Toward Optimized High-Relaxivity MRI Agents: Thermodynamic Selectivity of Hydroxypyridonate/Catecholate Ligands1

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• 作者：Valé ; rie C. Pierre ; Marco Melchior ; Dan M. J. Doble ; and Kenneth N. Raymond
• 刊名：Inorganic Chemistry
• 出版年：2004
• 出版时间：December 27, 2004
• 年：2004
• 卷：43
• 期：26
• 页码：8520 - 8525
• 全文大小：188K
• 年卷期：v.43,no.26(December 27, 2004)
• ISSN：1520-510X

文摘

The thermodynamic selectivity for Gd³⁺ relative to Ca²⁺, Zn²⁺, and Fe³⁺ of two ligands of potential interest asmagnetic resonance imaging (MRI) contrast agents has been determined by NMR spectroscopy and potentiometricand spectrophotometric titration. The two hexadentate ligands TREN-6-Me-3,2-HOPO (H₃L2) and TREN-bisHOPO-TAM-EA (H₄L3) incorporate 2,3-dihydroxypyridonate and 2,3-dihydroxyterephthalamide moieties. They were chosento span a range of basicity while maintaining a structural motif similar to that of the parent ligand, TREN-1-Me-3,2-HOPO (H₃L1), in order to investigate the effect of the ligand basicity on its selectivity. The 1:1 stability constants(mages/gifchars/beta2.gif" BORDER=0 ALIGN="middle">₁₁₀) at 25 mages/entities/deg.gif">C and 0.1 M KCl are as follows. L2: Gd³⁺, 20.3; Ca²⁺, 7.4; Zn²⁺, 11.9; Fe³⁺, 27.9. L3: Gd³⁺, 24.3;Ca²⁺, 5.2; Zn²⁺, 14.6; Fe³⁺, 35.1. At physiological pH, the selectivity of the ligand for Gd³⁺ over Ca²⁺ increases withthe basicity of the ligand and decreases for Gd³⁺ over Fe³⁺. These trends are consistent with the relative aciditiesof the various metal ions;- more basic ligands favor harder metals with a higher charge-to-radius ratio. Thestabilities of the Zn²⁺ complexes do not correlate with basicity and are thought to be more influenced by geometricfactors. The selectivities of these ligands are superior to those of the octadentate poly(aminocarboxylate) ligandsthat are currently used as MRI contrast agents in diagnostic medicine.