RESUMO
We previously reported the spin-crossover (SC) properties of [FeII(tacn)2](OTf)2 (1) (tacn = 1,4,7-triazacyclononane) [Eur. J. Inorg. Chem. 2013, 2115]. Upon heating under dynamic vacuum, 1 undergoes oxidation to generate a low spin iron(III) complex. The oxidation of the iron center was found to be facilitated by initial oxidation of the ligand via loss of an H atom. The resulting complex was hypothesized to have the formulation [FeIII(tacn)(tacn-H)](OTf)2 (2) where tacn-H is N-deprotonated tacn. The formulation was confirmed by ESI-MS. The powder EPR spectrum of the oxidized product at 77 K reveals the formation of a low-spin iron(III) species with rhombic spectrum (g = 1.98, 2.10, 2.19). We have indirectly detected H2 formation during the heating of 1 by reacting the headspace with HgO. Formation of water (1HNMR in anhydrous d6-DMSO) and elemental mercury were observed. To further support this claim, we independently synthesized [FeIII(tacn)2](OTf)3 (3) and treated it with one equiv base yielding 2. The structures of 3 was characterized by X-ray crystallography. Compound 2 also exhibits a low spin iron(III) rhombic signal (g = 1.97, 2.11, 2.23) in DMF at 77 K. Variable temperature magnetic susceptibility measurements indicate that 3 undergoes gradual spin increase from 2 to 400 K. DFT studies indicate that the deprotonated nitrogen in 2 forms a bond to iron(III) exhibiting double bond character (Fe-N, 1.807 Å).
RESUMO
Histiotrophic nutrition pathways (HNPs) are processes by which the organogenesis-stage conceptus obtains nutrients, amino acids, vitamins and cofactors required for protein biosynthesis and metabolic activities. Nutrients are captured from the maternal milieu as whole proteins and cargoes via receptor-mediated endocytosis in the visceral yolk sac (VYS), degraded by lysosomal proteolysis and delivered to the developing embryo (EMB). Several nutrients obtained by HNPs are required substrates for one-carbon (C1) metabolism and supply methyl groups required for epigenetic processes, including DNA and histone methylation. Increased availability of methyl donors has been associated with reduced risk for neural tube defects (NTDs). Here, we show that mono-2-ethylhexyl phthalate (MEHP) treatment (100 or 250µM) alters HNPs, C1 metabolism and epigenetic programming in the organogenesis-stage conceptus. Specifically, 3-h MEHP treatment of mouse EMBs in whole culture resulted in dose-dependent reduction of HNP activity in the conceptus. To observe nutrient consequences of decreased HNP function, C1 components and substrates and epigenetic outcomes were quantified at 24h. Treatment with 100-µM MEHP resulted in decreased dietary methyl donor concentrations, while treatment with 100- or 250-µM MEHP resulted in dose-dependent elevated C1 products and substrates. In MEHP-treated EMBs with NTDs, H3K4 methylation was significantly increased, while no effects were seen in treated VYS. DNA methylation was reduced in MEHP-treated EMB with and without NTDs. This research suggests that environmental toxicants such as MEHP decrease embryonic nutrition in a time-dependent manner and that epigenetic consequences of HNP disruption may be exacerbated in EMB with NTDs.