物理化学学报 >> 2009, Vol. 25 >> Issue (12): 2551-2557.doi: 10.3866/PKU.WHXB20091203

研究论文 上一篇    下一篇

含平面胺配体的反式二价钯配合物与DNA碱基的作用

张东东, 周立新   

  1. 暨南大学化学系, 广州 510632
  • 收稿日期:2009-07-30 修回日期:2009-08-31 发布日期:2009-11-27
  • 通讯作者: 周立新 E-mail:tlzhou@jnu.edu.cn

Interaction of a trans-Palladium(II) Complex Containing Planar Amine Ligands with DNA Bases

ZHANG Dong-Dong, ZHOU Li-Xin   

  1. Department of Chemistry, Jinan University, Guangzhou 510632, P. R. China
  • Received:2009-07-30 Revised:2009-08-31 Published:2009-11-27
  • Contact: ZHOU Li-Xin E-mail:tlzhou@jnu.edu.cn

摘要:

含大的平面胺配体的二价钯金属配合物在当前的抗肿瘤药物设计中代表着一类具有重要发展前途的先导结构. 由于大的平面胺配体具有较大的空间位阻, 目前主要的问题是这类化合物能否和DNA碱基结合形成单功能和双功能加合物. 我们采用密度泛函理论和等电聚焦连续极化(IEF-PCM)溶剂化模型研究了trans-PdCl2L2(L:2-羟基吡啶)的钯配合物与DNA碱基的作用. 该化合物与DNA形成单功能和双功能加合物反应的活化自由能均低于铂类抗肿瘤药. 所有反应在水溶液中均为放热反应. 结果表明, 这一大的平面胺配体不会阻碍该化合物与DNA碱基形成双功能加合物, 而且该化合物与DNA的单功能和双功能结合的速率会大于铂类化合物.

关键词: 密度泛函理论, 嘌呤碱基, 胞嘧啶, 抗癌, 过渡态

Abstract:

Palladium(II) complexes coordinated to large planar amine ligands represent a lead structure of considerable interest in current antitumor drug design. However, the question is whether these complexes can bind to DNA bases affording bifunctional adducts for great steric hindrance provided by the bulky ligands. We studied the interaction of the palladium(II) complex, PdCl2L2, where L was 2-hydroxypydridine, with DNA bases using density functional theory and combining with isoelectric focusing polarized continuum (IEF-PCM) solvation model. Activation free energies for the complex monofunctional and bifunctional binding to DNA bases were lower than those for platinum-based antitumor agents. All reactions under study were exothermic in aqueous solution. The results indicate that the large planar amine ligands in the palladium complexes do not hinder formation of bifunctional adducts with DNA bases, and the rates for monofunctional and bifunctional binding to DNA bases to be larger than those of platinum-based agents.

Key words: Density functional theory, Purine base, Cytosine, Antitumor, Transition state

MSC2000: 

  • O641