Department of Chemistry, Cotton University, Guwahati-781001, Assam, India.
Departament de Química, Universitat de les Illes Balears, Crta de Valldemossa km 7.7, 07122 Palma de Mallorca, Baleares, Spain.
Dalton Trans. 2020 Jul 21;49(28):9863-9881. doi: 10.1039/d0dt01007c.
Two new coordination compounds involving hexanuclear Cu(ii), viz., Cu6(phen)6(μ4-adpt)4(H2O)24·10H2O (1) and polymeric Co(ii), viz., {[(μ2-adpt)4Co(μ2-H2O)2Co(H2O)4]·4H2O}n (2) (phen = 1,10-phenanthroline; adpt = adipate) have been synthesized and characterized using elemental analysis, TGA, spectroscopic (IR, electronic and ESR), PXRD and single crystal X-ray diffraction techniques. Discrete nitrate-water clusters involving the [(H2O)3NO3]- core in 1 and linear (H2O)4 core in 2 provide stability to the layered network of the structures of the compounds. Interestingly, the water clusters in polymer 2 are encapsulated as guests in the voids of the host square grid that extends in 2D architecture. Theoretical studies have revealed the presence of interesting energetically significant cooperativity effects of π-stacking contacts that are responsible for the hexanuclear structure of compound 1. Both complexes significantly inhibit cell viability by inducing apoptotic cell death in the DL cancer cell line with negligible cytotoxicity in normal cells (PBMC). An assessment of ROS (reactive oxygen species) level study revealed a rapid increase of ROS in DL cells indicating cytotoxicity of the compounds against the DL cells. A decrease in MMP (mitochondrial membrane potential) is associated with an opening of the mitochondrial permeability transition pores which corroborates the apoptotic features of 1 and 2. The mode of action of the cytotoxic activities of the compounds has been explored with respect to their in silico docking ability and further inhibition of antiapoptotic proteins as evidenced by western blot analysis. SAR analyses based on pharmacophore modelling reveal that the molecular features of the structures of the compounds play important roles in biological activities.
两种新的涉及六核铜（ii）的配位化合物，即[Cu6（phen）6（μ4-adpt）4（H2O）2]（NO3）4·10H2O（1）和聚合钴（ii），即{[(μ2-adpt)4Co（μ2-H2O）2Co（H2O）4]·4H2O}n（2）（phen = 1,10-菲咯啉；adpt = 己二酸）已通过元素分析、TGA、光谱（IR、电子和 ESR）、PXRD 和单晶 X 射线衍射技术进行了合成和表征。在 1 中，涉及[(H2O)3NO3]-核心的离散硝酸盐-水簇和在 2 中线性(H2O)4核心提供了化合物结构的层状网络的稳定性。有趣的是，聚合物 2 中的水簇被封装为主体正方形网格空隙中的客体，该网格在二维结构中延伸。理论研究表明，π-堆积接触存在有趣的能量显著协同作用，这是化合物 1 具有六核结构的原因。两种复合物都通过诱导凋亡性细胞死亡显著抑制 DL 癌细胞系的细胞活力，而在正常细胞（PBMC）中几乎没有细胞毒性。活性氧（ROS）水平研究的评估表明，DL 细胞中 ROS 迅速增加，表明化合物对 DL 细胞具有细胞毒性。MMP（线粒体膜电位）的降低与线粒体通透性转换孔的打开有关，这与 1 和 2 的凋亡特征相符。通过 Western blot 分析进一步证实了化合物的细胞毒性作用的作用机制是与它们的计算机对接能力和对抗凋亡蛋白的进一步抑制有关。基于药效团模型的 SAR 分析表明，化合物结构的分子特征在生物活性中起着重要作用。
