Synthesis, Crystal Structures, Antibacterial Activity Studies Of Metal Complexes With Sulfachloropyridazine And Sulfamethoxine

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.