过圆二色谱验证了主体对客体的选择性识别作用。这两种主体可以用作为生理pH条件下PPi阴离子的生色化学传感器。6.合成了手性配体Ⅵ-1和Ⅵ-2,通过与镧系金属Eu3+和Tb3+配位,生成了金属络合物主体Ⅵ-1-Tb3+,Ⅵ-2-Tb3+,Ⅵ-1-Eu3+,Ⅵ-2-Eu3+并将其用于阴离子的识别研究中。由于主体分子中的吡啶单元的光敏天线作用,通过激发吡啶单元(266nm),使激发态能量转移到金属f轨道激发态,发射出特征的金属荧光。在水溶液中,通过光谱变化研究了主体对客体阴离子的识别性质,发现这四种主体化合物均表现出对F-的荧光猝灭现象,而对其他阴离子的响应微弱,表现出对氟离子优良的化学选择性识别。更多还原

【Abstract】 Anions exist vastly in the nature and biosystem and play important roles in the maintaining of the humans and other organisms. Due to the importance of anions in pharmacy and biological science, the design and synthesis of efficient anion receptors attracts intensive interest of scientist and become a significant issue in the field of supramolucular chemistry. Compared with cation, anion has its own feature (larger dimension, complicated geometric structure and high hydration energy) that make the recognition of anions difficult and challenging.However, despite of these obvious difficulties, variety species of anion selective receptors have been developed in the recent years. Based on the theory of preorganization of the receptor and the complementary structure between the host and guest, the supramolecular complex was usually formed utilizing the hydrogen bonding, electrostatic interaction, hydrophobic effect or Van der Waals force. Receptors have optical response to anions make the anion sensing process much sensitive and convenient using the detection of UV-vis or fluorescent signals.Chiral recognition is one of the most fundamental and significant process in living system. The study of enantiometric recognition of biological important substrate is a very important research area since it can provide valuable information for understanding the mechanism of interaction in biological system, and for developing useful molecular devices in biochemical and pharmaceutical studies, catalysis and sensing.Many important biological anions existed in the aqueous solution, for many reported receptors, their binding ability to both chiral and achiral anion guest have been studied by 1H NMR, UV-vis spectra, fluorescence and electrochemical analysis. But most of the receptors are mainly studied in the organic solvent such as chloroform, CH3CN and DMSO. For the competing effect of the water, receptors of these kinds based on hydrogen bonding have little interaction with guests in the aqueous solution. The synthesis and study of water soluble receptor became a challenging work in the recent years.In this thesis, for the recognition of anions, a series of novel artificial receptors were synthesized, including four receptors based on thiourea and seven metal-ligand complex receptors. Their binging properties to anions (chiral dicarboxylates and biological important anions) were evaluated by UV-vis, fluorescence emission, 1HNMR, MS and circular dichlorisim methods.In charpter 1, describes the mechanism of the anion sensing and various types of anion receptors. Review the research progress of fluorescent and colorimetric anion receptors and their recognition abilities to anion guests.In charpter 2, through introduce the chial alanine, thiourea and signal units to the pyridine or benzyl skeleton, novel chiral receptorsⅡ-1、Ⅱ-2、Ⅱ-3、Ⅱ-4 were synthesized. Their discriminating abilities to chiral carboxylate anion enantiomers were examined by the UV-vis and fluorescent spectral and 1H NMR study. These receptors formed the 1:1 shoichiometriy complex with anion guests through the multiple hydrogen bonding interactions. PET sensorsⅡ-1 andⅡ-2 showed different fluorescence response to each anion enantiomers, and have certain chiral recognition abilities. For the electron-withdrawing effect of the p-nitrophenyl groups, the colorimetric sensorsⅡ-3 andⅡ-4 showed much stronger binding abilities to anion guests. Especially for the receptorⅡ-3, it shows a good recognition ability to mandelate and alanine anions, it can be used for discriminating these two chiral anions by the different colure changes. By split the Boc-NH signals of racemic glutamate and aspartate by 1H NMR, the receptorⅡ-3 can be used in the detecting the ee. value of these two anions.In charpter 3, two chiral fluorescent receptorsⅢ-1 andⅢ-2 were synthesized. ReceptorⅢ-1 andⅢ-2 showed a good selective binding ability to Cu2+. The hostⅢ-1-Cu2+ complex revealed an excellent enantioselective recognition ability to L-/D-mandelate anions in aqueous solution (Kass(L)/Kass(D)=15.2) and formed 1:1 stoichiometry complex. The obvious different changes in the fluorescence intensity of the interaction between theⅢ-1-Cu2+ and enantiomers of mandelate exhibited that hostⅢ-1-Cu2+ can be used as a good enantioselective fluorescent chemosensor for the chiral mandelate anions in the physiological pH condition.In chapter 4, two receptorsⅣ-1 andⅣ-2 were synthesized. Metal complexⅣ-1-Zn2+ showed good binding abilities to phosphate and pyrophosphate anions in aqueous solution and formed 1:1 stochiometric complex with anion guest. ReceptorⅣ-2 showed a selective recognition ability to metal ions such as Cd2+, Zn2+ and Cu2+ in aqueous solution with different fluorescent changes. The metal complex receptorsⅣ-2 -Eu3+ andⅣ-2-Tb3+ exhibited an excellent selective recognition ability and quenching response to the pyrophosphate anions (PPi) in the water solution (10mM HEPES buffer, H2O/MeOH=9:1). The better preorganization structure of the metal-complex receptorsⅣ-2-Eu3+ andⅣ-2-Tb3+, and larger charge density of anion guest may be responsible for the selective recognition of PPi anion. The good fluorescent response in the interaction between host and guest illustrate that these two receptors may be used as the fluorescent chemosensor for the PPi anion in the physiological pH condition.In charpter 5, two dinuclear metal complexⅤ-1-2Zn2+ andⅤ-1-2Cu2+ were synthesized and used as the receptor to anions. With the addition of equal amount of pyrocatechol violet (PV) as the indicator to theⅤ-1-2Zn2+ orⅤ-1-2Cu2+ solution, the complexⅤ-1-2Zn2+(PV) orⅤ-1-2Cu2+(PV) were formed with a dark blue color. While the pyrophosphate anion was added to the mixture, the color was changed to bright yellow, which indicate that PV was displaced by PPi from the ternary complex. The color of the complex was not changed when other anions were added even in the same amounts. It is clear that the pre-organized structure of the receptorsⅤ-1-2Zn2+ andⅤ-1-2Cu2+, and that the space complementary between receptor and anion guest resulted in the selective recognition for PPi. The obvious different changes of color and CD spectra indicated that two receptorsⅤ-1-2Zn2+ andⅤ-1-2Cu2+ may be used as efficient PPi sensors in aqueous solution.In charpter 6, the lanthanide metal complexesⅥ-1-Tb3+,Ⅵ-2-Tb3+,Ⅵ-1-Eu3+ andⅥ-2-Eu3+ were synthesized. Their recognition abilities to anion guests were examined by the lanthanide emission spectrum through the excitation of the pyridine unite of the ligand. Through the non-linear curve fitting, the receptor formed the 1:1 stoichiometry complex anion guest. These four receptors showed selectively fluorescent quenching to the fluoride anions in aqueous solution.更多还原