Synthesis and X-ray structure analysis of cytotoxic heptacoordinated Salan hafnium(IV) complexes stabilized with 2,6-dipicolinic acid

Four novel Salan Hf(IV) complexes stabilized by 2,6-dipicolinic acid (Dipic) were synthesized and characterized by 1H, 13C NMR and X-ray diffraction spectroscopy. These Hf(IV) bis-chelates could be obtained in good to excellent yields (88%-91%) and demonstrated rather good stability in aqueous media and on silica gel. [L2Hf(IV)Dipic4-H,Cl] containing steric bulk L2 were stable in about 10% H2O (H2O/THF (v/v)), however, [L1Hf(IV)Dipic4-H,Cl] with non-steric L1 could slowly dissociate and release nontoxic L1. [L1-2Hf(IV)Dipic4-Cl] showed excellent anti-tumoral activity in the range of cisplatin (Hela S3: IC50 = 3.5 +/- 0.4 mu M, Hep G2: IC50 = 11.2 +/- 2.1 mu M). In addition, the cellular uptake and apoptosis investigation of [L1Hf(IV)Dipic4-Cl] suggested a fast cellular uptake process against Hela S3 cells with an almost exclusive induced apoptosis cell death path.

Automated summary

Four novel Hf(IV) complexes stabilized by 2,6-dipicolinic acid (Dipic) were synthesized and characterized. These complexes demonstrated good stability in aqueous media and on silica gel. Among them, [L1-2Hf(IV)Dipic4-Cl] showed excellent anti-tumoral activity comparable to cisplatin.