Noncovalent Interactions between a Trinuclear Monofunctional Platinum Complex and Human Serum Albumin

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• 作者：Yanqing Wang ; Xiaoyong Wang ; Jing Wang ; Yongmei Zhao ; Weijiang He ; Zijian Guo
• 刊名：Inorganic Chemistry
• 出版年：2011
• 出版时间：December 19, 2011
• 年：2011
• 卷：50
• 期：24
• 页码：12661-12668
• 全文大小：546K
• 年卷期：v.50,no.24(December 19, 2011)
• ISSN：1520-510X

文摘

Interactions between platinum complexes and human serum albumin (HSA) play crucial roles in the metabolism, distribution, and efficacy of platinum-based anticancer drugs. Polynuclear monofunctional platinum(II) complexes represent a new class of anticancer agents that display distinct molecular characters of pharmacological action from those of cisplatin. In this study, the interaction between a trinuclear monofunctional platinum(II) complex, [Pt₃LCl₃](ClO₄)₃ (L = N,N,N鈥?N鈥?N鈥?N鈥?hexakis(2-pyridylmethyl)-1,3,5-tris(aminomethyl)benzene) (1), and HSA was investigated using ultraviolet鈥搗isible spectroscopy, Fourier transform infrared spectroscopy, circular dichroism spectroscopy, fluorescence spectroscopy, molecular docking, and inductively coupled plasma mass spectrometry. The spectroscopic and thermodynamic data show that the interaction is a spontaneous process with the estimated enthalpy and entropy changes being 14.6 kJ mol^鈥? and 145.5 J mol^鈥? K^鈥?, respectively. The reactive sites of HSA to complex 1 mainly locate within its hydrophobic cavity in domain II. Noncovalent actions such as 蟺鈥撓€ stacking and hydrophobic bonding are the primary contributors to the interaction between HSA and complex 1, which is different from the scenario for cisplatin in similar conditions. The results suggest that the connection between complex 1 and HSA is reversible, and therefore the cytotoxic activity of the complex could be preserved during blood circulation.