Department of Chemistry, Imperial College London, London SW7 2AZ, UK.
Inorg Chem. 2010 Sep 20;49(18):8371-80. doi: 10.1021/ic100884p.
Twelve mono- and dimetallic complexes (the metals being Cu(II), Pt(II), and Zn(II)) with terpyridine-based ligands have been prepared and fully characterized. The X-ray crystal structures of two of the complexes (monometallic Cu(II) and Zn(II) complexes with a morpholino-substituted terpyridine ligand) are reported. The affinities of the 12 complexes toward duplex and quadruplex (HTelo and c-myc) DNA have been investigated using a combination of techniques including fluorescent indicator displacement (FID) assay, UV-vis spectroscopy and circular dichroism (CD). These studies revealed that the dicopper and diplatinum complexes 11 and 12 bind very strongly to quadruplex DNA (up to K = 7.97 × 10(6) M(-1)) and with good selectivity (up to 100-fold) over duplex DNA. In these dimetallic complexes, one of the metals is coordinated to a terpyridine moiety yielding square based pyramidal (with Cu(II)) or square planar (with Pt(II)) geometries. The second metal is coordinated to a dipicolyl amine linked to terpyridine by a three-atom spacer. We propose that these complexes bind to quadruplex DNA via a combination of interactions: π-π end-stacking between the metal-terpyridine fragment and the guanine quartet, and electrostatic/metal-phosphate interactions (between the metal-dipicolyl amine fragment and DNA's backbone).
已制备并充分表征了 12 种基于三联吡啶的配体的单核和双核金属配合物（金属为 Cu(II)、Pt(II)和 Zn(II)）。报道了其中两种配合物（单核 Cu(II)和 Zn(II)配合物，配体为吗啉取代的三联吡啶）的 X 射线晶体结构。采用荧光指示剂置换（FID）测定、紫外-可见光谱和圆二色性（CD）等技术组合，研究了 12 种配合物与双链和四链（HTelo 和 c-myc）DNA 的亲和力。这些研究表明，二铜和二铂配合物 11 和 12 与四链 DNA 结合非常强（高达 K = 7.97 × 10(6) M(-1)），并且对双链 DNA 具有良好的选择性（高达 100 倍）。在这些双核配合物中，一个金属与三联吡啶部分配位，生成正方形基的三角锥形（Cu(II)）或正方形平面（Pt(II)）几何结构。第二个金属与通过三个原子间隔臂连接到三联吡啶的二吡啶甲酰胺配位。我们提出这些配合物通过多种相互作用与四链 DNA 结合：金属-三联吡啶片段与鸟嘌呤四重体之间的π-π末端堆积，以及静电/金属-磷酸盐相互作用（金属-二吡啶甲酰胺片段与 DNA 骨架之间）。
