氨基硫脲芳基钌配合物与人血清白蛋白的相互作用机制研究

doi:10.3964/j.issn.1000-0593(2023)09-2761-07

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摘要：氨基硫脲过渡金属配合物的生物学应用是当前研究的热点，为更好地了解氨基硫脲芳基钌配合物与人血清白蛋白（HSA）之间相互作用机制，合成了两种氨基硫脲芳基钌（Ⅱ）配合物，采用时间分辨荧光光谱法和稳态荧光光谱法研究了两种氨基硫脲芳基钌配合物与人血清白蛋白的荧光猝灭机理。荧光光谱结果表明，这两种氨基硫脲芳基钌配合物能使HSA的内源荧光猝灭，且HSA的荧光猝灭影响与配合物的浓度呈线性关系，通过对比发现配合物2对HSA的荧光猝灭效率更强。两个配合物与HSA相互作用的猝灭常数和结合常数均随温度的升高而降低，因此，配合物与HSA的相互作用是静态猝灭过程，且配合物2的荧光猝灭能力更强。通过热力学参数分析发现这两种配合物与HSA的主要结合作用力均为氢键和范德华力，且两种配合物与HSA之间的结合过程是自发进行的。最后采用红外吸收光谱及圆二色光谱验证了这两种氨基硫脲芳基钌配合物均对HSA二级构象产生了不同程度的影响，红外吸收光谱结果表明两种配合物与HSA的结合引起了HSA二级结构的重排，圆二色光谱结果表明这两种配合物的加入使HSA的二级结构稳定性降低。研究表明：通过探究氨基硫脲芳基钌配合物对人血清白蛋白结构和功能的影响，可揭示其作为抗肿瘤药物进入体内后与HSA的可能作用机制，从而为以氨基硫脲为配体的芳基钌配合物类抗肿瘤药物的研发提供理论参考。

关键词：氨基硫脲；芳基钌；人血清白蛋白；相互作用

Abstract：The biological application of thiosemicarbazide transition metal complexes is the focus of current research. In order to better understand the interaction mechanism between thiosemicarbazide aryl ruthenium complexes and has, two thiosemicarbazide aryl ruthenium（Ⅱ） complexes were synthesized. The fluorescence quenching mechanism of two thiosemicarbazide aryl ruthenium complexes with human albumin was studied by time-resolved fluorescence spectroscopy and steady-state fluorescence spectroscopy. Fluorescence spectroscopy results indicate that these two thiosemicarbazide aryl ruthenium complexes could quench the endogenous fluorescence of has, and the fluorescence quenching effect of HSA was linear with the concentration of the complex. It was found that the fluorescence quenching efficiency of complex 2 was stronger. The quenching and binding constants of the two complexes interacting with HSA decrease with the increase in temperature. Therefore, the interaction process between the complexes and HSA was a static quenching process, and the fluorescence quenching ability of complex 2 was stronger. Through the analysis of thermodynamic parameters, the main binding forces between the two complexes and HSA are hydrogen bond, and van der Waals force, and the binding process between the two complexes and HSA was spontaneous. Finally, the infrared absorption and circular dichroism spectra show that the two thiosemicarbazide aryl ruthenium complexes have different effects on the secondary conformation and microenvironment of HSA. The infrared absorption spectra show that combining the two complexes with HSA causes the rearrangement of the secondary structure of HSA, Circular dichroism spectra showed that the addition of these two complexes reduced the secondary structure stability of HSA. The above studies show that exploring the effect of thiosemicarbazide aryl ruthenium complex on the structure and function of human serum albumin can reveal its possible mechanism of action with HSA after entering the body as an antitumor drug. Therefore, it provides a theoretical reference for researching and developing aryl ruthenium complex anti-tumor drugs with thiosemicarbazide as the ligand.

Key words：Thiosemicarbazide;Ruthenium;Human serum albumin;Interaction

收稿日期: 2021-10-23 修订日期: 2022-11-20

中图分类号:

O675.3

基金资助: 国家自然科学基金地区基金项目（21463009），广西自然科学基金项目（2021GXNSFAA075015）和广西壮族自治区研究生创新计划项目（YCSW2019181）资助

通讯作者: 韦良，肖琦 E-mail: qi.xiao@nnnu.edu.cn; weil@nnnu.edu.cn

作者简介: 杨晶，女，1981年生，南宁师范大学化学与材料学院副教授 e-mail: yangjing1512F@126.com

引用本文:

杨晶，李莉，梁健丹，黄珊，苏炜，韦雅淑，韦良，肖琦. 氨基硫脲芳基钌配合物与人血清白蛋白的相互作用机制研究[J]. 光谱学与光谱分析, 2023, 43(09): 2761-2767.
YANG Jing, LI Li, LIANG Jian-dan, HUANG Shan, SU Wei, WEI Ya-shu, WEI Liang, XIAO Qi. Study on the Interaction Mechanism Between Thiosemicarbazide Aryl Ruthenium Complexes and Human Serum Albumin. SPECTROSCOPY AND SPECTRAL ANALYSIS, 2023, 43(09): 2761-2767.

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