Novel bimetallic oxido-bridged phenolato hafniumIV complex with enhanced anti-tumor activity and aqueous stability

A novel dimeric phenolato Hafnium complex [{HfIV(Salan2,4-Me)(OnBu)}2O] was synthesized by reacting [HfIV(Salan2,4-Me)2] in the presence of 100 equiv. of H2O. The structure was characterized by 1H, 13C NMR spectroscopy, HRMS and X-Ray diffraction. In comparison with [HfIV(Salan2,4-Me)2] and another precursor [{HfIV(Salan2,4-Me)(OnBu)}2O], this dimeric HfIV complex demonstrated enhanced aqueous stability and anti-tumor activity (IC50: 71.2 ± 25.3 μM against Hela S3 cells; 62.2 ± 27.7 μM against Hep G2 cells). Furthermore, this dimeric HfIV complex can only be synthesized from [HfIV(Salan2,4-Me)2] in low equivalent of H2O, upon addition of 2,6-dipicolinic acid, it can be transformed to a Salan/Dipic HfIV bis-chelated complex.