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

• DOI: 10.1016/j.jinorgbio.2022.112094
• Publication Date: 2022-12-09T05:12:36Z
• Authors: Tiankun Zhao; Peng Wang; Nan Liu; Wenzhuo Zhao; Mingjun Yang; Shanjia Li; Zhongduo Yang; Bolu Sun; Thomas Huhn
• Keywords: X-Rays; Humans; Antineoplastic Agents; Picolinic Acids; Hafnium

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 μM, Hep G2: IC50 = 11.2 ± 2.1 μM). 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.