School of Chemistry and Molecular Bioscience, University of Wollongong, Northfields Avenue, Wollongong 2522, Australia.
Research School of Chemistry, Australian National University, Canberra, Australian Capital Territory 0200, Australia.
Dalton Trans. 2020 Aug 4;49(30):10360-10379. doi: 10.1039/d0dt01370f.
A series of novel isomeric nickel Schiff base complexes, as well as nickel complexes of related ligands having asymmetric structures have been prepared and characterised using microanalysis, 1H and 13C NMR spectroscopy and ESI-MS. The Schiff base ligands were prepared by condensation reactions involving ethylenediamine and different derivatives of benzophenone. The solid-state structures of eight of the complexes were also determined and revealed that each possessed a regular square planar coordination geometry around the metal ion. Many of the new complexes featured at least one, and in many instances two, protonatable pendant groups that enhance aqueous solubility. This enabled the DNA binding properties of the latter complexes to be explored using a variety of instrumental approaches, including ESI-MS, circular dichroism (CD) spectroscopy, FRET melting assays and FID assays, as well as molecular docking studies. The results of experiments performed using ESI-MS suggested that none of the nickel complexes exhibit a high affinity towards either a double stranded DNA (dsDNA) molecule D2, or the parallel unimolecular quadruplex DNA (qDNA) molecule Q1. In contrast, complexes (8) and (12) both gave spectra which reflected a significant level of binding to the parallel tetramolecular qDNA Q4. The results of binding experiments performed using CD spectroscopy suggested that (12) exhibits a significant level of affinity towards most types of DNA, while (4) shows a preference for interacting with parallel, unimolecular qDNA molecules. Complex (4) produced the lowest values of DC50 in FID assays performed using parallel Q1 or Q4, confirming its affinity for these qDNA molecules. The results of FRET melting experiments provided further evidence that (12), along with (8), can interact extensively with anti-parallel unimolecular qDNA. Experiments which monitored the effect of the nickel complexes on the melting temperature of D2 showed that none had a stabilising effect on this dsDNA molecule.
一系列新型的镍席夫碱配合物，以及具有不对称结构的相关配体的镍配合物，已经通过微量分析、1H 和 13C NMR 光谱和 ESI-MS 进行了制备和表征。席夫碱配体是通过涉及乙二胺和不同的二苯甲酮衍生物的缩合反应制备的。还确定了八个配合物的固态结构，结果表明每个配合物在金属离子周围都具有规则的正方形平面配位几何形状。许多新的配合物至少具有一个，在许多情况下具有两个，可质子化的悬垂基团，这增强了它们在水中的溶解度。这使得可以使用各种仪器方法来探索这些配合物的 DNA 结合特性，包括 ESI-MS、圆二色性 (CD) 光谱、FRET 熔融测定法和 FID 测定法以及分子对接研究。使用 ESI-MS 进行的实验结果表明，没有一个镍配合物对双链 DNA（dsDNA）分子 D2 或平行单分子四链体 DNA（qDNA）分子 Q1 表现出高亲和力。相比之下，配合物（8）和（12）都给出了反映与平行四联体 qDNA Q4 具有显著结合水平的光谱。使用 CD 光谱进行的结合实验结果表明，（12）对大多数类型的 DNA 表现出显著的亲和力，而（4）则表现出与平行单分子 qDNA 分子相互作用的偏好。在使用平行 Q1 或 Q4 进行的 FID 测定中，（4）产生的 DC50 值最低，证实了其对这些 qDNA 分子的亲和力。FRET 熔融实验的结果提供了进一步的证据，表明（12）与（8）一起，可以与反平行单分子 qDNA 广泛相互作用。监测镍配合物对 D2 熔点影响的实验表明，它们对该 dsDNA 分子均无稳定作用。
