Tales of the Unexpected: The Case of Zirconium(IV) Complexes with Desferrioxamine
Tales of the Unexpected: The Case of Zirconium(IV) Complexes with Desferrioxamine
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DOI：
10.3390/molecules24112098
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发表时间：
2019-06-01
期刊：
影响因子：
4.6
通讯作者：
Bianchi, Antonio
中科院分区：
文献类型：
--
作者：
Savastano, Matteo;Bazzicalupi, Carla;Bianchi, Antonio
去铁胺(H3DFO)及其衍生物的锆络合物是迄今为止用于质子发射断层扫描(PET)的唯一一种基于Zr-89的显像剂，目前已用于临床试验。然而，有关化合物的稳定常数尚不清楚，尚未对其在溶液中的完全形态形成进行过研究。本文首次用电位滴定法测定了该体系在水中的形态，并测定了在pH 2.5-11.5范围内形成的所有络合物的稳定常数。令人惊讶的是，尽管去铁胺与Zr4+形成了非常稳定的1：1络合物(对于Zr4++DFO-=[ZrDFO](+)，logK=36.14)，但在溶液中也形成了2：2和2：3的络合物。根据条件的不同，这些双核络合物可能是溶液中的主要物种。这些结果得到了复杂溶液的小角X射线散射(SAXS)和MALDI质谱分析的证实。通过密度泛函理论(DFT)计算获得了关于复杂结构的信息。
The Zr4+ complexes with desferrioxamine (H3DFO) and its derivatives are the only Zr-89-based imaging agents for proton emission tomography (PET) that have been used so far in clinical trials. Nevertheless, a complete speciation of the Zr4+/H3DFO system in solution has never been performed and the stability constants of the relevant complexes are still unknown. Here we report, for the first time, the speciation of this system in water, performed by potentiometric titrations, and the determination of the stability constants of all complexes formed in the pH range 2.5-11.5. Surprisingly, although desferrioxamine gives rise to very stable 1:1 complexes with Zr4+ (logK = 36.14 for Zr4+ + DFO3- = [ZrDFO](+)), 2:2 and 2:3 ones are also formed in solution. Depending on the conditions, these binuclear complexes can be main species in solution. These results were corroborated by small-angle X-ray scattering (SAXS) and MALDI mass spectrometry analyses of complex solutions. Information on complex structures was obtained by means of density functional theory (DFT) calculations.