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带有芳烃配体的 Pd(II)/1,10-菲咯啉复合物:关于 N- 与 O-配位在调节细胞活性以及对 DNA 和 RNA 的结合能力方面的作用。

Pd(II)/1,10-phenanthroline complexes bearing arene ligands: On the role of N- vs O-coordination to tune their cellular activity and binding ability towards DNA and RNA.

发表日期:2024 Sep 28
作者: Francesca Binacchi, Damiano Cirri, Eleonora Bimbi, Natalia Busto, Alessandro Pratesi, Tarita Biver
来源: JOURNAL OF INORGANIC BIOCHEMISTRY

摘要:

已经合成了三种基于 Pd(II) 的 1,10-菲咯啉和 N-或 O-配位配体的复合物,并用不同的相关生物底物(如双链 DNA、RNA 双螺旋和三螺旋、不同的 DNA G-四链体)进行了测试。构象和牛血清白蛋白。这里出现了 N-配位元件与 O-配位元件和结合机制之间的相关性,其中 N-配位配体被证明是最有前途的。这些结果也在细胞实验中得到了证实。 Pd(II) 与萘-1,8-二胺的络合物是一种能够被 BSA 携带的络合物,能够强烈结合核酸,产生活性氧 (ROS),并显示出最佳的细胞性能(毒性低)对健康细胞和对顺铂耐药的癌细胞系具有高毒性)。相反,与 1,2-苯二醇形成的复合物可能被 BSA 隔离,与核酸的结合较弱,不产生 ROS,细胞活性较差。与苯-1,2-二胺的络合物位于中间。讨论了其他机制细节,表明生物物理行为是芳香性、电荷以及 N 或 O 配位贡献的总和。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。
Three Pd(II)-based complexes of 1,10-phenanthroline and N- or O-coordinating ligands have been synthesised and tested with different relevant biosubstrates like double-stranded DNA, double and triple helix of RNA, DNA G-quadruplexes of different conformations and bovine serum albumin. Here a correlation between N- vs O-coordinating elements and binding mechanism emerged, where the N-coordinating ligands proved to be the most promising. These outcomes were confirmed also in the cellular experiments. The Pd(II) complex with naphthalene-1,8-diamine is the one that is able to be carried by BSA, to strongly bind nucleic acids, to produce reactive oxygen species (ROS) and to show the best cellular performances (poorly toxic towards healthy cells and highly toxic against the cisplatin-resistant cancer cell line). On the opposite, the complex with benzene-1,2-diolate may be sequestered by BSA, weakly binds nucleic acids, does not produce ROS and shows poor cellular activity. The complex with benzene-1,2-diamine stays in between. Other mechanistic details are discussed which show that the biophysical behaviour is the sum of the contribution of aromaticity, charge and N- or O-coordination.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.