Studies On The Synthesis, Characterization And Bioactivities Of Metal Complexe With Pyrazoline-Enamine Derived From 4-Benzoyl-3-Methyl-1-Phenyl-2-Pyrazolin-5-One

As a typical β-diketone,4-benzoyl-3-methyl-1-phenyl-2-pyrazolin-5-one (HPMBP) could form a large number of complex with various metals or rare earth ions to be widely used as the extraction agent, fluorescent material intermediate. Meanwhile, it also could have condensation reactionin with active amino compound, then be coordination role with many transition metal ions, so that its biological activity was significantly enhanced, showing the broad-spectrum of antibacterial, antiviral and anti-tumor properties. In this paper, HPMBP as the forequarters material, 3 new pyrazoline-enamine and various new metal complexe are synthetized and a ligand crystal, two complex crystal are cultivated. These ligands and complexe are characterized using a combination of elemental analysis, IR spectrometry, UV-Vis spectrometry and conductivity meter to speculate the possible coordination sites composition and coordination modes. The single crystals are measured by X-ray single crystal diffraction. Fluorescence properties of ligands and their complexe are tested. Moreover, the mode of interaction between Zinc Schiff base complexe and CT-DNA is studied. Antitumor activity screening of the synthesized complexe is carried out using MTT method and the 26S protein activity inhibition by the copper and zinc complexe derived from HPMBP and 2-amino-5-methyl phenol is further explored. The main contents are as follows:(1) A series metal complexe derived from HPMBP and 4-Aminophenylacetic acid were synthetized. The chemical compositions of the ligand and complexe are determind to be C26H23N3O3 (HL1)�'�M(L1)2] (M=Cu(Ⅱ)、Zn(Ⅱ)、Mn(Ⅱ)、Cd(Ⅱ)、 Co(Ⅱ)、Ni(Ⅱ)). Ligand is pyrazoline-enamine structure. In the role of coordination process of ligands and the metal ions, H proton of C-NH occurs transferring so the carbonyl in a pyrazoline ring forms C-OH structure, while the corresponding C-N is converted into C=N double bond to form Schiff base complexe with metal ions by coordinated actionOne ligand crystal is obtained:HL1. The crystal crystallizes in the Triclinic system; space group P-1 with a=7.8603(10) A, b=11.0199(15) A, c=13.9938(17) A, a=107.838(12)°,β=100.159(11)°, γ=103.577(12)°, V=1080.5(2) A3, F(000)=448, Dc=1.049 g·cm-3,R1=0.0593,wR2=0.0906, ρ calcd 1.308 g·cm-3; Independent diffraction point is 3811. Two molecules of HL1 with pyrazoline-enamine structure are connected by hydrogen bonding to form a dimer. There are also intermolecular hydrogen bonding and C-H…π interaction; through which the adjacent dimers are connected to form a 1-D chain structure. The 1-D chains are further linked by the C-H…π interaction to give rise to a 2-D layer structure. Adjacent layers are connected through van der Waals forces to form the 3-D network.One complex crystal is obtained:[Zn(L1)2]. The crystal crystallizes in the Triclinic system; space group P-1, coordination mode of metal ions with ligand:metal ions coordinated with 4 atoms from two ligand, including N atoms in C=N by condensation and O atom in C-OH of proton transferring, forming distorted tetrahedral structure. The molecules of complex is further connected by hydrogen bonds, C-H…π interactions and van der Waals forces to give rise to a 3-D network. (2) A series of metal complexe derived from HPMBP and 4-aminobenzamide were synthetized. The chemical compositions of the ligand and complexe are determind to be C24H20N4O2 (HL2)�'�[M(L2)2(H2O)2] M=Cu(Ⅱ)、Zn(Ⅱ)、Mn(Ⅱ)、Cd(Ⅱ)、 Co(Ⅱ)、Ni(Ⅱ)). Ligand is pyrazoline-enamine structure. In the role of coordination process of ligands and the metal ions, H proton of C-NH occurs transferring to form Schiff base complexe with metal ions by coordinated action.One complex crystal is obtained:[Co(L2)2(H2O)2]. The crystal crystallizes in the Triclinic system, Six-coordinate distorted octahedral structure; space group P-1, coordination mode of metal ions with ligand:metal ions Co (Ⅱ)coordinated with 6 atoms from two ligand and two H2O, including N atoms in C=N by condensation, O atom in C-OH of proton transferring and in coordinated water molecules. Two molecules of complex are connected by C14-H14…O1 and C30-H30…O1 hydrogen bonds to form a dimer. The C42-H42B…N7 hydrogen bonding links the dimers to give rise to a 1-D chain structure. These chains are further connected by van der Waals forces to form the 3-D network.(3) A series of metal complexe derived from HPMBP and 2-amino-5-methyl phenol were synthetized. The chemical compositions of the ligand and complexe are determind to be C24H21N3O2 (H2L3) and [ML3(H2O)2] (M= Cu(Ⅱ)、Zn(Ⅱ)、Mn(Ⅱ)、 Cd(Ⅱ)、Co(Ⅱ)、Ni(Ⅱ)) by characterization. Ligand is pyrazoline-enamine structure. In the role of coordination process of ligands and the metal ions, H proton of C-NH occurs transferring to form Schiff base complexe with metal ions by coordinated action. Coordination mode of metal ions with ligand:metal ions coordinated with 5 atoms from two ligand, including N atoms in C=N by condensation, O atom in C-OH of proton transferring and in phenolic hydroxyl.(4) The fluorescence properties of ligands and part of their metal based complexe were studied, selecting fluorescent preferred complexe:[Zn(L’)2], [Cd(L’)2], [Co(L’)2], [Mn(L2)2(H2O)2], [Co(L2)2(H2O)2], [Ni(L2)2(H2O)2], [NiL3(H2O)2]. Compared to the corresponding ligands with weak fluorescence properties, maximum excitation and emission maximum peak position of the complexe shifted, fluorescence intensity significantly enhanced. This result is attributed to that after the ligand-metal complex in the dehydrogenation, the expansion of the conjugated system lead frontier orbital energy gap to narrowing.(5) The interaction between calf thymus DNA and the complexe [Zn(L’)2] (2b), [ZnL3(H2O)2] (4b)was investigated by UV-visible absorption spectra, fluorescence spectroscopy and other methods. The result shows that the complex most likely interacts with DNA in partially inserted role.(6) By exploring whether the five kinds of metal complexe [Zn(L1)2] (2b), [Co(L2)2(H2O)2] (3e), [CuL3(H2O)2] (4a), [ZnL3(H2O)2] (4b), [CdL3(H2O)2] (4c) have inhibitory effect for human breast cancer MDA-MB-231 cells malignant proliferation with MTT method, initially screeed complexe 4a and 4b which have the strong inhibition.A further study shows that the metal complexe have inhibition for 26S protein activity, and there was a significant positive correlation between rate and concentration.