Mixed-Ligand Copper(II) Maltolate Complexes: Synthesis, Characterization, DNA Binding and Cleavage, and Cytotoxicity
Mixed-Ligand Copper(II) Maltolate Complexes: Synthesis, Characterization, DNA Binding and Cleavage, and Cytotoxicity
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DOI：
10.1021/ic9004642
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发表时间：
2009-10-05
影响因子：
4.6
通讯作者：
Joshi, Rajendra
中科院分区：
文献类型：
--
作者：
Barve, Archika;Kumbhar, Avinash;Joshi, Rajendra
混合配体配合物[Cu(L)(maltol)]，其中L = 2,2'-联吡啶（bpy; 1）， 1,10-菲罗啉（phen; 2）， 1,10-菲罗啉-5,6-二酮（phendione; 3），二吡啶[3,2-a:2',3'-c]吩那嗪（dppz; 4），和4b，5,7,7a-四氢-4b，7a-亚胺-甲烷-亚胺- 6h -咪唑[4,5-f][1,10]-菲罗啉-6,13-二酮(联吡啶基糖基脲；bpg；1、2和5的单晶x射线结构呈扭曲的方锥体结构，多吡啶配体和麦芽糖醇占据赤道位置，水或硝酸盐阴离子占据轴向位置。配合物的N，N-二甲基甲酰胺玻璃和单晶电子顺磁共振证实了其扭曲的方锥体结构。采用不同的技术（吸收滴定法、粘度法、热熔法和荧光猝灭法）研究DNA结合表明，平面多吡啶基配体部分嵌入DNA。该复合物通过水解机制切割质粒pBR322 DNA。本文还详细介绍了假Michaelis-Menten和真Michaelis-Menten条件下的DNA裂解动力学，以及4-硝基苯基磷酸模型下的磷酸二酯酶活性。复合物对宫颈癌细胞系的细胞毒性表明，金属和配体之间的协同作用显著增强了细胞死亡，IC50类似于150-270 μ g mL（-1）。
The mixed-ligand complexes [Cu(L)(maltol)] where L = 2,2'-bipyridine (bpy; 1), 1,10-phenanthroline (phen; 2), 1,10-phenanthroline-5,6-dione (phendione; 3), dipyrido[3,2-a:2',3'-c]phenazine (dppz; 4), and 4b,5,7,7a-tetrahydro-4b,7a-epiminomethanoimino-6H-imidazo[4,5-f][1,10]-phenanthroline-6,13-dione (bipyridylglycoluril; bpg; 5) have been synthesized and characterized by structural, analytical, and spectral methods, The single-crystal X-ray structures of 1, 2, and 5 exhibit a distorted square-pyramidal structure, with the polypyridyl ligands and maltol occupying equatorial positions and either a water or nitrate anion at the axial position. The N,N-dimethylformamide glass as well as the single-crystal electron paramagnetic resonance of the complexes confirms the distorted square-pyramidal structure. The DNA binding investigated using different techniques (absorption titration, viscosity, thermal melting, and fluorescence quenching) indicates the partial intercalation of the planar polypyridyl ligands into DNA. The complexes cleave plasmid pBR322 DNA by a hydrolytic mechanism. The kinetic aspects of DNA cleavage under pseudoMichaelis-Menten and true Michaelis-Menten conditions as well as the phosphodiesterase activity using model 4-nitrophenylphosphate are also detailed. The cytotoxicity of the complexes against HeLa (cervical) cancer cell lines shows that synergy between the metal and ligands results in a significant enhancement in the cell death with IC50 of similar to 150-270 mu g mL(-1).