A benzene-core trinuclear GdIII complex:: towards the optimization of relaxivity for MRI contrast agent applications at high magnetic field
A benzene-core trinuclear GdIII complex:: towards the optimization of relaxivity for MRI contrast agent applications at high magnetic field
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DOI：
10.1039/b717390c
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发表时间：
2008-01-01
影响因子：
4
通讯作者：
Toth, Eva
中科院分区：
文献类型：
--
作者：
Livramento, Joao Bruno;Helm, Lothar;Toth, Eva
合成了一种以三甲基苯为核，含三个亚甲基二乙烯三胺-N，N，N“，N”-四乙酸酯（-CH（2）DTTA（4-））的新型配体H12 L，并研究了其三核Gd 3+配合物[Gd 3L（H2O）（6）]（3-）在MRI造影剂中的应用.多场变温O-17 NMR和质子弛豫研究[Gd 3L（H2O）（6）]（3-）得到表征水交换和旋转动力学的参数。根据O-17化学位移，可以证明Gd 3+的双氢化。水交换速率，k（ex）（298）= 9.0 +/- 3.0 s（-1）是商业[Gd（DTPA）（H2O）]（2-）的k（ex）（298）的大约两倍高，并且与类似的Gd 3 +-DTTA螯合物相当。尽管复杂的规模相对较小，旋转动力学必须用Lipari-Szabo方法描述，通过分离全局和局部运动。局部和全局旋转相关时间之间的差异分别为tau（298）（IO）= 170 +/- 10 ps和tau（298）（gO）= 540 +/- 100 ps，表明[Gd 3L（H2O）（6）]（3）-不是完全刚性的;其柔性源于苯核和聚（氨基羧酸酯）部分之间的CH 2连接基。由于每个Gd 3+有两个内球水分子，它们接近最佳的交换速率和适当的大小以及分子的有限柔性，当与商业造影剂相比时，[Gd 3L（H2O）（6）]（3）-具有显著的质子弛豫性，特别是在高磁场下（r（1）= 21.6、17.0和10.7 mM（-1）s（-1），60，分别为200和400 MHz，25 ℃; r1是纵向水质子弛豫速率的顺磁增强，涉及1 mM浓度的Gd 3+）。
A novel ligand, H12L, based on a trimethylbenzene core bearing three methylenediethylenetriamine-N, N, N '', N ''- tetraacetate moieties (-CH(2)DTTA(4-)) for Gd3+ chelation has been synthesized, and its trinuclear Gd3+ complex [Gd3L(H2O)(6)](3-) investigated with respect to MRI contrast agent applications. A multiple-field, variable-temperature O-17 NMR and proton relaxivity study on [Gd3L(H2O)(6)](3-) yielded the parameters characterizing water exchange and rotational dynamics. On the basis of the O-17 chemical shifts, bishydration of Gd3+ could be evidenced. The water exchange rate, k(ex)(298)= 9.0 +/- 3.0 s(-1) is around twice as high as k(ex)(298) of the commercial [Gd(DTPA)(H2O)](2-) and comparable to those on analogous Gd3+-DTTA chelates. Despite the relatively small size of the complex, the rotational dynamics had to be described with the Lipari-Szabo approach, by separating global and local motions. The difference between the local and global rotational correlation times, tau(298)(IO) = 170 +/- 10 ps and tau(298)(gO) = 540 +/- 100 ps respectively, shows that [Gd3L(H2O)(6)](3)-is not fully rigid; its flexibility originates from the CH2 linker between the benzene core and the poly(amino carboxylate) moiety. As a consequence of the two inner-sphere water molecules per Gd3+, their close to optimal exchange rate and the appropriate size and limited flexibility of the molecule, [Gd3L(H2O)(6)](3)-has remarkable proton relaxivities when compared with commercial contrast agents, particularly at high magnetic fields (r(1) = 21.6, 17.0 and 10.7 mM(-1)s(-1) at 60, 200 and 400 MHz respectively, at 25 degrees C; r1 is the paramagnetic enhancement of the longitudinal water proton relaxation rate, referred to 1 mM concentration of Gd3+).