Uma Maheswari P, Palaniandavar M
Department of Chemistry, Bharathidasan University, Tiruchirappalli 620 024, Tamilnadu, India.
J Inorg Biochem. 2004 Feb;98(2):219-30. doi: 10.1016/j.jinorgbio.2003.09.003.
A series of ruthenium(II) mixed ligand complexes of the type Ru(NH(3))(4)(L), where L=imidazo[4,5-f][1,10]phenanthroline (ip), 2-phenylimidazo[4,5-f][1,10]phenanthroline (pip), 2-(2-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline (hpip), 4,7-diphenyl-1,10-phenanthroline (dip), naphtha[2,3-a]dipyrido[3,2-h:2',3'-f]phenazine-5,18-dione (qdppz), 5,18-dihydroxynaphtho[2,3-a]dipyrido[3,2-H:2',3'-f]phenazine (hqdppz), have been isolated and characterized. The interaction of these complexes with calf thymus DNA (CT DNA) has been explored by using absorption, emission, and circular dichroic spectral methods, thermal denaturation studies and viscometry. All these studies suggest the involvement of the modified phenanthroline 'face' rather than the ammonia 'face' of the complexes in DNA binding. An intercalative mode of DNA binding, which involves the insertion of the modified phenanthroline ligands in between the base pairs, is suggested. The results from absorption spectral titration and circular dichroism (CD), thermal denaturation and viscosity experiments indicate that the qdppz and hqdppz complexes (K(b) approximately 10(6) and Delta T(m)=11-13 degrees C) bind more avidly than the ip, pip and hpip complexes (K(b) approximately 10(5), Delta T(m)=6-8 degrees C). Intramolecular hydrogen bonding in the hpip and hqdppz complexes increases the surface area of the intercalating diimines and enhances the DNA binding affinity substantially. The ammonia co-ligands of the complexes are possibly involved in hydrogen bonding with the intrastrand nucleobases to favour intercalation of the extended aromatic ligands. Circular dichroism spectral studies reveal that all the complexes effect certain structural changes on DNA duplex; Ru(NH(3))(4)(ip) induces a B to A transition while Ru(NH(3))(4)(qdppz) a B to Psi conformational change on CT DNA. Cleavage efficiency of the complexes were determined using pBR322 supercoiled plasmid DNA. All the complexes, except hqdppz complex, promote the cleavage of supercoiled plasmid (form I) to relaxed circular form (form II).
已分离并表征了一系列通式为[Ru(NH₃)₄(L)]²⁺的钌(II)混合配体配合物，其中L = 咪唑并[4,5 - f][1,10]菲咯啉(ip)、2 - 苯基咪唑并[4,5 - f][1,10]菲咯啉(pip)、2 - (2 - 羟基苯基)咪唑并[4,5 - f][1,10]菲咯啉(hpip)、4,7 - 二苯基 - 1,10 - 菲咯啉(dip)、萘并[2,3 - a]二吡啶并[3,2 - h:2',3' - f]吩嗪 - 5,18 - 二酮(qdppz)、5,18 - 二羟基萘并[2,3 - a]二吡啶并[3,2 - H:2',3' - f]吩嗪(hqdppz)。通过吸收光谱、发射光谱、圆二色光谱法、热变性研究和粘度测定等方法，探索了这些配合物与小牛胸腺DNA(CT DNA)的相互作用。所有这些研究表明，在DNA结合过程中，配合物中经过修饰的菲咯啉“面”而非氨“面”参与其中。推测存在一种插入式的DNA结合模式，即修饰的菲咯啉配体插入碱基对之间。吸收光谱滴定、圆二色性(CD)、热变性和粘度实验结果表明，qdppz和hqdppz配合物(Kb约为10⁶，ΔTm = 11 - 13℃)比ip、pip和hpip配合物(Kb约为10⁵，ΔTm = 6 - 8℃)结合得更紧密。hpip和hqdppz配合物中的分子内氢键增加了插入二亚胺的表面积，并显著增强了DNA结合亲和力。配合物中的氨共配体可能参与了与链内核碱基的氢键形成，以利于扩展芳香配体的插入。圆二色光谱研究表明，所有配合物都会使DNA双链发生一定的结构变化；[Ru(NH₃)₄(ip)]²⁺在CT DNA上诱导B型向A型转变，而[Ru(NH₃)₄(qdppz)]²⁺诱导B型向Ψ型构象变化。使用pBR322超螺旋质粒DNA测定配合物的切割效率。除hqdppz配合物外，所有配合物都能促进超螺旋质粒(形式I)切割为松弛环状形式(形式II)。
