Costa Joana P, Justino Gonçalo C, Marques Fernanda, Carvalho M Fernanda N N
Centro de Química Estrutural, Institute of Molecular Sciences, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal.
Escola Superior de Tecnologia do Barreiro, Instituto Politécnico de Setúbal, R. Américo da Silva Marinho, 2839-001 Lavradio, Portugal.
Molecules. 2025 Jun 30;30(13):2817. doi: 10.3390/molecules30132817.
Cyclic voltammetry (CV) is an accessible, readily available, non-expensive technique that can be used to search for the interaction of compounds with DNA and detect the strongest DNA-binding from a set of compounds, therefore allowing for the optimization of the number of cytotoxicity assays. Focusing on this electrochemical approach, the study of twenty-seven camphorimine silver complexes of six different families was performed aiming at detecting interactions with calf thymus DNA (CT-DNA). All of the complexes display at least two cathodic waves attributed respectively to the Ag(I)→Ag(0) (higher potential) and ligand based (lower potential) reductions. In the presence of CT-DNA, a negative shift in the potential of the Ag(I)→Ag(0) reduction was observed in all cases. Additional changes in the potential of the waves, attributed to the ligand-based reduction, were also observed. The formation of a light grey product adherent to the Pt electrode in the case of {Ag(OH)} and {Ag(µ-O)} complexes further corroborates the interaction of the complexes with CT-DNA detected by CV. The morphologic analysis of the light grey material was made by scanning electronic microscopy (SEM). The magnitude of the shift in the potential of the Ag(I)→Ag(0) reduction in the presence of CT-DNA differs among the families of the complexes. The complexes based on {Ag(NO)} exhibit higher potential shifts than those based on {Ag(OH)}, while the characteristics of the ligand (L-Y, L-Y, L-Z) and the imine substituents (Y,Z) fine-tune the potential shifts. The energy values calculated by docking corroborate the tendency in the magnitude of the interaction between the complexes and CT-DNA established by the reaction coefficient ratios (Q/Q). The molecular docking study extended the information regarding the type of interaction beyond the usual intercalation, groove binding, or electrostatic modes that are typically reported, allowing a finer understanding of the non-covalent interactions involved. The rationalization of the CV and cytotoxicity data for the Ag(I) camphorimine complexes support a direct relationship between the shifts in the potential and the cytotoxic activities of the complexes, aiding the decision on whether the cytotoxicity of a complex from a family is worthy of evaluation.
循环伏安法（CV）是一种易于使用、成本低廉的技术，可用于研究化合物与DNA的相互作用，并从一组化合物中检测出最强的DNA结合能力，从而有助于优化细胞毒性测定的数量。基于这种电化学方法，对六个不同家族的27种樟脑亚胺银配合物进行了研究，旨在检测它们与小牛胸腺DNA（CT-DNA）的相互作用。所有配合物均显示至少两个阴极波，分别归因于Ag(I)→Ag(0)（较高电位）和基于配体的（较低电位）还原。在CT-DNA存在的情况下，所有情况下均观察到Ag(I)→Ag(0)还原电位的负移。还观察到归因于基于配体还原的波电位的其他变化。对于{Ag(OH)}和{Ag(µ-O)}配合物，在Pt电极上形成浅灰色产物，进一步证实了通过循环伏安法检测到的配合物与CT-DNA的相互作用。通过扫描电子显微镜（SEM）对浅灰色物质进行了形态分析。在CT-DNA存在下，Ag(I)→Ag(0)还原电位的偏移幅度在不同家族的配合物之间有所不同。基于{Ag(NO)}的配合物比基于{Ag(OH)}的配合物表现出更高的电位偏移，而配体（L-Y、L-Y、L-Z）和亚胺取代基（Y、Z）的特性微调了电位偏移。通过对接计算得到的能量值证实了由反应系数比（Q/Q）确定的配合物与CT-DNA之间相互作用强度的趋势。分子对接研究扩展了有关相互作用类型的信息，超出了通常报道的嵌入、沟槽结合或静电模式，从而能够更深入地理解所涉及的非共价相互作用。Ag(I)樟脑亚胺配合物的循环伏安法和细胞毒性数据的合理化支持了电位偏移与配合物细胞毒性活性之间的直接关系，有助于决定一个家族中配合物的细胞毒性是否值得评估。
