School of Chemistry, University of Wollongong, NSW 2522, Australia.
Dalton Trans. 2018 Oct 2;47(38):13573-13591. doi: 10.1039/c8dt02727g.
Two different series of nickel Schiff base complexes were prepared as part of a study aimed at discovering new compounds with high affinity and selectivity for quadruplex DNA (qDNA). The new complexes were prepared by modification of a literature method for synthesising N,N'-bis-(4-((1-(2-ethyl)piperidine)-oxy)salicylidene)phenylenediaminenickel(ii) (complex (1)). For Series 1 complexes, the phenylenediamine head group of the literature complex was replaced with ethylenediamine, phenanthrenediamine, R,R- and S,S-diaminocyclohexane. These complexes, as well as an asymmetric molecule featuring a naphthalene moiety on one side and a single ethyl piperidinyl salicylidene group on the other, were prepared in order to examine the effect of varying the number and position of aromatic groups on DNA binding. Series 2 complexes were isomers of those in Series 1, in which pendant ethyl piperidine groups were located at different positions. All new complexes were characterised by 1D and 2D NMR spectroscopic methods alongside microanalysis and ESI-MS. In addition, the solid state structures of eight new complexes were determined using single crystal X-ray diffraction methods. N,N'-Bis-(4-((1-(2-ethyl)piperidine)oxy)-salicylidine)diaminophenanthrenenickel(ii) (9), was shown by ESI-MS, CD spectroscopy and UV melting studies to exhibit a greater affinity towards, and ability to stabilise, dsDNA than all other complexes in the first series. ESI-MS revealed (9) to have a strong tendency to form a 1 : 1 complex with the tetramolecular, parallel qDNA molecule Q4, however it exhibited low affinity towards the parallel unimolecular qDNA molecule Q1. The enantiomeric complexes (5) and (7), featuring R,R- and S,S-diaminocyclohexane moieties, respectively, showed similar binding profiles towards all DNA molecules investigated, whereas the asymmetric complex (11), exhibited very low DNA affinity in all cases. Series 2 complexes showed very similar DNA affinity and selectivity to their isomeric counterparts in Series 1. For example, (14) and (15), both of which contain a phenylenediamine head group, showed higher affinity towards D2, Q1 and Q4, than any of the other Series 2 complexes. In addition, complex (21), which contains a meso-1,2-diphenylethylenediamine moiety, interacted strongly with Q4, but not D2 or Q1. This observation was very similar to that made previously for the isomeric complex (3).
作为发现与四链体 DNA（qDNA）具有高亲和力和选择性的新化合物的研究的一部分，合成了两个不同系列的镍希夫碱配合物。新配合物是通过修改文献中合成 N,N'-双-(4-((1-(2-乙基)哌啶)-氧基)水杨醛基)苯二胺镍(ii)（配合物（1）的方法制备的。对于第 1 系列配合物，文献配合物的苯二胺头基被乙二胺、菲咯啉二胺、R,R-和 S,S-二氨基环己烷取代。为了研究改变芳族基团的数量和位置对 DNA 结合的影响，制备了这些配合物以及一侧带有萘部分而另一侧带有单个乙基哌啶基水杨醛基的不对称分子。第 2 系列配合物是第 1 系列配合物的异构体，其中侧链乙基哌啶基团位于不同位置。所有新配合物均通过 1D 和 2D NMR 光谱法以及微量分析和 ESI-MS 进行了表征。此外，还使用单晶 X 射线衍射法确定了八个新配合物的固体结构。通过 ESI-MS、CD 光谱和 UV 熔融研究表明，N,N'-双-(4-((1-(2-乙基)哌啶)氧基)水杨醛基)二氨基菲咯啉镍(ii)（9）与第一个系列中的所有其他配合物相比，对 dsDNA 的亲和力更高，并且能够更稳定地稳定 dsDNA。ESI-MS 显示（9）与四分子平行 qDNA 分子 Q4 形成 1:1 配合物的趋势很强，但是它与平行单分子 qDNA 分子 Q1 的亲和力较低。具有 R,R-和 S,S-二氨基环己烷部分的对映体配合物（5）和（7）对所有研究的 DNA 分子表现出相似的结合谱，而不对称配合物（11）在所有情况下都表现出非常低的 DNA 亲和力。第 2 系列配合物与第 1 系列的异构体具有非常相似的 DNA 亲和力和选择性。例如，（14）和（15）均包含苯二胺头基，它们对 D2、Q1 和 Q4 的亲和力高于第 2 系列中的任何其他配合物。此外，含有间-1,2-二苯乙基二胺部分的配合物（21）与 Q4 强烈相互作用，但与 D2 或 Q1 不相互作用。这一观察结果与之前对异构体（3）的观察结果非常相似。
