稀土华法林阿魏酸三元配合物的制备及抗凝血作用

doi:10.7503/cjcu20150015

摘要/Abstract

摘要：

用华法林(W)、阿魏酸(FA)与La, Nd, Ce, Eu的稀土硝酸盐反应合成了4个三元稀土配合物, 并用红外光谱、热重分析、元素分析、 X射线粉末衍射和核磁共振波谱等方法对配合物进行了表征, 确定了三元配合物的组成. 在生理条件下测试了该三元配合物的全血凝血时间(CT)、复钙时间(RT)、活化部分凝血活酶时间(APTT)、凝血酶原时间(PT)和生物相容性, 并与稀土华法灵、稀土阿魏酸二元配合物及配体的抗凝血性质进行了比较. 结果表明, 4个三元稀土配合物均具有比二元配合物和配体更好的抗凝血性质. 生物相容性实验结果表明4个配合物对人肝癌细胞(HepG2)、人肺癌细胞(A549)和人宫颈癌细胞(HeLa)的活性无明显影响. 通过荧光光谱、紫外光谱和圆二色谱考察了三元配合物与人血清白蛋白(HSA)之间的相互作用. 结果表明, 配合物可以与HSA相互结合从而增强药物的血溶性, 避免了阿魏酸被氧化而失去原有的药效.

关键词: 稀土, 华法林, 阿魏酸, 抗凝血性质, 人血清白蛋白

Abstract:

Four ternary rare earth complexes of warfarin(W) and freulic acid(FA), RE(C₁₉H₁₅O₄)₂·(C₁₀H₉O₄)·2H₂O(RE=La, Nd, Ce, Eu), were obtained via the reaction of ferulic acid and warfarin with rare earth ions in the ethanol solution by solvent-thermal method. The composition of these complexes was characterized by infrared(IR) spectrometry, thermogravimetric-differential thermal analysis(TG-DTA), elemental analysis, X-ray diffraction(XRD) analysis and nuclear magnetic resonance(NMR) spectrometry. Meanwhile, the anticoagulant properties of warfarin, ferulic acid and their complexes were tested by coagulation time(CT), recalcification time(RT), activated partial thromboplastin time(APTT) and prothrombin time(PT) in physiological conditions. The results show that the four ternary rare earth complexes all have better anticoagulant action than the binary complexes of ferulic acid and warfarin in related anticoagulant experiments. The four ternary rare earth complexes could reduce the fluorescence intensity and enhance the UV intensity of human serum albumin(HSA).

Key words: Rare earth, Warfarin, Ferulic acid, Anticoagulant property, Human serum albumin(HSA)

中图分类号:

0614.33

TrendMD:

杨美玲, 秦冬冬, 宋玉民. 稀土华法林阿魏酸三元配合物的制备及抗凝血作用. 高等学校化学学报, 2015, 36(5): 821.

YANG Meiling, QIN Dongdong, SONG Yumin. Syntheses and Anticoagulant Action of Rare Earth Ternary omplexes with Warfarin and Ferulic Acid^†. Chem. J. Chinese Universities, 2015, 36(5): 821.

图/表 15

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Complex	Found(Calcd.)(%)			Λ/(S·cm²·mol^-1)
Complex	C		H	RE
FA-W-La	49.96(49.66)	5.30(5.10)	14.93(14.15)	29.3
FA-W-Ce	46.88(46.43)	5.53(5.02)	15.68(14.23)	27.4
FA-W-Nd	46.01(46.44)	5.75(5.03)	16.04(14.58)	19.6
FA-W-Eu	49.20(49.43)	4.11(4.53)	17.36(15.27)	18.4

Complex	Found(Calcd.)(%)			Λ/(S·cm²·mol^-1)
Complex	C		H	RE
FA-W-La	49.96(49.66)	5.30(5.10)	14.93(14.15)	29.3
FA-W-Ce	46.88(46.43)	5.53(5.02)	15.68(14.23)	27.4
FA-W-Nd	46.01(46.44)	5.75(5.03)	16.04(14.58)	19.6
FA-W-Eu	49.20(49.43)	4.11(4.53)	17.36(15.27)	18.4

Parameter	W-FA-La	W-FA-Nd	W-FA-Ce	W-FA-Eu
β	0.9624	0.9790	0.9644	0.9819
b^1/2	0.1371	0.1025	0.1334	0.0951
δ	3.9	2.1	3.6	1.8

Parameter	W-FA-La	W-FA-Nd	W-FA-Ce	W-FA-Eu
β	0.9624	0.9790	0.9644	0.9819
b^1/2	0.1371	0.1025	0.1334	0.0951
δ	3.9	2.1	3.6	1.8

Compound	Concentration/(mol·L^-1)	CT/min	P
Blank	0	4	<0.05
FA	2.0×10^-4	6	<0.05
W	2.0×10^-4	7	<0.05
W-La^a	2.5×10^-4	11.0	<0.05
W-Nd^a	2.5×10^-4	13.0	<0.05
W-Eu^a	2.5×10^-4	9.5	<0.05
W-Y^a	2.5×10^-4	8.8	<0.05
FA-Nd^b	2.5×10^-4	13.4	<0.05
FA-Ce^b	2.5×10^-4	11.3	<0.05
FA-Eu^b	2.5×10^-4	11.9	<0.05
W-FA-La	2.0×10^-4	25	<0.05
W-FA-Nd	2.0×10^-4	44	<0.05
W-FA-Ce	2.0×10^-4	40	<0.05
W-FA-Eu	2.0×10^-4	42	<0.05