Al(desferrioxamin B(-2H))(1+) | 156188-04-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环庚烷
• 英文名称: Al(desferrioxamin B(-2H))(1+)
• 英文别名: aluminoxamine
• CAS: 156188-04-4
• 化学式: C₂₅H₄₅AlN₆O₈*H
• 分子量: 585.657
• InChiKey: GCUHKFGWRMNHCE-UHFFFAOYSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  None
• 重原子数：
  None
• 可旋转键数：
  None
• 环数：
  None
• sp3杂化的碳原子比例：
  None
• 拓扑面积：
  None
• 氢给体数：
  None
• 氢受体数：
  None

反应信息

• 作为产物：
  描述：

  aluminum chloride hexahydrate 、 甲磺酸去铁敏 在 sodium hydroxide 、 hydrochloric acid 作用下， 以 水 为溶剂， 生成 Al(desferrioxamin B(-2H))(1+)
  参考文献：
  名称：

  X-ray Absorption Spectroscopy of Aqueous Aluminum-Organic Complexes

  摘要：

  Aqueous-phase X-ray absorption near-edge structure (XANES) spectra were collected on dissolved Al complexes with organic ligands, including desferrioxamine B, EDTA, acetohydroxamate, malate, oxalate, and salicylate. Spectral interpretations were made using the density functional theory-based modeling package StoBe. The goals of this work were to study the geometric and electronic structural characteristics of these complexes relative to Al(H2O)(6)(3+) and to examine the utility of the aqueous Al XANES technique as a tool for probing Al speciation and structure. In the case of EDTA, aqueous Fourier-transform infrared spectroscopy was also used to corroborate the structures of the Al(EDTA)(-) and AlOH(EDTA)(2-) complexes. Synthetic XANES spectra calculated with StoBe reproduced the observed spectral differences between Al(H2O)(6)(3+), Al(dfoB)(+), and Al(EDTA)(-). The narrower XANES feature observed for Al(dfoB)(+) relative to Al(H2O)(6)(3+) can be attributed to a weaker splitting of the Al 3p - O 2p interactions in the former, while Al(EDTA)(-) exhibits split Al 3p - ligand interactions that likely result from the mixed O/N coordination. In complexes with mixed aqua/organic-oxygen ligation (Al-acetohydroxamate, Al-malate, Al-oxalate, and Al-salicylate), spectra exhibit linear, systematic changes in peak width as a function of H2O to organic ligand ratio in the Al coordination sphere. These results highlight the sensitivity of the aqueous Al K-edge XANES spectrum to coordination environment and demonstrate its utility as an experimental probe for future studies of Al speciation in complex solutions.

  DOI：

  10.1021/jp909656q

文献信息

• Quantifying Intranasally Administered Deferoxamine in Rat Brain Tissue with Mass Spectrometry
  作者：Jacob Kosyakovsky、Bruce A. Witthuhn、Aleta L. Svitak、William H. Frey、Leah R. Hanson、Jared M. Fine

  DOI：10.1021/acschemneuro.9b00436

  日期：2019.11.20

  Deferoxamine, a metal chelator, has been shown to be neuroprotective in animal models of ischemic stroke, traumatic brain injury and both subarachnoid and intracerebral hemorrhage. Intranasal deferoxamine (IN DFO) has also shown promise as a potential treatment for multiple neurodegenerative diseases, including Parkinson's and Alzheimer's. However, there have been no attempts to thoroughly understand the dynamics and pharmacokinetics of IN DFO. We developed a new high-performance liquid-chromatography electrospray-tandem mass spectrometry (HPLC/ESI-MS2) method to quantify the combined total levels of DFO, ferrioxamine (FO; DFO bound to iron), and aluminoxamine (AO; aluminum-bound DFO) in brain tissue using a custom-synthesized deuterated analogue (DFO-d(7), Medical Isotopes Inc., Pelham NH) as an internal standard. We applied our method toward understanding the pharmacokinetics of IN DFO delivery to the brain and blood of rats from 15 min to 4 h after delivery. We found that IN delivery successfully targets DFO to the brain to achieve concentrations of 0.5-15 mu M in various brain regions within 15 min, and decreasing though still detectable after 4 h. Systemic exposure was minimized as assessed by concentration in blood serum. Serum concentrations were 0.02 mu M at 15 min and no more than 0.1 mu M at later time points. Compared to blood serum, brain region-specific drug exposure (as measured by area under the curve) ranged from slightly under 10 times exposure in the hippocampus to almost 200 times exposure in the olfactory bulb with IN DFO delivery. These findings represent a major step toward future method development, pharmacokinetic studies, and clinical trials for this promising therapeutic.