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DNA binding by a new metallointercalator that contains a proflavine group bearing a hanging chelating unit

机译:新型金属嵌入剂与DNA结合,该金属嵌入剂包含带有悬垂螯合单元的黄酮基

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The new bifunctional molecule 3,6-diamine-9-[6,6-bis(2-aminoethyl) -1,6-diaminohexyl]acridine (D), which is characterised by both an aromatic moiety and a separate metal-complexing polyamine centre, has been synthesised. The characteristics of D and its Zn-II complex ([ZnD]) (protonation and metal-complexing constants, optical properties and self-aggregation phenomena) have been analysed by means of NMR spectroscopy, potentiometric, spectrophotometric and spectrofluorimetric techniques. The equilibria and kinetics of the binding process of D and [ZnD] to calf thymus DNA have been investigated at I=0.11M (NaCl) and 298.1 K by using spectroscopic methods and the stopped-flow technique. Static measurements show biphasic behaviour for both D-DNA and [ZnD]-DNA systems; this reveals the occurrence of two different binding processes depending on the polymer-to-dye molar ratio (P/D). The binding mode that occurs at low P/D values is interpreted in terms of external binding with a notable contribution from the polyamine residue. The binding mode at high P/D values corresponds to intercalation of the proflavine residue. Stopped-flow, circular dichroism and supercoiled-DNA unwinding experiments corroborate the proposed mechanism. Molecular-modelling studies support the intercalative process and evidence the influence of NH+center dot center dot center dot O interactions between the protonated acridine nitrogen atom and the oxygen atoms of the polyanion; these interactions play a key role in determining the conformation of DNA adducts.
机译:新的双功能分子3,6-二胺-9- [6,6-双(2-氨基乙基)-1,6-二氨基己基] ac啶(D),其特征在于既有芳族部分又有独立的金属络合多胺中心,已经综合。 D的特征及其Zn-II络合物([ZnD])(质子和金属络合物常数,光学性质和自聚集现象)已通过NMR光谱,电位法,分光光度法和荧光光谱法进行了分析。利用分光光度法和停止流技术,研究了D和[ZnD]与小牛胸腺DNA结合过程的平衡和动力学,反应条件为I = 0.11M(NaCl)和298.1K。静态测量显示D-DNA和[ZnD] -DNA系统的双相行为。这揭示了取决于聚合物与染料的摩尔比(P / D)的两种不同的结合过程的发生。在低P / D值下发生的结合模式是根据外部结合来解释的,其中多胺残基的贡献很大。在高P / D值下的结合模式对应于前黄素残基的插入。停止流,圆二色性和超螺旋DNA展开实验证实了所提出的机理。分子模型研究支持插层过程,并证明了质子化a啶氮原子和聚阴离子的氧原子之间的NH +中心点中心点中心点O相互作用的影响。这些相互作用在确定DNA加合物的构象中起关键作用。

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