کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1317018 | 976499 | 2008 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Influence of ligand structure on Fe(II) spin-state and redox rate in cytotoxic tripodal chelators Influence of ligand structure on Fe(II) spin-state and redox rate in cytotoxic tripodal chelators](/preview/png/1317018.png)
The Fe coordination chemistry of several tripodal aminopyridyl hexadentate chelators is reported along with cytotoxicity toward cultured Hela cells. The chelators are based on cis, cis-1,3,5-triaminocyclohexane (tach) with three pendant –CH2–2-pyridyl groups where 2-pyridyl is R-substituted thus are named tach-x-Rpyr where x = 3, R = Me; x = 3, R = MeO; x = 6; R = Me. The structures of [Fe(tach-3-Mepyr)]Cl2 and [Fe(tach-3-MeOpyr)](FeCl4) are reported and their metric parameters indicate strongly bound, low-spin Fe(II). The structure of [Fe(tach-6-Mepyr)](ClO4)2 implies steric effects of 6-Me groups push donor Npy’s away so one Fe–Npy bond is substantially longer at 2.380(3) Å vs. 2.228(3) Å for the others, and Fe(II) in the high-spin-state. Accordingly, anions X− = Cl or SCN afford [Fe(tach-6-Mepyr)(X)]+ from [Fe(tach-6-Mepyr)]2+ (UV–vis spectroscopy). Consistent with a biological cytotoxicity involving Fe chelation, chelators of low-spin Fe(II) have greater toxicity in the order [IC50(72 h) is in parentheses then the spin-state SS = H (high) or L (low)]: tachpyr = tach-3-Mepyr (6 μM, SS = L) ≳ tach-3-MeOpyr (12 μM, SS = L) ≫ tach-6-Mepyr (>200 μM, SS = H). Iron-mediated oxidative dehydrogenation with O2 oxidant removes hydrogens from coordinated nitrogen and the adjacent CH2, converting aqueous [Fe(tach-3-Rpyr)]2+ (R = H, Me and MeO) into a mix of low-spin imino- and aminopyridyl-armed complexes, but [Fe(tach-6-Mepyr)]2+ does not react (NMR and ESI-MS spectroscopies). The difference of IC50 for chelators at different time points (ΔIC50 = [IC50(24 h) − IC50(72 h)]) is used to compare rate of cytotoxic action to qualitative rate of oxidation in the Fe-bound chelator, giving the order, from rapid to slow oxidation and cell killing of: [Fe(tach-3-Mepyr)]2+ (ΔIC50 = 5 μM) > [Fe(tachpyr)]2+ (ΔIC50 = 16 μM) > [Fe(tach-3-MeOpyr)]2+ (ΔIC50 = 118 μM). Thus, those chelators whose Fe(II) complexes undergo rapid oxidation kill cells faster, and those that bind Fe(II) as low-spin are far more cytotoxic.
Journal: Journal of Inorganic Biochemistry - Volume 102, Issue 1, January 2008, Pages 150–156