Equilibrium and NMR Relaxometric Studies on the s-Triazine-Based Heptadentate Ligand PTDITA Showing High Selectivity for Gd3+ Ions

详细信息    查看全文

• 作者：Zsolt Baranyai ; Lorenzo Tei ; Giovanni B. Giovenzana ; Ferenc K. K谩lm谩n ; Mauro Botta
• 刊名：Inorganic Chemistry
• 出版年：2012
• 出版时间：February 20, 2012
• 年：2012
• 卷：51
• 期：4
• 页码：2597-2607
• 全文大小：483K
• 年卷期：v.51,no.4(February 20, 2012)
• ISSN：1520-510X

文摘

A complete potentiometric and NMR relaxometric solution study on the heptadentate 2,2鈥?2鈥?2鈥测€?[(6-piperidinyl-1,3,5-triazine-2,4-diyl)dihydrazin-2-yl-1-ylidene]tetraacetic acid (PTDITA) ligand has been carried out. This ligand is based on the 1,3,5-triazine ring with two hydrazine-N,N-diacetate groups in positions 2 and 4 and a piperidine moiety in position 6. The introduction of the triazine ring into the ligand backbone is expected to modify its flexibility and then to affect the stability of the corresponding complexes with transition-metal and lanthanide ions. Thermodynamic stabilities have been determined by pH potentiometry, UV spectrophotometry, and ¹H NMR spectroscopy for formation of the complexes with Mg²⁺, Ca²⁺, Cu²⁺, Zn²⁺, La³⁺, Gd³⁺, and Lu³⁺ ions. PTDITA shows a good binding affinity for Gd³⁺ (logK = 18.49, pGd = 18.6) and an optimal selectivity for Gd³⁺ over the endogenous Ca²⁺, Zn²⁺, and Cu²⁺ (K_sel = 6.78 脳 10⁷), which is 3 orders of magnitude higher that that reported for Gd(DTPA) (K_sel = 2.85 脳 10⁴). This is mainly due to the lower stability of the Cu^II- and Zn^II(PTDITA) complexes compared to the corresponding DTPA complexes, which suggests an important role of the triazine ring on the selectivity for the Gd³⁺ ion. The relaxometric properties of Gd(PTDITA) have been investigated in aqueous solution by measuring the ¹H relaxivity as a function of the pH, temperature, and magnetic field strength (nuclear magnetic relaxation dispersion profile). Variable-temperature ¹⁷O NMR data have provided direct information on the kinetic parameters for exchange of the coordinated water molecules. A simultaneous fit of the data suggests that the high relaxivity value (r₁ = 10.2 mM^鈥? s^鈥?) is a result of the presence of two inner-sphere water molecules along with the occurrence of relatively slow rotation and electronic relaxation. The water residence lifetime, ²⁹⁸蟿_M = 299 ns, is quite comparable to that of clinically approved magnetic resonance imaging contrast agents. The displacement of the inner-sphere water molecules by bidentate endogeneous anions (citrate, phosphate, and carbonate) has also been evaluated by ¹H relaxometry. In general, the binding interaction is markedly weak, and only in the case of citrate, a ca. 35% decrease in relaxivity was observed in the presence of 60 equiv of the anion. Phosphate and carbonate also interact with the paramagnetic ion, likely as monodentate ligands, but formation of the ternary complex is accompanied by a modest increase of r₁ due to the contribution of second-sphere water molecules.