Computational and Theoretical Chemistry ( IF 2.8 ) Pub Date : 2019-12-03 , DOI: 10.1016/j.comptc.2019.112664 Amit Kumar Pradhan , Paritosh Mondal
Keppler type water-soluble ((ImH)[trans-RuCl4(Im)2], Im = imidazole), ICR (or KP418) exhibits promising anticancer activity against colorectal cancer. Interaction of aquated ICR complexes; i.e., [trans-RuCl3(H2O)(Im)2] (monoaqua ICR) and [trans-RuCl2(H2O)2(Im)2]+ (diaqua ICR) with cysteine (Cys), guanine (G), and adenine (A) residues have been investigated in details by DFT method and CPCM solvation model. Activation free energy for the substitution of aqua ligand from diaquated ICR by Cys is found to be apparently lower (13.28 kcal/mol) in aqueous phase and corresponding rate constant value is calculated to be = 1.52×103 s-1. Calculated activation free energy values suggest that substitution of aqua ligand from diaqua ICR is observed to be more favourable by Cys, G or A in comparison to monoaqua ICR. Surprisingly, intermolecular hydrogen bondings play a significant role in stabilizing entire geometry. Furthermore, calculated net atomic charges based on natural population analysis show charge redistribution on interaction with Cys, G and A.
中文翻译:
半胱氨酸和DNA嘌呤碱基与水合钌(III)抗癌药(ImH)[反式RuCl 4(Im)2 ]相互作用的量子化学研究
开普勒型水溶性((ImH)[反式RuCl 4(Im)2 ],Im =咪唑),ICR(或KP418)对大肠癌表现出有希望的抗癌活性。水合ICR配合物的相互作用;即,[trans-RuCl 3(H 2 O)(Im)2 ](一元ICR)和[trans-RuCl 2(H 2 O)2(Im)2 ] +(diaqua ICR)与半胱氨酸(Cys),鸟嘌呤(G)和腺嘌呤(A)残留物已通过DFT方法和CPCM溶剂化模型进行了详细研究。发现用Cys取代过饱和ICR取代过饱和ICR中的水配体的活化自由能明显较低(13.28 kcal / mol),并且计算出相应的速率常数= 1.52×10 3 s -1。计算得到的活化自由能值表明,与单水ICR相比,用Cys,G或A观察到来自diaqua ICR的水配体取代更有利。出乎意料的是,分子间氢键在稳定整个几何结构中起着重要作用。此外,基于自然种群分析计算出的净原子电荷显示出与Cys,G和A相互作用时电荷的重新分布。