Koller Angus J, Wang Lilian, Deluca Molly, Glaser Owen, Robis Mariae J, Mixdorf Jason C, Chernysheva Margarita N, Guzei Ilia A, Aluicio-Sarduy Eduardo, Barnhart Todd E, Engle Jonathan W, Boros Eszter
Department of Chemistry, Stony Brook University, Stony Brook, New York 11794, United States.
Department of Medical Physics, University of Wisconsin, 1111 Highland Avenue, Madison, Wisconsin 53705, United States.
Inorg Chem. 2023 Dec 18;62(50):20655-20665. doi: 10.1021/acs.inorgchem.3c01493. Epub 2023 Jul 31.
The solution chemistry of the hydrolytic, early-transition-metal ions Ti and Sc represents a coordination chemistry challenge with important real-world implications, specifically in the context of Ti/Sc and Ti/Sc radiochemical separations. Unclear speciation of the solid and solution phases and tertiary mixtures of mineral acid, organic chelators, and solid supports are common confounds, necessitating tedious screening of multiple variables. Herein we describe how thermodynamic speciation data in solution informs the design of new solid-phase chelation approaches enabling separations of Ti and Sc. The ligands catechol (benzene-1,2-diol) and deferiprone [3-hydroxy-1,2-dimethyl-4(1)-pyridone] bind Ti at significantly more acidic conditions (2-4 pH units) than Sc. Four chelating resins were synthesized using either catechol or deferiprone with two different solid supports. Of these, deferiprone appended to carboxylic acid polymer-functionalized silica (CA-Def) resin exhibited excellent binding affinity for Ti across a wide range of HCl concentrations (1.0-0.001 M), whereas Sc was only retained in dilute acidic conditions (0.01-0.001 M HCl). CA-Def resin produced separation factors of >100 (Ti/Sc) in 0.1-0.4 M HCl, and the corresponding values (>1000) show strong retention of Ti. A model Ti/Sc generator was produced, showing 65 ± 3% yield of Sc in 200 μL of 0.2 M HCl with a significant Ti breakthrough of 0.1%, precluding use in its current form. Attempts, however, removed Sc in loading fractions and a dilute (0.4 M HCl) wash and recovered 80% of the loaded Ti activity in 400 μL of 6 M HCl. The previously validated Ti chelator TREN-CAM was used for comparative proof-of-concept reactions with the CA-Def eluent (in HCl) and literature-reported hydroxamate-based resin eluents (in citric acid). CA-Def shows improved radiolabeling efficiency with an apparent molar activity (AMA) of 0.177 mCi nmol, exceeding the established methods (0.026 mCi nmol) and improving the separation and recovery of Ti for positron emission tomography imaging applications.
水解性早期过渡金属离子钛（Ti）和钪（Sc）的溶液化学代表了一项配位化学挑战，具有重要的现实意义，特别是在Ti/Sc和Ti/Sc放射性化学分离的背景下。固相和溶液相以及无机酸、有机螯合剂和固相载体的三元混合物的物种形成不明确是常见的干扰因素，这使得必须对多个变量进行繁琐的筛选。在此，我们描述了溶液中的热力学物种形成数据如何为设计新的固相螯合方法提供信息，从而实现Ti和Sc的分离。儿茶酚（苯 - 1,2 - 二醇）和去铁酮[3 - 羟基 - 1,2 - 二甲基 - 4(1) - 吡啶酮]在比Sc明显更酸性的条件（pH值相差2 - 4个单位）下与Ti结合。使用儿茶酚或去铁酮与两种不同的固相载体合成了四种螯合树脂。其中，连接到羧酸聚合物功能化二氧化硅（CA - Def）树脂上的去铁酮在广泛的HCl浓度范围（1.0 - 0.001 M）内对Ti表现出优异的结合亲和力，而Sc仅在稀酸性条件（0.01 - 0.001 M HCl）下被保留。CA - Def树脂在0.1 - 0.4 M HCl中产生的分离因子>100（Ti/Sc），相应的 值（>1000）表明对Ti有很强的保留能力。制备了一个模拟Ti/Sc发生器，在200 μL的0.2 M HCl中Sc的产率为65 ± 3%，Ti有0.1%的显著穿透，因此目前形式无法使用。然而，通过在加载部分和稀（0.4 M HCl）洗涤中去除Sc，并在400 μL的6 M HCl中回收80%的加载Ti活度。先前经过验证的Ti螯合剂TREN - CAM用于与CA - Def洗脱液（在HCl中）和文献报道的基于异羟肟酸酯的树脂洗脱液（在柠檬酸中）进行比较概念验证反应。CA - Def显示出更高的放射性标记效率，表观摩尔活度（AMA）为0.177 mCi nmol，超过了既定方法（0.026 mCi nmol），并改善了用于正电子发射断层扫描成像应用的Ti的分离和回收。
