Bifunctional Mononuclear Dysprosium Complexes: Single-Ion Magnet Behaviors and Antitumor Activities

Two mononuclear dysprosium complexes (Et₃NH)[Dy(BrMQ)₄]·H₂O·DMF(BrMQ-Dy) and (Et₃NH)[Dy(ClMQ)₄]·H₂O·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_4d 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^a, ClMQ-Dy, and ClMQ-Dy^a are 47.8, 27.3, 96.0, and 65.5 cm^-1, respectively (BrMQ-Dy^a and ClMQ-Dy^a 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 IC₅₀ 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.