Nikolaev Institute of Inorganic Chemistry, Siberian Branch of the Russian Academy of Sciences (SB RAS), 3 Acad. Lavrentiev Avenue, Novosibirsk 630090, Russia.
Novosibirsk State University, 1 Pirogov Street, Novosibirsk 630090, Russia.
Inorg Chem. 2023 Jul 24;62(29):11541-11553. doi: 10.1021/acs.inorgchem.3c01172. Epub 2023 Jul 7.
A series of heteroleptic bipyridine Pd(II) complexes based on 1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene (dpp-Bian) or 1,2-bis[(2,4,6-trimethylphenyl)imino]acenaphthene (tmp-Bian) were prepared. All complexes were fully characterized by spectrochemical methods, and their crystal structures were confirmed by X-ray diffraction analysis. The 72 h stability of heteroleptic bipyridine Pd(II) complexes with Bian ligands under physiological conditions was investigated using H NMR spectroscopy. The anticancer activity of all complexes was assessed in a panel of cancer cell lines in comparison with uncoordinated ligands and clinically used drugs cisplatin and doxorubicin. The ability of the complexes to bind DNA was investigated using several methods, including EtBr replacement assay, density functional theory calculations, circular dichroism spectroscopy, DNA gel electrophoresis, and TUNEL assay. The electrochemical activity of all complexes and the uncoordinated ligands was studied using cyclic voltammetry, and reactive oxygen species production in cancer cells was investigated using confocal microscopy. Heteroleptic bipyridine Pd-Bian complexes were cytotoxic in a low micromolar concentration range and showed some selectivity toward cancer cells in comparison with noncancerous MRC-5 lung fibroblasts.
一系列基于 1,2-双[(2,6-二异丙基苯基)亚氨基]吖啶（dpp-Bian）或 1,2-双[(2,4,6-三甲苯基)亚氨基]吖啶（tmp-Bian）的异双核联吡啶 Pd(II)配合物被制备。所有配合物均通过光谱化学方法进行了充分表征，并通过 X 射线衍射分析确认了其晶体结构。使用 H NMR 光谱法研究了在生理条件下 Bian 配体的异双核联吡啶 Pd(II)配合物的 72 h 稳定性。通过与未配位的配体以及临床使用的顺铂和阿霉素进行比较，评估了所有配合物在一系列癌细胞系中的抗癌活性。使用几种方法研究了配合物与 DNA 的结合能力，包括 EtBr 取代实验、密度泛函理论计算、圆二色光谱、DNA 凝胶电泳和 TUNEL 实验。使用循环伏安法研究了所有配合物和未配位配体的电化学活性，并使用共聚焦显微镜研究了癌细胞中活性氧物质的产生。异双核联吡啶 Pd-Bian 配合物在低微摩尔浓度范围内具有细胞毒性，并显示出与非癌细胞 MRC-5 肺成纤维细胞相比对癌细胞的一些选择性。
