Zhang Hang, Liu Chun-Sen, Bu Xian-He, Yang Ming
National Research Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, P.O. Box 261, Beijing 100083, PR China.
J Inorg Biochem. 2005 May;99(5):1119-25. doi: 10.1016/j.jinorgbio.2005.02.005.
A new ligand L, 1-[3-(2-pyridyl)pyrazol-1-ylmethyl]naphthalene, and its two metal complexes, Cu(L)32 (1) and Zn(L)32(H2O)2 (2), have been synthesized and characterized. The crystal structure of complex 1 was determined by single crystal X-ray diffraction, which crystallized in monoclinic, space group P2(1)/n with unit cell parameters, a = 12.710(4) angstroms, b = 12.135(3) angstroms, c = 33.450(9) angstroms, beta = 93.281(5) degrees and Z = 4. The Cu atom was six-coordinated to N(1), N(2), N(4), N(5), N(7) and N(8) from three L ligands and formed a slightly distorted octahedral geometry. Complexes 1 and 2, and ligand L were subjected to biological tests in vitro using three different cancer cell lines (HL-60, BGC-823 and MDA-MB-435). Complex 1 showed significant cytotoxic activity against three cancer cell lines. The interactions of complexes 1 and 2, and ligand L with calf thymus DNA were then investigated by thermal denaturation, viscosity measurements and spectrophotometric methods. The experimental results indicated that complexes 1 and 2 bound to DNA by intercalative mode via the ligand L. The intrinsic binding constants of complexes 1 and 2, and ligand L with DNA were 1.8 x 10(4), 5.4 x 10(3) and 2.76 x 10(3) M(-1), respectively.
一种新型配体L，即1-[3-(2-吡啶基)吡唑-1-基甲基]萘，及其两种金属配合物Cu(L)32 (1)和Zn(L)32(H2O)2 (2)已被合成并表征。配合物1的晶体结构通过单晶X射线衍射确定，其晶体属于单斜晶系，空间群为P2(1)/n，晶胞参数为：a = 12.710(4)埃，b = 12.135(3)埃，c = 33.450(9)埃，β = 93.281(5)°，Z = 4。铜原子与来自三个L配体的N(1)、N(2)、N(4)、N(5)、N(7)和N(8)形成六配位，构成略微扭曲的八面体几何构型。配合物1和2以及配体L使用三种不同的癌细胞系(HL-60、BGC-823和MDA-MB-435)进行了体外生物学测试。配合物1对三种癌细胞系显示出显著的细胞毒性活性。然后通过热变性、粘度测量和分光光度法研究了配合物1和2以及配体L与小牛胸腺DNA的相互作用。实验结果表明，配合物1和2通过配体L以插入模式与DNA结合。配合物1和2以及配体L与DNA的固有结合常数分别为1.8×10(4)、5.4×10(3)和2.76×10(3) M(-1)。
