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二取代和三取代有机金属三蝶烯钯配合物与DNA的结合及相互作用

Binding and interaction of di- and tri-substituted organometallic triptycene palladium complexes with DNA.

作者信息

Kumari Rina, Bhowmick Sourav, Das Neeladri, Das Prolay

机构信息

Department of Chemistry, Indian Institute of Technology Patna, Patliputra Colony, Patna, 800013, Bihar, India.

出版信息

J Biol Inorg Chem. 2014 Oct;19(7):1221-32. doi: 10.1007/s00775-014-1180-z. Epub 2014 Jul 27.

Abstract

Two triptycene-based ligands with pendant bromophenyl units have been prepared. These triptycene derivatives have been used as synthons for the synthesis of di and tri nuclear palladium complexes. The organic molecules and their corresponding organometallic complexes have been fully characterized using nuclear magnetic resonance (NMR), infrared (IR) spectroscopy and mass spectrometry. The mode of binding and effect of the complexes on pUC19 plasmid, calf thymus DNA and oligomer duplex DNA have been investigated by a host of analytical methods. The complexes brought about unwinding of supercoiled plasmid and the unwinding angle was found to be related to the binding affinity of the complexes with DNA, where both these parameters were guided by the structure of the complexes. Concentration-dependent inhibition of endonuclease activity of SspI and BamHI by the complexes indicates preference for G/C sequence for binding to DNA. However, neither the complexes did not introduce any cleavage at abasic site in oligomer duplex DNA, nor they created linear form of the plasmid upon co-incubation with the DNA samples. The interactions of the complexes with DNA were found to be strongly guided by the structure of the complexes, where intercalation as well as groove binding was observed, without inflicting any damage to the DNA. The mode of interaction of the complexes with DNA was further confirmed by isothermal calorimetry.

摘要

已经制备了两种带有溴苯基侧基的三蝶烯基配体。这些三蝶烯衍生物已被用作合成双核和三核钯配合物的合成子。使用核磁共振(NMR)、红外(IR)光谱和质谱对有机分子及其相应的有机金属配合物进行了全面表征。通过一系列分析方法研究了配合物与pUC19质粒、小牛胸腺DNA和寡聚体双链DNA的结合模式及其影响。配合物导致超螺旋质粒解旋,并且发现解旋角度与配合物与DNA的结合亲和力有关,这两个参数均受配合物结构的指导。配合物对SspI和BamHI核酸内切酶活性的浓度依赖性抑制表明其对与DNA结合的G/C序列具有偏好性。然而,配合物既未在寡聚体双链DNA的无碱基位点引入任何切割,也未在与DNA样品共孵育时产生质粒的线性形式。发现配合物与DNA的相互作用受配合物结构的强烈指导,其中观察到了嵌入以及沟槽结合,而不会对DNA造成任何损伤。等温滴定量热法进一步证实了配合物与DNA的相互作用模式。

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