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首页> 外文期刊>Structural Chemistry >Effect of axial ligands on the mechanisms of action of Ru(III) complexes structurally similar to NAMI-A: a DFT study
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Effect of axial ligands on the mechanisms of action of Ru(III) complexes structurally similar to NAMI-A: a DFT study

机译：轴配体对鲁（III）复合物的作用机制的影响与Nami-A相似：DFT研究

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Although the mechanisms of action of Ru(III) anticancer drugs including NAMI-A and KP1019 are not properly understood, it is reported that they are readily aquated in vivo before reacting to the biological targets and their cytotoxic activities are mainly attributed to their binding with DNA. In the present contribution in order to understand how changing the axial ligands affects the mechanisms of action of Ru(III)-based drugs which are structurally similar to NAMI-A, we study here the aquation reactions (substitution of one chloride anion (Cl-) ligand by a water molecule) of six structurally similar Ru(III) complexes (1-6) including NAMI-A (complex 1) and KP1019 (complex 2) as well as the reactions of their mono-aquated products with the N3, N7 and O6 sites of guanine at the M06-2X/(LanL2DZ+6-311+G**)//M06-2X/(LanL2DZ+6-31G**) level of density functional theory in gas phase and aqueous media. It is found that the aquation reaction of every Ru(III) complex occurs through a single transition state where a chloride ligand of the complex is replaced by a H2O molecule. The activation free energies (Delta G(b)) and rate constants of aquation reactions show that the complex 6 would get aquated in biological media more readily than other complexes. The rate constant of aquation of complex 6 is 7.98 x 10(-3) s(-1). It is evident from our calculations that axial ligands play important role in the aquation of Ru(III) complexes structurally similar to NAMI-A, but they do not obey any specific trends. Both the calculated reaction enthalpies (Delta H-f) and reaction free energies (Delta G(f)) show that reactions of Ru(III) complexes (1-6) at the N3, N7 and O6 sites of guanine are exothermic and would occur spontaneously. It is found that KP1019 would react more favourably than NAMI-A at the N3, N7 and O6 of guanine, in agreement with experimental observations. Further, among all the complexes studied here, reactions of complex 6 at the different sites of guanine are most exothermic in aqueous media.
机译：虽然ru（III）抗癌药物的作用机制尚未正确理解，但据报道，在对生物靶标反应之前，它们在体内易患它们，并且它们的细胞毒性活动主要归因于它们的结合脱氧核糖核酸。在目前的贡献中，为了了解轴向配体的改变程度如何影响ru（III）的作用机制，这些药物在结构上类似于Nami-A的药物，我们在此研究水中反应（取代一只氯化物阴离子（CL-） ）通过水分子的配体）六种结构上类似的ru（iii）配合物（1-6），包括Nami-a（络合物1）和KP1019（复合物2）以及它们的单含水产品与N3的反应，鸟嘌呤的N7和O6位点在M06-2X /（LANL2DZ + 6-311 + G **）// M06-2X /（LANL2DZ + 6-31G **）气相和水性介质中的密度泛函理论水平。发现每种Ru（III）复合物的水中反应通过单个过渡状态发生，其中复合物的氯化物配体被H2O分子取代。活化的自由能量（Delta g（b））和水生反应的速率常数表明，复合体6将比其他复合物更容易地进入生物介质。复合物6的水中速率常数为7.98 x 10（-3）s（-1）。从我们的计算中显而易见的是，轴向配体在ru（iii）复合物的水中起着重要作用，这些复合物与Nami-a类似地相似，但它们并没有遵守任何特定趋势。计算的反应焓（Delta HF）和反应无δ）表明u3，N7和鸟嘌呤的N 3，N7和O6位点的Ru（III）复合物（1-6）的反应是放热的，并且会自发发生。发现KP1019与鸟嘌呤的N3，N7和O6的NAMI-A更有利，同时与实验观察结果更良好。此外，在这里研究的所有复合物中，在鸟嘌呤不同部位的复合物6的反应在水性介质中最放热。

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