以姜黄素衍生物为双配体的金属配合物的理论设计  

Theoretical Design and Study of Metal Complexes with Two Curcumin Derivatives as Ligands

作　　者：郭亚星 江珊 林清叶 孙伟明 GUO Yaxing;JIANG Shan;LIN Qingye;SUN Weiming(The Department of Basic Chemistry,School of Pharmacy,Fujian Medical University,Fuzhou 350122,China)

机构地区：[1]福建医科大学药学院基础化学系,福州350122

出　　处：《福建医科大学学报》2022年第3期187-194,共8页Journal of Fujian Medical University

基　　金：国家自然科学基金(21603032);福建医科大学大学生创新创业训练计划项目(202010392018)。

摘　　要：目的克服姜黄素水溶性差和生物利用率低的难题,对姜黄素进行结构修饰并设计双姜黄素配体金属化合物。方法在姜黄素结构中引入水溶性基团,通过量子化学计算和分子对接验证水溶性及其与靶点结合强度。将性能优异的L-羟基脯氨酸-姜黄素的阴离子作为配体L,与低毒性的Zn^(2+)和Cr^(2+)结合设计成双配体的ZnL_(2)和CrL_(2)配合物,并基于密度泛函理论(DFT)对其几何和电子结构性质进行系统研究。结果L-羟基脯氨酸-姜黄素具有负值最大的溶解能(-161.61 kJ/mol)和较大的对接打分(8.990)。设计的ZnL_(2)的结合能和Gap值分别高达601.85 kJ/mol和3.67 eV,均高于CrL_(2)。结论结构修饰显著提高了姜黄素衍生物的水溶性,且保留了姜黄素的抗肿瘤作用。ZnL_(2)较CrL_(2)具有更高的稳定性,其中Zn^(2+)与配体形成强极性共价键。Objective To overcome the challenges of poor water solubility and low bioavailability of curcumin,chemically modify the structure of curcumin,and use them as dual curcumin ligands to design new metal complexes.Methods Introduce water-soluble groups into curcumin,and verify the solubility and binding strength with target of curcumin derivatives through molecular docking and quantum chemical calculations.The anion of L-hydroxyproline-curcumin with excellent performance was used as ligand L to combine with low toxicity Zn^(2+)and Cr ^(2+)to design ZnL_(2) and CrL_(2) complexes with dual ligands.Their geometric and electronic structures were systematically studied by density functional theory(DFT).Results L-hydroxyproline-curcumin has the most negative solvation energy of-161.61 kJ/mol,and relatively large docking score(8.990).The binding energy and Gap value of ZnL_(2) are 601.85 kJ/mol and 3.67 eV,respectively,which are higher than those of CrL_(2).Conclusion The structural modification significantly improves the solubility of curcumin derivatives and retains the antitumor effect of curcumin.ZnL_(2) has higher stability than CrL_(2),in whcih Zn^(2+) forms strong polar covalent bonds with curcumin ligands.

关 键 词：姜黄素 抗癌药物 分子对接 金属配合物 密度泛函理论 

分 类 号：R284[医药卫生—中药学] O641.4[医药卫生—中医学]