Zou Hua-Hong, Meng Ting, Chen Qi, Zhang Yi-Quan, Wang Hai-Ling, Li Bo, Wang Kai, Chen Zi-Lu, Liang Fupei
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources , School of Chemistry & Pharmacy of Guangxi Normal University , Yucai Road 15 , Guilin 541004 , People's Republic of China.
Jiangsu Key Laboratory for NSLSCS, School of Physical Science and Technology , Nanjing Normal University , Wenyuan Road 1 , Nanjing 210023 , People's Republic of China.
Inorg Chem. 2019 Feb 18;58(4):2286-2298. doi: 10.1021/acs.inorgchem.8b02250. Epub 2019 Jan 30.
Two mononuclear dysprosium complexes (EtNH)[Dy(BrMQ)]·HO·DMF(BrMQ-Dy) and (EtNH)[Dy(ClMQ)]·HO·DMF (ClMQ-Dy) (H-BrMQ = 5,7-dibromo-2-methyl-8-quinolinol, H-ClMQ = 5,7-dichloro-2-methyl-8-quinolinol) were synthesized and characterized. The Dy(III) ions in complexes BrMQ-Dy and ClMQ-Dy have a pseudo-D local symmetry. Magnetic characterizations reveal that complex BrMQ-Dy is a single-ion magnet and complex ClMQ-Dy exhibits field-induced slow magnetic relaxation behaviors. The calculated effective barriers of BrMQ-Dy, BrMQ-Dy, ClMQ-Dy, and ClMQ-Dy are 47.8, 27.3, 96.0, and 65.5 cm, respectively (BrMQ-Dy and ClMQ-Dy represent the desolvated samples of BrMQ-Dy and ClMQ-Dy, respectively). Ab initio calculations confirmed that coordination symmetry of the Dy(III) ions, electron-withdrawing ligands, and the guest molecules is a key factor affecting the magnetic dynamics of the two complexes. The IC values of BrMQ-Dy and ClMQ-Dy against BEL-7404, HeLa, and Hep-G2 cancer cells were 1.01-22.06 μM. Interestingly, two Dy(III) complexes were less toxic to normal HL-7702 cells. BrMQ-Dy and ClMQ-Dy significantly induced cell arrest at G2 phase and down-regulated the G2 phase-related protein levels. Various experiments suggested that BrMQ-Dy and ClMQ-Dy also caused dysfunction of mitochondrial pathways in HeLa cells. Taken together, the different in vitro anticancer activity of complexes BrMQ-Dy and ClMQ-Dy in the order of 5,7-dichloro substitution > 5,7-dibromo substitution.
合成并表征了两种单核镝配合物(EtNH)[Dy(BrMQ)]·H₂O·DMF(BrMQ-Dy)和(EtNH)[Dy(ClMQ)]·H₂O·DMF(ClMQ-Dy)(H-BrMQ = 5,7-二溴-2-甲基-8-喹啉醇，H-ClMQ = 5,7-二氯-2-甲基-8-喹啉醇)。配合物BrMQ-Dy和ClMQ-Dy中的Dy(III)离子具有伪D局部对称性。磁性表征表明，配合物BrMQ-Dy是一种单离子磁体，配合物ClMQ-Dy表现出场诱导的慢磁弛豫行为。计算得到的BrMQ-Dy、BrMQ-Dy、ClMQ-Dy和ClMQ-Dy的有效势垒分别为47.8、27.3、96.0和65.5 cm(BrMQ-Dy和ClMQ-Dy分别代表BrMQ-Dy和ClMQ-Dy的去溶剂化样品)。从头算计算证实，Dy(III)离子的配位对称性、吸电子配体和客体分子是影响这两种配合物磁动力学的关键因素。BrMQ-Dy和ClMQ-Dy对BEL-7404、HeLa和Hep-G2癌细胞的IC值为1.01-22.06 μM。有趣的是，两种Dy(III)配合物对正常HL-7702细胞的毒性较小。BrMQ-Dy和ClMQ-Dy显著诱导细胞在G2期停滞，并下调G2期相关蛋白水平。各种实验表明，BrMQ-Dy和ClMQ-Dy还导致HeLa细胞线粒体途径功能障碍。综上所述，配合物BrMQ-Dy和ClMQ-Dy的体外抗癌活性不同，顺序为5,7-二氯取代＞5,7-二溴取代。
