新型钳型钌(iii)配合物的合成及生物活性研究

Ana Rilak Simović, D. Lazić, Milica Međedović, D. Ćoćić, B. Petrović
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摘要

采用元素分析、红外光谱、紫外-可见光谱、质谱(MS)等方法合成了钌(III)螯合物[RuCl3(H2Lt-Bu] (H2Lt-Bu = 2,6-二(5-叔丁基- 1h -吡唑-3-基)吡啶1),并对其进行了表征。为了比较,我们还研究了通式[Ru(N-N-N)Cl3]的钌(III)三联吡啶配合物,其中N-N-N = 4′-氯-三联吡啶(Cl-tpy;2)或4′-氯基三联吡啶(Cl-Ph-tpy;3) 1-3与生物分子取代反应的动力学研究表明,速率常数取决于旁观配体的性质和进入的亲核试剂的性质。为了进一步了解钌配合物与潜在生物靶点的反应性,我们研究了1 - 3与DNA和HSA的相互作用。DNA/HSA结合研究表明,与配合物1(双吡唑基吡啶)相比,另外两个(2和3)三联吡啶配合物对小牛胸腺DNA (CT DNA)的结合亲和力略好,而对于人血清白蛋白(HSA),配合物1表现出最强的猝灭能力。
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SYNTHESIS AND BIOLOGICAL ACTIVITY OF THE NEW PINCER TYPE RUTHENIUM(III) COMPLEX
We synthesized and characterized the ruthenium(III) pincer-type complex [RuCl3(H2Lt-Bu] (H2Lt- Bu = 2,6-bis(5-tert-butyl-1H-pyrazol-3-yl)pyridine, 1) by elemental analysis, IR and UV-Vis spectroscopy, and mass spectrometry (MS) method ESI Q-TOF. For comparison reason, we also studied ruthenium(III) terpyridine complexes of the general formula [Ru(N-N-N)Cl3] where N-N-N = 4′-chloro- terpyridine (Cl-tpy; 2) or 4′-chlorophenyl-terpyridine (Cl-Ph-tpy; 3). Kinetic study of the substitution reactions of 1–3 with biomolecules showed that the rate constants depend on the properties of the spectator ligand and the nature of the entering nucleophile. To gain further insight into the reactivity of ruthenium complexes with potential biological targets, we examined the interactions of 1 – 3 with DNA and HSA. The DNA/HSA binding study showed that in comparison to complex 1 (bis– pyrazolylpyridine), the other two (2 and 3) terpyridine complexes had a slightly better binding affinity to calf thymus DNA (CT DNA), while in the case of human serum albumin (HSA), complex 1 exhibited the most strong quenching ability.
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