Prata M I, Santos A C, Geraldes C F, de Lima J J
Serviçio de Biofísica e Biomátematica, Fac. Medicina, Univ. de Coimbra, Portugal.
J Inorg Biochem. 2000 Apr;79(1-4):359-63. doi: 10.1016/s0162-0134(99)00232-9.
The solution chemistry and structure of the complex of the triazamacrocyclic ligand NOTP (1,4,7-triazacyclononane-1,4,7-tris(methylenephosphonate)) with Ga3+ in D2O have been investigated by 1H, 71Ga and 31P NMR spectroscopy. These NMR results show the presence of a 1:1 Ga(NOTP)3- complex, with a highly symmetrical, pseudo-octahedral geometry, possibly with a C3 axis. The 1H spectrum shows that the triazamacrocyclic chelate ring is very rigid, with all the ring protons non-equivalent. The complex is stable in aqueous solution in a wide pH range. Its high thermodynamic stability agrees well with previous results from biodistribution and gamma imaging studies in Wistar rats with 67Ga3+ chelates of triaza macrocyclic ligands, which showed that the neutral chelates 67Ga(NOTA) (where NOTA is 1,4,7-triazacyclononane-1,4,7-triacetate) and 67Ga(NOTPME) (where NOTPME is 1,4,7-triazacyclononane-1,4,7-tris(methylenephosphonate monoethylester)) have similar in vivo behaviour, with high stability and rapid renal excretion, but the high negatively charged 67Ga(NOTP)3- has a considerably slower kidney uptake and elimination.
通过1H、71Ga和31P核磁共振光谱研究了三氮杂大环配体NOTP（1,4,7-三氮杂环壬烷-1,4,7-三（亚甲基膦酸酯））与Ga3+在重水中形成的配合物的溶液化学和结构。这些核磁共振结果表明存在1:1的Ga(NOTP)3-配合物，具有高度对称的伪八面体几何结构，可能具有一个C3轴。1H光谱表明三氮杂大环螯合环非常刚性，所有环质子不等价。该配合物在很宽的pH范围内在水溶液中稳定。其高热力学稳定性与先前在Wistar大鼠中用三氮杂大环配体的67Ga3+螯合物进行的生物分布和γ成像研究结果非常吻合，该研究表明中性螯合物67Ga(NOTA)（其中NOTA是1,4,7-三氮杂环壬烷-1,4,7-三乙酸酯）和67Ga(NOTPME)（其中NOTPME是1,4,7-三氮杂环壬烷-1,4,7-三（亚甲基膦酸单乙酯））具有相似的体内行为，具有高稳定性和快速肾排泄，但高带负电荷的67Ga(NOTP)3-的肾脏摄取和消除相当缓慢。
