4.6 Article

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

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JOURNAL OF INORGANIC BIOCHEMISTRY
卷 240, 期 -, 页码 -

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ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2022.112094

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Hafnium complexes; Anti-tumoral activity; Aqueous stability; Cellular uptake; Apoptosis; 6-dipicolinic acid

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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.
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.

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