Impact of rigidification on relaxometric properties of a tricyclic tetraazatriacetic gadolinium chelate
Impact of rigidification on relaxometric properties of a tricyclic tetraazatriacetic gadolinium chelate
复制标题
DOI：
10.1002/cmmi.99
复制
发表时间：
2006-05-01
影响因子：
--
通讯作者：
Guy, Alain
中科院分区：
文献类型：
--
作者：
Port, Marc;Raynal, Isabelle;Guy, Alain
合成了Gd-PCTA12的约束衍生物gd -环pcta12，其中一个连接三胺块的两个氮原子的乙烯桥被一个环己烯桥取代，并通过比较Gd-PCTA12和gd -环pcta12两种钆MRI造影剂的物理化学和弛豫性能，研究了刚性的影响。该配合物在20 MHz和310 K下的质子弛豫度r(1) =6.1 s(-1) mM(-1)，比母体化合物具有更高的质子弛豫度。PCTA12支架的固化对内源离子（如Zn2+）对金属转化的惰性没有影响。此外，这两种造影剂的弛豫都没有被内源性阴离子猝灭。氧-17 NMR研究和NMRD谱表明，PCTA支架的刚性对gd -环-PCTA 12的电子弛豫没有影响。然而，由于钆离子周围的空间拥挤，这种配合物的刚性引起了球内水分子交换速率的加速。因此，当螯合剂通过共价或非共价与大分子结合而固定时，tau(310)(M)的值接近获得高弛豫所需的最佳值。版权所有(C) 2006 John Wiley & Sons, Ltd。
A constrained derivative of Gd-PCTA12, Gd-cyclo-PCTA12, in which one ethylene bridge connecting two nitrogen atoms of the triamine block is replaced by a cyclohexylene bridge, was synthesized and the impact of rigidification was studied by comparing the physicochemical and relaxometric properties of both gadolinium MRI contrast agents, Gd-PCTA12 and Gd-cyclo-PCTA12. The new complex has higher proton relaxivity than the parent compound (r(1) =6.1 s(-1) mM(-1) at 20 MHz and 310 K). The rigidification of the PCTA12 scaffold proved to have no impact on the inertness towards transmetallation by endogenous ions such as Zn2+. Moreover, for both contrast agents, the relaxivity was not quenched by endogenous anions. The oxygen-17 NMR study and the NMRD profile demonstrated that the rigidification of the PCTA scaffold had no impact on the electronic relaxation of Gd-cyclo-PCTA 12. However, the rigidity of this complex induced an acceleration of the exchange rate of the inner-sphere water molecules as a result of steric crowding around the gadolinium ion. The value of tau(310)(M) thus approached the optimal value required to attain high relaxivity once the chelate is immobilized by covalent or non-covalent binding to macromolecules. Copyright (C) 2006 John Wiley & Sons, Ltd.