Manipulating Fe(II) spin states to achieve higher anti-tumor cell activities in multinuclear complexes

Exploring the different spin states of central metals in the complex to regulate the anti-tumor activity of cancer cells is of great significance in drug design and clinical use. However, it is a challenge to build a strong coupling between spin states and anti-tumor activities in one system. Herein, we present two complexes {Fe^II₂L₂[Pd^II(CN)₄]₂}·2H₂O (L = Bztpen (1), Bztppn (2); Bztpen = N-benzyl-N,N',N'-tris(2-pyridylmethyl)ethylenediamine, Bztppn = N-benzyl-N,N',N'-tris(2-pyridylmethyl)propylenediamine) showing different cytotoxic activities actuated by fine-tuning the structure with different spin states of Fe(II). Magnetic susceptibility measurements and X-ray diffraction revealed that the Fe(II) ion in complexes 1 and 2 remains in the LS and HS state, respectively, at room temperature. Cytotoxicity tests indicate that complex 1 is more biologically effective than complex 2. In complex 2, however, the high-spin Fe(II) played a key role in regulating its in vitro antitumor effects and seems to be associated with ROS-mediated apoptosis. These findings offer a new avenue for developing anti-cancer drugs by designing complexes with different spin states.