Several studies with substitution-inert polynuclear platinum(II) complexes (SI-PPC) have been carried out in recent years due to the form of DNA binding presented by these compounds. This form of bonding is achieved by molecular recognition through the formation of non-covalent structures, commonly called phosphate clamps and forks, which generate small extensions of the major and minor grooves. In this work, we use molecular dynamics simulations (MD) to study the formation of these cyclical structures between six different SI-PPCs and a double DNA dodecamer, here called 24_bp_DNA. The results showed the influence of the complex expressed on the number of phosphate clamps and forks formed. Based on the conformational characterization of the DNA fragment, we show that the studied SI-PPCs interact preferentially in the minor groove, causing groove spanning, except for two of them, Monoplatin and AH44. The phosphates of C–G pairs are the main sites for such non-covalent interactions. The Gibbs interaction energy of solvated species points out to AH78P, AH78H, and TriplatinNC as the most probable ones when coupled with DNA. As far as we know, this work is the very first one related to SI-PPCs which brings MD simulations and a complete analysis of the non-covalent interactions with a double DNA dodecamer.

近年来，由于这些化合物呈现的DNA结合形式，对取代惰性多核铂（II）配合物（SI-PPC）进行了数项研究。这种结合形式是通过形成非共价结构（通常称为磷酸盐钳和叉）的分子识别来实现的，该非共价结构会在主凹槽和副凹槽中产生小的延伸。在这项工作中，我们使用分子动力学模拟（MD）研究了六个不同的SI-PPC和双DNA十二聚体（此处称为24_bp_DNA）之间这些循环结构的形成。结果表明复合物表达对形成的磷酸盐钳和叉的数量的影响。根据DNA片段的构象特征，我们表明，所研究的SI-PPC在小沟中优先相互作用，除了其中两个，Monoplatin和AH44以外，会引起沟槽扩展。C–G对的磷酸酯是此类非共价相互作用的主要部位。当与DNA结合时，溶剂化物种的吉布斯相互作用能指出AH78P，AH78H和TriplatinNC是最可能的相互作用能。据我们所知，这项工作是与SI-PPC相关的第一项工作，它带来了MD模拟以及对双DNA dodecamer的非共价相互作用的完整分析。