Werner Eric J, Kozhukh Julia, Botta Mauro, Moore Evan G, Avedano Stefano, Aime Silvio, Raymond Kenneth N
Department of Chemistry, University of California, Berkeley, California 94720-1460, USA.
Inorg Chem. 2009 Jan 5;48(1):277-86. doi: 10.1021/ic801730u.
Four new Gd(III) complexes based on the 1,2-hydroxypyridinone chelator have been synthesized and evaluated as potential magentic resonance imaging contrast agents. Previously reported work examining Gd-TREN-1,2-HOPO (3; HOPO = hydroxypyridinone) suggests that the 1,2-HOPO unit binds strongly and selectively to Gd(III), encouraging further study of the stability and relaxivity properties of this class of compounds. Among the new complexes presented in this paper are the homopodal Gd-Ser-TREN-1,2-HOPO (Gd-5) and three heteropodal bis-1,2-HOPO-TAM complexes (Gd-6, Gd-7, and Gd-8; TAM = terephthalamide). Conditional stability constants were determined, and all pGd values are in the range of 18.5-19.7, comparable to other analogous HOPO complexes and currently used commercial contrast agents. Relaxivities for all complexes are about twice those of commercial agents, ranging from 7.8 to 10.5 mM(-1) s(-1) (20 MHz; 25 degrees C), and suggest two innersphere water molecules in fast exchange. Luminescent measurements were used to verify the number of coordinated waters for Gd-5, and VT (17)O NMR experiments were employed for the highly soluble Gd-TREN-bis-1,2-HOPO-TAM-N3 (Gd-8) complex to measure a fast water exchange rate, (298)k(ex) = 1/tau(M), of 5.1 (+/-0.4) x 10(8) s(-1) ((298)tau(M) approximately 2 ns).
基于1,2 - 羟基吡啶酮螯合剂合成了四种新型钆（III）配合物，并将其作为潜在的磁共振成像造影剂进行了评估。先前关于钆 - TREN - 1,2 - HOPO（3；HOPO = 羟基吡啶酮）的研究表明，1,2 - HOPO单元与钆（III）强烈且选择性地结合，这促使人们对这类化合物的稳定性和弛豫性能进行进一步研究。本文介绍的新型配合物包括同足的钆 - 丝氨酸 - TREN - 1,2 - HOPO（钆 - 5）和三种异足的双 - 1,2 - HOPO - TAM配合物（钆 - 6、钆 - 7和钆 - 8；TAM = 对苯二甲酰胺）。测定了条件稳定常数，所有的pGd值在18.5 - 19.7范围内，与其他类似的HOPO配合物以及目前使用的商业造影剂相当。所有配合物的弛豫率约为商业造影剂的两倍，范围为7.8至10.5 mM⁻¹ s⁻¹（20 MHz；25℃），这表明有两个内球水分子在快速交换。通过发光测量来验证钆 - 5的配位水分子数量，并对高溶解性的钆 - TREN - 双 - 1,2 - HOPO - TAM - N3（钆 - 8）配合物进行变温（17）O NMR实验，以测量快速水交换速率（298）k(ex) = 1/τ(M)为5.1（±0.4）×10⁸ s⁻¹（（298）τ(M)约为2 ns）。
