Jaraquemada-Peláez María de Guadalupe, Wang Xiaozhu, Clough Thomas J, Cao Yang, Choudhary Neha, Emler Kirsten, Patrick Brian O, Orvig Chris
Medicinal Inorganic Chemistry Group, Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada.
Dalton Trans. 2017 Oct 31;46(42):14647-14658. doi: 10.1039/c7dt02343j.
Hoctapa is an extremely versatile acyclic chelator for a wide variety of medicinally relevant metal ions, forming complexes of both high thermodynamic and kinetic stability. This work reports a significantly simplified 3 step high yield straightforward synthesis of Hoctapa directly from EDDA. Crystals of the octa-protonated form of the ligand [Hoctapa] as its tetrachloride salt, and of the mixed lanthanum-sodium salt of [La(octapa)] were isolated and characterized by X-ray diffraction. All eight protonation constants for the ligand were determined through combined potentiometric-spectrophotometric titrations and in batch experiments using UV spectrophotometry and H NMR spectroscopy. Synthesis, characterisation and solution equilibria studies are presented for complexes [Ln(octapa)] (Ln = lanthanide element) with Sm(iii), Dy(iii), and Yb(iii) (each of which have radiopharmaceutical applications). Complex formation equilibria studies provided evidence of Ln(Hoctapa), [Ln(octapa)] and [Ln(octapa)(OH)] species in solution, and their stability constants were evaluated by pH-potentiometric competition titrations using [ttha] as a competing ligand, and by UV-vis spectrophotometric measurements. The high stability constants of the [Ln(octapa)] complexes with Sm(iii), Dy(iii), and Yb(iii) (log K = 20.10(2), log K = 20.14(3) and log K = 19.90(1)) are similar to the published values for other lanthanides and consequently these initial investigations confirm Hoctapa as a valuable ligand for Sm(iii), Dy(iii), Yb(iii) and other Ln for application in diagnostic and therapeutic nuclear medicine.
Hoctapa是一种极其通用的无环螯合剂，可用于多种与医学相关的金属离子，能形成具有高热力学稳定性和动力学稳定性的配合物。本工作报道了一种从EDDA直接合成Hoctapa的显著简化的三步高产率直接合成法。分离出了配体[Hoctapa]八质子化形式的四氯化物盐晶体以及[La(octapa)]的镧 - 钠盐晶体，并通过X射线衍射对其进行了表征。通过电位 - 分光光度联合滴定以及使用紫外分光光度法和核磁共振氢谱的批量实验，测定了该配体的所有八个质子化常数。本文介绍了[Ln(octapa)]（Ln = 镧系元素）与Sm(iii)、Dy(iii)和Yb(iii)（它们各自都有放射性药物应用）配合物的合成、表征及溶液平衡研究。配合物形成平衡研究证明了溶液中存在Ln(Hoctapa)、[Ln(octapa)]和[Ln(octapa)(OH)]物种，并通过使用[ttha]作为竞争配体的pH电位竞争滴定以及紫外 - 可见分光光度测量评估了它们的稳定常数。[Ln(octapa)]与Sm(iii)、Dy(iii)和Yb(iii)配合物的高稳定常数（log K = 20.10(2)，log K = 20.14(3)和log K = 19.90(1)）与其他镧系元素的已发表值相似，因此这些初步研究证实Hoctapa是一种有价值的配体，可用于Sm(iii)、Dy(iii)、Yb(iii)以及其他镧系元素，应用于诊断和治疗核医学。
