采用密度泛函理论（DFT）计算和分子对接方法对顺铂类似物 Pt(II)/Pd(II) 配合物的水解机制进行理论研究，探讨其与 DNA 和 HSA 的相互作用。
Theoretical investigation on hydrolysis mechanism of cis-platin analogous Pt(II)/Pd(II) complex by DFT calculation and molecular docking approach for their interaction with DNA & HSA.
机构信息
Department of Chemistry, National Institute of Technology Durgapur, M. G. Avenue, Durgapur, 713209, West Bengal, India.
Department of Biotechnology, National Institute of Technology Durgapur, M. G. Avenue, Durgapur, 713209, West Bengal, India.
出版信息
J Mol Graph Model. 2022 Dec;117:108314. doi: 10.1016/j.jmgm.2022.108314. Epub 2022 Aug 23.
The properties to be an active drug candidate of the complex Pt(TEEDA)Cl, C1; Pd(TEEDA)Cl, C2 and their hydrolysed product [Pt(TEEDA)(OH)], C1' and [Pd(TEEDA)(OH)], C2' were predicted by Lipinski's rule of 5 and PASS (prediction of activity spectra for substances) web tool. Their structural profile, HOMO-LUMO energy and electronic potential surface ware analysed by DFT calculation. Their TD-DFT spectra were compared with experimental UV-Vis spectra. The hydrolysis mechanisms of C1 & C2 to the diaqua form C1' and C2' were extensively investigated by DFT method in different levels of theory and using CPCM/water model and compared with recognised Pt based anticancer drugs. All the stationary states, including the transition state for the reactions were identified by the DFT calculation. The IRC calculation confirmed that the transition states are well connected and corelate with reactants and products. Interaction of the complexes with DNA & HSA was also investigated by molecular docking study.
该配合物 Pt(TEEDA)Cl，C1；Pd(TEEDA)Cl，C2 及其水解产物[Pt(TEEDA)(OH)]，C1'和[Pd(TEEDA)(OH)]，C2'被 Lipinski 规则 5 和 PASS（物质活性光谱预测）网络工具预测为具有成为活性药物候选物的特性。通过 DFT 计算分析了它们的结构特征、HOMO-LUMO 能量和电子势能面。将它们的 TD-DFT 光谱与实验的 UV-Vis 光谱进行了比较。通过 DFT 方法在不同理论水平和使用 CPCM/水模型对 C1 和 C2 到二水合形式 C1'和 C2'的水解机制进行了广泛的研究，并与公认的基于铂的抗癌药物进行了比较。通过 DFT 计算确定了所有的稳定态，包括反应的过渡态。IRC 计算证实了过渡态与反应物和产物之间的连接良好且相关。还通过分子对接研究研究了配合物与 DNA 和 HSA 的相互作用。
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