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研究两种水溶性单核镧(III)配合物的复杂结构、比较 DNA 结合和 DNA 切割以及壳聚糖包覆磁性纳米粒子作为药物载体的细胞毒性活性。

Investigation of the complex structure, comparative DNA-binding and DNA cleavage of two water-soluble mono-nuclear lanthanum(III) complexes and cytotoxic activity of chitosan-coated magnetic nanoparticles as drug delivery for the complexes.

机构信息

Department of Chemistry, Faculty of Sciences, Shiraz University, Shiraz 71454, Iran.

Department of Chemistry, Faculty of Sciences, Shiraz University, Shiraz 71454, Iran.

出版信息

Spectrochim Acta A Mol Biomol Spectrosc. 2017 May 5;178:125-135. doi: 10.1016/j.saa.2017.01.037. Epub 2017 Jan 21.

DOI:10.1016/j.saa.2017.01.037
PMID:28178588
Abstract

Two water-soluble mono-nuclear macrocyclic lanthanum(III) complexes of 2,6-diformyl-4-methylphenol with 1,3-diamino-2-propanol (C) or 1,3-propylenediamine (C) were synthesized and characterized by UV-Vis, FT-IR, C and H NMR spectroscopy and elemental analysis. C complex was structurally characterized by single-crystal X-ray diffraction, which revealed that the complex was mononuclear and ten-coordinated. The coordination sites around lanthanum(III) were occupied with a five-dentate ligand, two bidentate nitrates, and one water molecule. The interaction of complexes with DNA was studied in buffered aqueous solution at pH7.4. UV-Vis absorption spectroscopy, emission spectroscopy, circular dichroism (CD) and viscometric measurements provided clear evidence of the intercalation mechanism of binding. The obtained intrinsic binding constants (K) 9.3×10 and 1.2×10M for C and C, respectively confirmed that C is better intercalator than C. The DNA docking studies suggested that the complexes bind with DNA in a groove binding mode with the binding affinity of C>C. Moreover, agarose gel electrophoresis study of the DNA-complex for both compounds revealed that the C intercalation cause ethidium bromide replacement in a competitive manner which confirms the suggested mechanism of binding. Finally, the anticancer experiments for the treated cancerous cell lines with both synthesized compounds show that these hydrophilic molecules need a suitable carrier to pass through the hydrophobic nature of cell membrane efficiently.

摘要

两种水溶性单核大环镧(III)配合物,由 2,6-二醛基-4-甲基苯酚与 1,3-二氨基-2-丙醇(C)或 1,3-丙二胺(C)合成,并通过紫外可见光谱、傅里叶变换红外光谱、C 和 H 核磁共振光谱和元素分析进行了表征。C 配合物的结构通过单晶 X 射线衍射进行了表征,结果表明该配合物为单核和十配位。镧(III)周围的配位位被一个五齿配体、两个双齿硝酸盐和一个水分子占据。在 pH7.4 的缓冲水溶液中研究了配合物与 DNA 的相互作用。紫外可见吸收光谱、荧光光谱、圆二色性(CD)和粘度测量提供了结合的嵌入机制的明确证据。分别获得的固有结合常数(K)9.3×10 和 1.2×10M 对于 C 和 C,证实 C 是比 C 更好的嵌入剂。DNA 对接研究表明,配合物以沟结合模式与 DNA 结合,结合亲和力为 C>C。此外,两种化合物的 DNA-复合物的琼脂糖凝胶电泳研究表明,C 的嵌入以竞争性方式取代溴化乙锭,这证实了所建议的结合机制。最后,用两种合成化合物处理癌细胞系的抗癌实验表明,这些亲水分子需要合适的载体才能有效地穿过细胞膜的疏水性。

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