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Abstract：
A series of mono- and heteronuclear platinum(II) and zinc(II) complexes with 4,4\',4″-tri-tert-butyl-2,2\':6\',2″-terpyridine ligand were synthesized and characterized. The DNA and protein binding properties of [ZnCl2(terpytBu)] (C1), [{cis-PtCl(NH3)2(μ-pyrazine)ZnCl(terpytBu)}](ClO4)2 (C2), [{trans-PtCl(NH3)2(μ-pyrazine)ZnCl(terpytBu)}](ClO4)2 (C3), [{cis-PtCl(NH3)2(μ-4,4\'-bipyridyl)ZnCl(terpytBu)}](CIO4)2 (C4) and [{trans-PtCl(NH3)2(μ-4,4\'-bipyridyl)ZnCl(terpytBu)}](CIO4)2 (C5) (where terpytBu = 4,4\',4″-tri-tert-butyl-2,2\':6\',2″-terpyridine), were investigated by electronic absorption, fluorescence spectroscopic, and molecular docking methods. Complexes featuring transplatin exhibited lower Kb and Ksv constant values compared to cisplatin analogs. The lowest Ksv value belonged to complex C1, while C4 exhibited the highest. Molecular docking studies reveal that the binding of complex C1 to DNA is due to van der Waals forces, while that of C2-C5 is due to conventional hydrogen bonds and van der Waals forces. The tested complexes exhibited variable cytotoxicity toward mouse colorectal carcinoma (CT26), human colorectal carcinoma (HCT116 and SW480), and non-cancerous mouse mesenchymal stem cells (mMSC). Particularly, the mononuclear C1 complex showed pronounced selectivity toward cancer cells over non-cancerous mMSC. The C1 complex notably induced apoptosis in CT26 cells, effectively arrested the cell cycle in the G0/G1 phase, and selectively down-regulated Cyclin D.
摘要：
一系列单核和异核铂（II）和锌（II）配合物，具有4,4'，4″-三叔丁基-2,2\':6\',合成并表征了2″-三联吡啶配体。[ZnCl2（terpytBu）]（C1）的DNA和蛋白质结合特性，[{cis-PtCl(NH3)2(μ-吡嗪)ZnCl(terpytBu)}](ClO4)2(C2),[{反式-PtCl(NH3)2(μ-吡嗪)ZnCl(terpytBu)}](ClO4)2(C3),[{顺式-PtCl(NH3)2(μ-4,4'-联吡啶)ZnCl(terpytBu)}](ClO4)2(C4)和[{反式-PtCl(NH3)2(μ-4,4'-联吡啶)ZnCl(terpytBu)}](ClO4)2(C5)(其中terpytBu=4,4″-三叔丁基-2,2\':6\',2″-三吡啶)，通过电子吸收进行研究，荧光光谱,和分子对接方法。与顺铂类似物相比,以转铂为特征的复合物表现出较低的Kb和Ksv常数值。Ksv值最低属于复合体C1,C4最高。分子对接研究表明，复合物C1与DNA的结合是由于范德华力，而C2-C5是由于常规的氢键和范德华力。测试的复合物对小鼠结直肠癌（CT26）表现出可变的细胞毒性，人类大肠癌（HCT116和SW480），和非癌小鼠间充质干细胞(mMSC)。特别是,与非癌性mMSC相比，单核C1复合物对癌细胞显示出明显的选择性。C1复合物显著诱导CT26细胞凋亡,有效地将细胞周期阻滞在G0/G1期，选择性下调细胞周期蛋白D
