Department of Chemistry, University of Isfahan, Isfahan, 81746-73441, Iran.
J Biol Inorg Chem. 2018 Mar;23(2):181-192. doi: 10.1007/s00775-017-1505-9. Epub 2017 Nov 8.
The interaction of three complexes [Zn(II), Cu(II), and V(IV)] derived from an asymmetric bidentate Schiff-base ligand with DNA and HSA was studied using fluorescence quenching, UV-Vis spectroscopy, viscosity measurements, and computational methods [molecular docking and our Own N-layered Integrated molecular Orbital and molecular Mechanics (ONIOM)]. The obtained results revealed that the DNA and HSA affinities for binding of the synthesized compounds follow as V(IV) > Zn(II) > Cu(II) and Zn(II) > V(IV) > Cu(II), respectively. The distance between these compounds and HSA was obtained based on the Förster's theory of non-radiative energy transfer. Furthermore, computational molecular docking was carried out to investigate the DNA- and HSA-binding pose of the compounds. Molecular docking calculations showed that H-bond, hydrophobic, and π-cation interactions have dominant role in stability of the compound-HSA complexes. ONIOM method was utilized to investigate the HSA binding of the compounds more precisely in which molecular-mechanics method (UFF) and semi-empirical method (PM6) were selected for the low layer and the high layer, respectively. The results show that the structural parameters of the compounds changed along with binding, indicating the strong interaction between the compounds with HSA and DNA. Viscosity measurements as well as computational docking data suggest that all metal complexes interact with DNA, presumably by groove-binding mechanism.
用荧光猝灭、紫外-可见光谱、粘度测量和计算方法[分子对接和我们自己的 N 层综合分子轨道和分子力学（ONIOM）]研究了三种配合物[Zn(II)、Cu(II)和 V(IV)]与 DNA 和 HSA 的相互作用，这些配合物是由不对称双齿席夫碱配体衍生而来的。实验结果表明，所合成化合物与 DNA 和 HSA 的结合亲和力顺序为 V(IV) > Zn(II) > Cu(II)和 Zn(II) > V(IV) > Cu(II)。根据福斯特非辐射能量转移理论，获得了这些化合物与 HSA 之间的距离。此外，还进行了计算分子对接，以研究化合物与 DNA 和 HSA 的结合构象。分子对接计算表明，氢键、疏水和π-阳离子相互作用对化合物-HSA 配合物的稳定性起主导作用。ONIOM 方法用于更精确地研究化合物与 HSA 的结合，其中选择分子力学方法（UFF）和半经验方法（PM6）分别用于低层和高层。结果表明，随着结合的进行，化合物的结构参数发生变化，表明化合物与 HSA 和 DNA 之间存在强烈的相互作用。粘度测量和计算对接数据表明，所有金属配合物都与 DNA 相互作用，可能通过沟结合机制。
