【作者】 张运良；

【导师】 陈振锋；

【作者基本信息】 广西师范大学 ， 无机化学， 2007， 硕士

【摘要】 磺胺类药物因其抗菌谱广,性质稳定,使用方便,价格低廉特别是近来其增效剂的发现和配合使用,进一步稳固了其抗感染药物的地位,使磺胺类药物在临床上仍占据重要位置。磺胺类药物具有抑菌性能,其药理活性与金属离子形成配合物后通常得到明显加强。如磺胺嘧啶与银的配合物治疗典型的烫伤和烧伤有更佳的疗效。磺胺嘧啶与锌的配合物能阻止烫伤和烧伤中细菌感染。它们的疗效并不仅仅依靠金属离子[Ag(Ⅰ)或Zn(Ⅱ)缓慢释放],而是主要依靠金属离子所键合点的性质。磺胺类药物分子有多个配位点,可以采取单齿、螯合双齿和螯合桥联三齿等形成单核或多核配合物,还能形成配位聚合物,可能获得具有潜在应用前景的分子基材料。本文对磺胺类配合物的研究进行了综述。并以两种磺胺氯哒酮(H-L1)、磺胺二甲氧基嘧啶(H-L2)为主配体,合成了16个未见报道的新配合物,用元素分析、红外光谱、TG和X-单晶衍射等手段对之进行了表征,系统研究了它们的结构特点、热稳定性等性质;对配合物1、6、8还研究了它们与ct-DNA作用的键合模式,实验数据表明它们都与ct-DNA有较强的作用,有一定的研究价值。对配合物1～10、12～13还做了抗菌活性测试,结果表明配合物1、4、5、6、8、13具有抑菌活性,是潜在的治疗药物。本论文分为五个部分:第一章:用磺胺氯哒酮(H-L1)与锰、钴、镉、锌、铜盐及辅助配体[2,2’-联吡啶(2,2’-bipy)或1,10-啉菲啰啉(1,10-phen)]在溶剂热条件下反应得到7个单核配合物[Mn(L1)2(phen)] 1、[Mn(L1)2(2,2-bipy)] 2、[Co(L1)2(2,2-bipy)] 3、[Cd(L1)2(phen)] 4、[Zn(L1)2(2,2’-bipy)] 5、[Cu(L1)(phen)2](ClO4)·py 6、[Cu(L1)2(H2O)2] 7。配合物1～5均属三斜晶系,空间群P-1。配合物6～7均属单斜晶系,空间群P2(1)/n。配合物1～4的结构相似,中心离子M[M=Mn(II)、Co(II)、Cd(II)]的配位数都是六, M均为少见的稍畸变的三棱柱配位构型。L1及辅助配体均采取螯合双齿配位方式与中心金属配位。配合物5～6的中心金属[M=Zn(II)、Cu(II)]均为五配位的四方锥几何构型。配合物5和6中L1分别采取螯合双齿、磺酰胺氮和杂环氮单齿配位方式与配位。配合物7的中心金属铜采取四配位平面四边形构型。L1采取杂环氮单齿配位方式。配合物1～7中均存在较丰富的氢键,这些氢键将分子连接起来形成二维网状结构;同时存在π···π堆积作用,这些氢键作用和π···π堆积作用将配合物连接成三维网络结构。另外还测定了配合物1～7的抗菌活性以及配合物1、6与ct-DNA作用的紫外-可见光谱,研究表明配合物1、4、5、6具有一定抑菌活性,与ct-DNA有较强的作用且可能以插入方式与ct-DNA键合。第二章:磺胺氯哒酮(H-L1)与锰盐、铅盐及phen在溶剂热条件下反应得到配合物[Mn(phen)2Cl2](H-L1)2·H2O 8、[Mn(py)2(H2O)4](L1)2 9和[Pb2(phen)4Cl2](L1)2 10。配合物8～10均属单斜晶系,空间群P2(1)/c。配合物8～10的L1均以游离的形式存在。配合物(8)中心金属离子Mn(II)为六配位畸变八面体几何构型;配合物9由阳离子[Mn(py)2(H2O)4]2+和阴离子L1构成。中心离子Mn(II)为六配位的变形的八面体几何构型;配合物10由配阳离子[Pb2(phen)4Cl2]2+和配阴离子L1构成。双核配阳离子单元中Pb(II)分别与两个phen的4个氮原子及两个μ2-Cl-配位形成六配位(PbN4Cl2)畸变的八面体构型存在。而若把Pb(1)-O的键长限定不同则可从六配位的半球模式转化到八配位的全球模式。另外还测定了配合物8～10的抗菌活性以及配合物8与ct-DNA作用的紫外-可见、荧光光谱,研究表明配合物8～10具有一定抑菌活性,配合物8与ct-DNA可能以插入方式与ct-DNA键合。第三章:磺胺氯哒酮(H-L1)与镍盐、钴盐及phen在溶剂热条件下反应,得到配合物[Ni(L1)2(phen)][Ni(L1)(phen)2]NO3·CH3OH 11、[Co(L1)2(phen)][Co(L1)(phen)2]ClO4·C2H5OH 12。配合物11～12均属于三斜晶系,空间群为P-1。配合物11存在两种不同配位环境的镍中心。均为六配位拉长的八面体构型。配合物通过氢键和π···π堆积作用形成二维超分子结构。结构解析表明配合物12与配合物11具有相似的结构。另外还测定了配合物12的抗菌活性,结果表明配合物12对一些菌具有一定的抗菌活性。第四章:磺胺氯哒酮(H-L1)、AgNO3和4,4’-bipy在水热条件下反应得到配位聚合物[Ag2(L1)2]n 13。配合物13属单斜晶系,空间群P2(1)/n。配合物13中三个配体桥联两个Ag(I) [Ag(1)、Ag(2)],即通过L1上的杂环氮和磺酰胺氮分别连接,形成五元环结构Ag2N2C。每个银离子分别与两个配体上磺胺基上的N和嘧啶环上的N配位,形成两配位的直线形结构。L1采取桥联双齿配位方式参与配位,形成直线型一维无限链状配位聚合物。配合物中存在着Ag…Ag弱相互作用。配合物通过分子间、分子内氢键N-H…O、N-H…N使分子形成二维网络结构。第五章:磺胺二甲氧基嘧啶(H-L2)、4,4’-bipy分别与镍盐、铜盐在溶剂热条件下,得到配合物{Ni[(L2)(4,4-bipy)(NO3)]}n 14、{Cu[(L2)2(4,4-bipy)]·3H2O}n 15。H-L2与CoCl2·6H2O在溶剂热条件下,得到{[Co(L2)2]·CH3OH}n 16。配合物(14)～(16)均属单斜晶系,空间群分别为P2(1)/n、P2/n、P2(1)/n。在配合物(14)的中心金属Ni(II)为六配位的稍畸变的八面体配位构型。整个配合物以4,4’-bipy桥联形成无限“之”字形一维链状配位聚合物。在配合物15中,中心金属离子Cu(II)为四配位的平面四边形配位构型,整个配合物以4,4’-bipy桥联形成无限一维链状结构。在配合物16中心金属离子Co(II)配位数为六。配合物通过L2桥联成二维孔洞网状结构。在配合物14～16中L2分别采取螯合双齿、磺酰胺氮单齿、螯合桥联三齿配位方式参与配位。配合物14～16通过分子间、分子内氢键O-H…N、O-H…O、N-H…O使分子形成二维网络结构。更多还原

【Abstract】 Because sulfamide interesting structural characteristic and broad antibacterial spectrum, convenient application and lower price, the researches on sulfanilamide drug metal complexes have received much attention. Sulfamide drug are a type of effective chemotherapeutic agents for prevention and cure of bacterial infections in humans. Although the antibacterial activity sulfamides is related to the inhibition of the bacterial enzyme DHPS which catalyses the incorporation of p-aminobenzoic acid into the precursor of folic acid, the pharmacological activity of these agents is enhanced by complexation with metal ions. For example, rapid healing of skin disorders has been promoted by silver–sulfadiazine complex in human wound and topical burn therapy, and zinc–sulfadiazine complex in the prevention of bacterial infection in burned animals, in which the effectiveness of these burn treatment compounds solely depends on the presence of a metal ion [slow release of the Ag(I) or Zn(II)], but also strongly on the nature of the ligand binding bites to which the metal ion is bound. Through investigating the coordination chemistry of biological relevant ligands, it can confirm the binding site of metal and drug molecules, or(rather) the activity centers of drug molecules. On the other hand, we can expect to obtain the metal complexes with potential application. Therefore, it is important to study on the coordination modes of these sulf-drugs with metal ions, or the sulfanilamide drugs how to coordinate to metal ions under different conditions. In this paper, we report the synthesis, X-ray crystal structures, spectroscopic characterization, thermogravimetric analysis of 16 new metal complexes with sulfachloropyridazine (H-L1) and sulfamethoxine (H-L2). The antibacterial activity of complexes of 1～10 and 12～13 were assayed. The results show that some of these complexes such as 1, 4, 5, 6, 8 and 13, exhibit good antiviral activity with potential application. The interactions of 1 and 6 with ct-DNA are also characterized by UV-Vis, fluorescence, and their binding constants and modes to ct-DNA have been revealed. The results indicate that they are bonded strongly to ct-DNA, which is agree well with their antibacterial activity.Chapter One: Seven complexes [Mn(L1)2(phen)] 1, [Mn(L1)2(2,2-bipy)] 2, [Co(L1)2 (2,2-bipy)] 3, [Cd(L1)2(phen)] 4, [Zn(L1)2(2,2-bipy)] 5, [Cu(H-L1)2(phen)](ClO4)2·py 6 and [Cu(L1)2(H2O)2] 7 have been synthesized by the reaction of sulfachloropyridazine (H-L1), 2,2’-bidy or phen with Mn(II) or Co(II) or Cd(II) or Zn(II) salt and under the hydro(solv) thermal condition, respectively. Complexes 1～5 all belong to triclinic crystal system, space group P–1. Complexes 6, 7 crystallize in the monoclinic crystal system with space group P2(1)/n. The X-ray crystallographic analysis indicate that the structure of complexes 1～4 are similar. All central M [M=Mn(II), Co(II), Cd(II)] ions adopt six-coordinated slightly distorted triangular prismatic geometry. L1 and the second ligand adopt chelating bidentate coordination mode to participate in coordination. The central M [M=Zn(II),Cu(II)] ions in 5, 6 adopt a five-coordinated slightly distorted geometry. The sulfachloropyridazine bound to the metal ion in 5 with two coordinated modes: the monodentate and bidentate, but monodentate for 6. The metal Cu(II) in 7 adopts four-coordinated quadrilateral geometry with donor set N2O2, two heterocyclic N atoms from two sulfachloropyridazine and two O atoms from two water molecules. Complexes 1～7 are connected to 2D or 3D network via complicated hydrogen bonds andπ···πinteractions. In addition, the antibacterial activity assay results for 1 to 7 show that 1, 4, 5, 6 display considerable activity. The interactions of complex 1, 6 with ct-DNA were investigated by UV-Vis, fluorescence spectra, and illuminated that they interacted with ct-DNA with insert binding mode and presented strong binding interaction.Chapter Two: Three complexes [Mn(phen)2Cl2](H-L1)2·H2O 8,[Mn(py)2(H2O)4](L1)2 9 and [Pb2(phen)4Cl2](L1)2 10 have been synthesized through the reaction of sulfachloropyridazine (H-L1), Py or phen, and Mn(II) salt or Pb(II) salt under hydro(solv) thermal condition. 8～10 all crystallize in the monoclinic crystal system with space group P2(1)/c . The X-ray crystallographic analysis indicate that the structure of 8～10 are similar. L1 is free and does not participate in coordination in 8～10. The Mn(II) ion in 8, 9 both adopt six-coordinated distorted octahedral geometry. 8 and 9 are consist of [Mn(phen)2Cl2] and H-L1, [Mn(py)2(H2O)4]2+ and two L1, respectively. While 10 consists of [Pb2(phen)4(Cl)2]2+ and two L1. The two Pb(II) ions in 10 both adopt six-coordinated distorted octahedral geometry connected by bridgingμ2-Cl. Regarding the limit of Pb(1)-O bond distance, the central Pb(II) ion adopts half ball mode with six-coordinated to ball mode with coordinating to eight atoms. Complexes 8～10 are connected to 2D network via complicated hydrogen bonds andπ···πinteractions. At the same time, the antibacterial activity assay results for 8 to 10 show that 8 exhibit good antiviral. The interactions of complex 8 with ct-DNA were investigated by UV-Vis, fluorescence spectra, and indicated that they interacted with ct-DNA with insert binding mode and presented strong binding interaction.Chapter Three: The two complexes [Ni(L1)2(phen)][Ni(L1)(phen)2]NO3·CH3OH 11、[Co(L1)2(phen)][Co(L1)(phen)2]ClO4·C2H5OH 12 have been prepared by the reaction of H-L1, phen and Ni(II) or Co(II) salt and under the hydro(solv) thermal condition. They both belong to triclinic crystal system with space group P–1. In complex 11, there exist two independent six-coordinated nickel(II). The central Ni(II) ion both can be described as a distorted octahedral geometry. Each L1 adopts chelating bidentate coordination mode to form two five-membered chelating rings. The molecules connect to two-dimensional network via complex hydrogen bonds andπ···πinteractions. The X-ray crystallographic analysis indicates that structure of 12 is similar to 11. And the antibacterial activity assay results for 12 indicate that it have some activity.Chapter Four: The polymeric complex [Ag2(L1)2]n 13 has been synthesized by reacting AgNO3 and 4,4’-bipy with H-L1 respectively under the hydro(solv)thermal condition. X-ray single diffraction analysis of 13 indicates that 13 belongs to monoclinic crystal system with space group P2(1)/n. In the unit of complex 13, there are two independent Ag(I) ions coordinated by three L1 with two–coordinated linear geometry. Each L1 adopts bridging bidentate coordination mode connected adjacent silver(I) into an infinite 1D chain. The separation of Ag…Ag is 2.893(2)? implying strong metal-metal interaction. The adjacent infinite chains are connected by abundant intermolecular hydrogen bonds involving O-H…N, N-H…O and N-H…S into a three-dimensional network. The antibacterial activity assay results for 13 indicate that 12 have some activity.Chapter Five: The polymeric complexes [Ni(L2)(4,4-bipy)(NO3)n] 14,{[Cu(L2)2(4,4-bipy)]·3H2O}n 15 have been synthesized by the reaction of sulfamethoxine (H-L2), 4,4’-bipy, and Ni (II) salt or Cu(II) salt and under the hydro(solv) thermal condition. But {[Co(L2)2]·CH3OH}n 16 has been obtained by the reaction of H-L2 and CoCl2·6H2O. They all belong to monoclinic crystal system with space group P2(1)/n, P2/n, P2(1)/n, respectively. In 14, the geometry around the Ni(II) ion adopts six-coordinated distorted octahedral geometry. 14 is an infinite one-dimensional“zigzig”chain formed by a repeating mononuclear structural unit bridged by 4,4-bipy. In complex 15, the Cu(II) adopts four-coordinated quadrilateral geometry, forming an infinite one-dimensional chain by a repeating mononuclear structural unit bridged by 4,4’-bipy. However the Co(II) in complex 16 adopts a six-coordinated heavily distorted octahedral geometry, being coordinated to the sulfonamide N and the heterocyclic N of two bidentate sulfadimethoxine ligands generating two four-membered rings and two terminal amino of the other two L2 which are bonded to two adjacent cobalt(II) to complete the coordination sphere. Thus a 2D infinite network of 16 is formed through L2 linkage. In complexes 14～16, L2 adopts chelating bidentate, monodentate, chelating bridging tridentate coordination mode to participates in coordination, respectively.更多还原