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基于水杨醛的糠酸腙的钒(IV)配合物:合成、与牛血清白蛋白结合及体内抗糖尿病潜力

Vanadium(IV) complexes of salicylaldehyde-based furoic acid hydrazones: Synthesis, BSA binding and in vivo antidiabetic potential.

作者信息

Zahirović Adnan, Hadžalić Selma, Višnjevac Aleksandar, Fočak Muhamed, Tüzün Burak, Žilić Dijana, Roca Sunčica, Jurec Jurica, Topčagić Anela, Osmanković Irnesa

机构信息

Laboratory for Inorganic and Bioinorganic Chemistry, Department of Chemistry, Faculty of Science, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.

Laboratory for Inorganic and Bioinorganic Chemistry, Department of Chemistry, Faculty of Science, University of Sarajevo, Sarajevo, Bosnia and Herzegovina.

出版信息

J Inorg Biochem. 2023 Jul;244:112232. doi: 10.1016/j.jinorgbio.2023.112232. Epub 2023 Apr 15.

Abstract

Solution synthesis afforded five novel neutral heteroleptic octahedral paramagnetic mononuclear oxidovanadium(IV) complexes of general composition [VO(bpy)L], where L is a dianionic tridentate ONO-donor hydrazone ligand derived from 2-furoic acid hydrazide and salicylaldehyde and its 5-substituted derivatives. Characterization was carried out by elemental analysis, mass spectrometry, infrared, electron, NMR, and EPR spectroscopy, cyclic voltammetry and conductometry. The molecular and crystal structure of the complex with 5-chloro-salicylaldehyde 2-furoic acid hydrazone (2) was determined. The quantum chemical properties of the vanadium complexes were studied at B3LYP and M062X levels with the lanl2dz basis set using Gaussian. Additionally, Swiss-ADME analysis was performed and complex (4), featuring a 5-nitro substituent on the hydrazone ligand, was selected for further investigation. The effects of the in vivo application of the complex on selected biochemical parameters in healthy and diabetic Wistar rats were investigated. Strong antidiabetic effect associated with moderate hypoalbuminemia was observed. Furthermore, the interaction of complexes with BSA was studied by spectrofluorimetry. A significant conformational change of BSA in the presence of vanadium complexes was found. Synchronous fluorescence spectra revealed significant changes in the tyrosine microenvironment of BSA. The FRET analysis was also used and the non-radiative process of energy transfer is elucidated. Thermodynamic data suggest van der Waals forces and hydrogen bonding as predominant binding modes of complexes to BSA.

摘要

溶液合成得到了五种新型中性杂配八面体顺磁性单核氧化钒(IV)配合物,其通式为[VO(bpy)L],其中L是一种双齿三齿ONO供体腙配体,由2-呋喃甲酰肼和水杨醛及其5-取代衍生物衍生而来。通过元素分析、质谱、红外光谱、电子光谱、核磁共振光谱、电子顺磁共振光谱、循环伏安法和电导法进行表征。测定了5-氯水杨醛2-呋喃甲酰腙(2)配合物的分子和晶体结构。使用高斯软件在B3LYP和M062X水平上,采用lanl2dz基组研究了钒配合物的量子化学性质。此外,进行了瑞士药物代谢动力学分析,并选择了在腙配体上具有5-硝基取代基的配合物(4)进行进一步研究。研究了该配合物在健康和糖尿病Wistar大鼠体内应用对选定生化参数的影响。观察到与中度低白蛋白血症相关的强烈抗糖尿病作用。此外,通过荧光光谱法研究了配合物与牛血清白蛋白(BSA)的相互作用。发现钒配合物存在时BSA发生了显著的构象变化。同步荧光光谱显示BSA酪氨酸微环境有显著变化。还使用了荧光共振能量转移分析,并阐明了能量转移的非辐射过程。热力学数据表明范德华力和氢键是配合物与BSA结合的主要模式。

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