Aupiais J, Bonin L, Den Auwer C, Moisy P, Siberchicot B, Topin S
CEA, DAM, DIF, F-91297 Arpajon cedex, France.
CEA, DEN, DRCP, F-30207 Bagnols sur Cèze, France.
Dalton Trans. 2016 Mar 7;45(9):3759-70. doi: 10.1039/c5dt04104j.
In the case of an accidental nuclear event, contamination of human bodies by actinide elements may occur. Such elements have the particularity to exhibit both radiological and chemical toxicities that may induce severe damages at several levels, depending on the biokinetics of the element. In order to eliminate the actinide elements before they are stored in target organs (liver, kidneys, or bone, depending on the element), sequestering agents must be quickly injected. However, to date, there is still no ideal sequestering agent, despite the recent interest in this topic due to contamination concerns. DTPA (diethylene triamine pentaacetic acid) is currently generating interest for the development of oral or alternative self-administrable forms. Although biokinetics data are mostly available, molecular scale characterization of actinide-DTPA complexes is still scarce. Nevertheless, strong interest is growing in the characterization of An(IV)DTPA(-) complexes at the molecular level because this opens the way for predicting the stability constants of unknown systems or even for developing new analytical strategies aimed at better and more selective decorporation. For this purpose, Extended X-ray Absorption Fine Structure (EXAFS) and Ab Initio Molecular Dynamics (AIMD) investigations were undertaken and compared with capillary electrophoresis (CE) used in a very unusual way. Indeed, it is commonly believed that CE is incapable of extracting structural information. In capillary electrophoresis, the electrophoretic mobility of an ion is a function of its charge and size. Despite very similar ratios, partial separations between An(IV)DTPA(-) species (An(IV) = Th, U, Np, Pu) were obtained. A linear relationship between the electrophoretic mobility and the actinide--oxygen distance calculated by AIMD was evidenced. As an example, the interpolated U-O distances in U(IV)DTPA(-) from CE-ICPMS experiments, EXAFS, AIMD, and the relationship between the stability constants and the ratio z/dAn-O, are all in agreement. This results in the capability to evaluate the stability constants for the formation of Pa(IV)DTPA(-), Am(IV)DTPA(-) or Bk(IV)DTPA(-).
在发生意外核事件的情况下，人体可能会被锕系元素污染。这类元素具有特殊性，会同时表现出放射毒性和化学毒性，根据元素的生物动力学特性，可能会在多个层面造成严重损害。为了在锕系元素存储于靶器官（取决于元素种类，可能是肝脏、肾脏或骨骼）之前将其清除，必须迅速注射螯合剂。然而，尽管由于污染问题，近期对这一话题的关注度有所提高，但到目前为止，仍没有理想的螯合剂。二乙烯三胺五乙酸（DTPA）目前在口服或其他可自行给药形式的开发方面引起了关注。虽然大多已有生物动力学数据，但关于锕系元素 - DTPA络合物的分子尺度表征仍然很少。尽管如此，对An(IV)DTPA(-)络合物在分子水平上的表征兴趣日益浓厚，因为这为预测未知体系的稳定常数，甚至为开发旨在更好、更有选择性地促排的新分析策略开辟了道路。为此，开展了扩展X射线吸收精细结构（EXAFS）和从头算分子动力学（AIMD）研究，并与以一种非常特殊方式使用的毛细管电泳（CE）进行了比较。实际上，人们普遍认为CE无法提取结构信息。在毛细管电泳中，离子的电泳迁移率是其电荷和大小的函数。尽管比例非常相似，但仍实现了An(IV)DTPA(-)物种（An(IV) = 钍、铀、镎、钚）之间的部分分离。通过AIMD计算得到的电泳迁移率与锕系元素 - 氧距离之间的线性关系得到了证实。例如，通过CE - ICPMS实验、EXAFS、AIMD得到的U(IV)DTPA(-)中内插的U - O距离，以及稳定常数与z/dAn - O比值之间的关系，均相互吻合。这使得能够评估Pa(IV)DTPA(-)、Am(IV)DTPA(-)或Bk(IV)DTPA(-)形成时的稳定常数。
