Palladium(Ⅱ)complexes coordinated to large planar amine ligands represent a lead stucture of considerable interest in current antitumor drug design.However,the question is whether these complexes call 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,PdCl_2L_2,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 anfitumor 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.%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-FCM)溶剂化模型研究了trans-PdCl_2L_2(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.
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