【作者】 李彦萍；

【导师】 杨频；

【作者基本信息】 山西大学 ， 无机化学， 2007， 博士

【摘要】 咪唑具有特异的质子接受性能、共轭酸碱性能及识别配位性能，享有“生命配体”之美誉。在自然界中，咪唑作为酶的活性中心功能基团，参与了不少重要的生物化学反应，对生命活动起着十分重要的作用。而含有两个咪唑环的2，2′-联咪唑（H₂biim）是一个多质子给予双齿配体，可以与许多金属形成结构独特的配合物，是配位化学、超分子化学及其相关领域的重要研究对象之一；而且它还是一个重要的生物分子，在生物学上有非常广泛的用途，特别是在合成模拟酶方面。因此，一方面，研究联咪唑类金属配合物的结构及其与DNA之间的作用机理，进一步探讨小分子的结构与其生物活性之间的关系，不仅能帮助人们从分子水平理解人的生命过程及其某些疾病的发病机理，而且还为人们通过分子设计来寻求临床上更为有效的药物和开发出新一代高效的DNA结构探针提供理论指导；另一方面，研究联咪唑及其金属配合物的氢键组装对于构建超分子体系具有重要意义。本文首先合成了几个含联咪唑及其衍生物的金属配合物，用元素分析、红外光谱、晶体衍射等对其结构进行了表征，并用紫外、荧光、电化学、粘度、凝胶电泳等实验技术和分子模拟理论技术，研究了这些配合物与DNA之间的相互作用。其次，合成了五个联咪唑及其金属配合物与苯羧酸通过氢键组装的超分子化合物，研究了其中的多种氢键模式和π-π相互作用。主要的研究结果概括如下：1．合成了联咪唑锰配合物Mn（H₃biim）₂（NCS）₂Cl₂和联咪唑镉配合物Cd（H₃biim）₂（NCS）₂Cl₂，晶体结构表明这两个配合物结构相似，均为中性化合物，联咪唑的一个氮原子被质子化，形成一价阳离子（H₃biim⁺），它采取单齿配位，中心Mn（Cd）原子是六配位，其配位环境为畸变的八面体。摩尔电导实验和量化计算结果表明，它们在溶液中发生离解，形成配合物阳离子[Mn（H₃biim）₂（H₂O）₂]⁴⁺，[Cd（H₃biim）₂（H₂O）₂]⁴⁺。与DNA相互作用的实验表明，这两个配合物主要是在沟面与DNA发生静电结合。DNA对锰配合物、镉配合物的荧光有猝灭作用，从中得到配合物与DNA的结合常数分别为1.48×10⁴ L／mol（锰配合物）和1.98×10⁴ L／mol（镉配合物）。凝胶电泳实验表明锰配合物在pH=7.2、37℃条件下能够切割质粒pBR322 DNA，其表观速率常数为0.20h^-1，我们对其切割机理进行了初步探讨，推断其为水解切割；镉配合物也能在pH=7.2、37℃条件下切割质粒pBR322 DNA。合成了双甲基联咪唑双核铜（Ⅱ）配合物[Cu₂（Dmbiim）₄（H₂O）₂]（ClO₄）₄·6H₂O（Dmbiim，1，1′-二甲基-2，2′-联咪唑），晶体结构表明，整个分子呈笼状，两个铜原子由1，1′-二甲基-2，2′-联咪唑桥联，两个铜原子之间的距离为3.065A。整个分子形成了两个互相交叉的通道，这样的通道在超分子材料中有着非常重要的意义。研究了该配合物与DNA之间的相互作用，实验结果发现该配合物通过静电作用与小牛胸腺DNA的小沟键合。另外，凝胶电泳实验表明该配合物在抗坏血酸存在的情况下，能够在pH=8.0、37℃条件下有效切割质粒pBR322 DNA。2．利用2，2′-联咪唑与4-氨基苯甲酸（PABA），3，4，5-三羟基苯甲酸（THBA），磺基水杨酸（5-SSA）之间的氢键作用合成了三个超分子化合物：4-氨基苯甲酸-2，2′-联咪唑盐酸盐（Ⅰ），3，4，5-三羟基苯甲酸-2，2′-联咪唑盐（Ⅱ），磺基水杨酸-2，2′-联咪唑盐（Ⅲ）。由于联咪唑中的氮原子被质子化，化合物中存在着各种各样的氢键作用模式。在化合物（Ⅰ）中，晶体结构中的基本单元是一个通过氢键模式R₂²（9）和R₂¹（7）构成的氢键三聚体PABA…H₃biim⁺…Cl^-，这个三聚体基本单元又通过N-H…Cl氢键相互作用形成了一维带状结构。这个一维带状结构进一步通过带与带之间的N-H…O弱氢键、相邻苯环和咪唑环之间的π-π堆积作用形成了三维网状结构。在化合物（Ⅱ）中，晶体中的基本单元是一个通过氢键模式R₂²（9）构成的氢键三聚体THBA^-…H₄biim²⁺…THBA^-，这个三聚体单元又通过O-H…O氢键进一步延伸成了三维网状结构。相邻的苯环与咪唑环之间、苯环与苯环之间的π-π堆积作用进一步稳定了该化合物的三维网状结构。在化合物（Ⅲ）中，含有两个构型不同的联咪唑阳离子H₃biim⁺-1（N1，N2，N3，N4）和H₃biim⁺-2（N5，N6，N7，N8）。由于H₃biim⁺-1比H₃biim⁺-2扭曲的更厉害，两个相邻的H₃biim⁺-2通过R₂²（10）环氢键肩并肩地连接，形成了中心对称的二聚体：[H₃biim⁺-2…H₃biim⁺-2]；而两个相邻的H₃biim⁺-1形成了不对称的二聚体：[H₃biim⁺-1…H₃biim⁺-1]。同时，H₃biim+-1与相邻的5-SSA^2-通过R₂²（9）环氢键连接，而H₃biim⁺-2与相邻的5-SSA^2-通过R₂¹（7）环氢键连接。而且，水分子与5-SSA^2-中的磺酸基团之间存在着O-H…O氢键作用，晶体中还有弱的C-H…O氢键，咪唑环和苯环之间还存在着π-π堆积作用。这些作用力共同促成了该化合物的三维网状结构。还合成了联咪唑镍配合物[Ni（H₂biim）₂（PABA）₂]Cl₂·2H₂O（PABA，4-氨基苯甲酸）和联咪唑钴配合物[Co（H₂biim）₂（H₂O）₂]（isophthalate）·4H₂O（isophthalate，间苯二甲酸）。在镍配合物中，阳离子[Ni（H₂biim）₂（PABA）₂]²⁺，阴离子Cl^-和水分子通过N-H…Cl，O-H…Cl，O-H…O氢键相连形成二维网状结构，氢键模式为R₂¹（7）和R₄⁴（12）。该二维网状结构进一步通过相邻苯环之间的π-π堆积作用形成了层状结构。在钴配合物中，阳离子[Co（H₂biim）₂（OH₂）₂]²⁺与相邻的两个间苯二甲酸根阴离子通过环氢键R₂²（9）相连，形成一维链状结构。由于间苯二甲酸中的两个羧酸基团处于间位位置，使这个链呈现波浪式。水分子通过O-H…O氢键把链连接成了二维网状结构。相邻的咪唑环和苯环之间，咪唑环和咪唑环之间的π-π堆积作用进一步稳定了该配合物的二维网状结构。更多还原

【Abstract】 Imidazole, with the prestige of ’life ligand’, has distinguished talents of proton acceptor, conjugated acid-base and recognition ability for coordination. In nature, imidazole participates in many important biochemical reactions, acting as the functional group in enzymes’ active centers. 2,2’-biimidazole （Hzbiim）, as a bidentate chelating ligand with multi-proton donor sites, has two imidazole rings and can coordinate to many metals, forming complexes with particular structures. Therefore, it is one of the most important objects that interested in coordination chemistry, supramolecular chemistry and other related fields. At the same time, it is an important biological molecule that used abroad in biology, especially in enzyme mimics. Therefore, on the one hand, a more profound study on the mechanism of the interaction of the complexes involving H₂biim with DNA, and the relationships between the molecular structure and biological activity will not only help us to understand the process of life on a molecular level and pathogenic mechanism of some illness, but also provide rationales for new drug designs, as well as a means to develop novel agents for exploring the structures of nucleic acids. On the other hand, it is significant to study hydrogen-bonded assemblies involving H₂biim and its complexes to build supramolecular systemIn this thesis, firstly, we synthesized several metal complexes from H₂biim and its derivatives, characterized their structures with the methods of elemental analyses （EA）, IR and X-ray Crystallography. We also investigated the interaction between these complexes and DNA by using UV, fluorescent spectra, electrochemistry, viscosity measurements, gel electrophoresis and molecular modeling. Secondly, starting from H₂biim, we synthesized five supramolecular compounds assemblied through hydrogen-bonding, investigated the H-bonding patterns andπ-πinteractions. The main results include:1. Two complexes, i.e. Mn（H₃biim）₂（NCS）₂Cl₂ and Cd（H₃biim）₂（NCS）₂Cl₂ have been synthesized from H₂biim, their structures were determined by X-ray crystallography. The two complexes have similar structures and both are neutral compounds. One N atom in H₂biim is protonated, forming a H3biim+ cation. The later is an unidentate ligand, the central metal, Cd or Mn is six coordinated and adopts a distorted octahedral environment. Molar electrolytic conductivity and quantum chemistry calculations reveal that the two complexes are disociated in solution, forming the cations, [Mn（H₃biim）₂（H₂O）₂]⁴⁺ or [Cd（H₃biim）₂（H₂O）₂]⁴⁺. Investigations on the interaction between DNA and the complexes show that the binding mode of the two complexes with DNA is mainly electrostatic. We found that DNA can quench the fluorescence intensity of the complexes, and thus obtained their, binding constants to be 1.48×10⁴ L/mol for Mn（H₃biim）₂（NCS）₂Cl₂ and 1.98×10⁴ L/mol for Cd（H₃biim）₂（NCS）₂Cl₂, respectively. We also found that the complex [Mn（H₃biim）₂（NCS）₂Cl₂] can cleave plasmid pBR322 DNA at pH 7.2 and 37℃. Studies on the mechanism of DNA cleavage implicate that DNA cleavage mediated by [Mn（H₃biim）₂（NCS）₂Cl₂] occurs via a hydrolytic path. Also, the complex [Cd（H₃biim）₂（NCS）₂Cl₂] can cleave plasmid pBR322 DNA at pH 7.2 and 37℃.The binuclear copper（Ⅱ） complex with 1,1’-dimethyl-2,2’-biimidazole ligand, [Cu₂（Dmbiim）₄（H₂O）₂]（ClO₄）₄·6H₂O （Dmbiim=1,1’-dimethyl-2,2’-biimidazole） was synthesized and determined by X-ray crystallography. The crystal structure reveals that the complex is cage-shaped, with two Cu atoms bridged by Dmbiim. The distance between the two Cu atoms is 3.065A and two channels crossed each other were formed. Such type of channels would be significant in the field of supramolecuar material. DNA-binding investigations show that the copper（Ⅱ） complex interacts with DNA through minor groove binding. In addition, we found that the copper（Ⅱ） complex can cleave circular plasmid pBR322 DNA efficiently in the presence of AH₂ （ascorbic acid） at pH 8.0 and 37℃.2. Supramolecular assemblies of 2,2’-biimidazole with 4-aminobenzoic acid（PABA）, 3,4,5-trihydroxy benzoic acid（THBA） and 5-sulfosalicylic acid（5-S SA）, i.e. 2-（2-1H-imidazolyl）-1H-imidazolium chloride-4-aminobenzoic acid （Ⅰ）, 2,2’-bi-1H-imidazolium bis（3,4,5-trihydroxy benzoate） tetrahydrate （Ⅱ） and bis（2-（2-1H-imidazolyl）-1H-imidazolium） 3-carboxy-4-hydroxybenzene-sulfonate monohydrate （Ⅲ） have been synthesized and characterized by X-ray diffraction methods. Various H-bonds modes were found in these compounds owing to the protonization of N atoms in H₂biim. In compound （Ⅰ）, a fundamental unit of the crystal structure consisting a hydrogen-bonded trimer: PABA…H₃biim⁺…Cl^- via R₂² （9） and R₂¹ （7） forms a 1D ribbon through H-bond interactions. This 1D structure then extends into 3D via further H-bond andπ-πinteractions. In compound （Ⅱ）, a fundamental unit of crystal structure consists of a hydrogen-bonded trimer: THBA^-…H₄biim²⁺…THBA via R₂² （9）, which forms a 3D network by H-bonds. The 3D stacking is strengthened in further byπ-πinteractions between phenyl and adjacent imidazole rings, phenyl and phenyl rings. In compound （Ⅲ）, there are two different H₃biim⁺ （H₃biim⁺-1 involving N1, N2, N3, N4 and H_biim⁺-2 involving N5, N6, N7, N8）. Two adjacent H₃biim⁺-2 species connect each other by a direct side-by-side interaction, forming a centrosymmetric [H₃biim⁺-2…H₃biim⁺-2] dimer via R₂² （10）. While two adjacent H₃biim⁺-1 species connect each other, yielding an unsymmetrical [H₃biim+-1…H₃biim⁺-1] dimer via R₂² （10）, which maybe the result of the more contorted H₃biim⁺-1 than H₃biim⁺-2. In addition, the H₃biim⁺-1 cation and adjacent 5-SSA^2- anion species connect each other through cyclic R₂² （9） interaction, the H₃biim⁺-2 cation and adjacent 5-SSA^2- anion species connect each other through cyclic R₂² （7） interaction. And more, there exist some O—H…O hydrogen-bonds between water molecules and O atoms of sulfonate groups in 5-SSA^2-, weak C—H…O H-bonds and cation-anionπ-πstacking interactions in the compound. The overall interactions aforesaid result in the formation of the 3D network.Another two complexes, [Ni（H₂biim）₂（PABA）₂]Cl₂·2H₂O （PABA=4-aminobenzoic acid） and [Co（H_biim）₂（H₂O）₂]（isophthalate）·4H₂O, deriving from H₂biim, have been synthesized and characterized by. X-ray crystallography. In Ni（Ⅱ） complex, the cation [Ni（H₂biim）₂（PABA）₂]²⁺, Cl^- anion and H₂O molecule connects together via R₂¹（7） and R₄⁴（12）, forming 2D network. This network then forms to layer structure byπ-πinteractions between adjacent benzene rings. In Co（Ⅱ） complex, the cation [Co（H₂biim）₂（OH₂）₂]²⁺ connects with two isophthalate anions via R₂² （9）, forming a 1D-extended chain. The relative position of the carboxylate groups confers a wavy form to the 1D-array. This 1D structure then extends into 2D network structure via further O—H…O H-bonds andπ-πinteractions between imidazole and adjacent phenyl rings, imidazole and imidazole rings.更多还原