Gadolinium(III) complexes of mono- and diethyl esters of monophosphonic acid analogue of DOTA as potential MRI contrast agents:: solution structures and relaxometric studies
Gadolinium(III) complexes of mono- and diethyl esters of monophosphonic acid analogue of DOTA as potential MRI contrast agents:: solution structures and relaxometric studies
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DOI：
10.1039/b612876a
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发表时间：
2007-01-01
影响因子：
4
通讯作者：
Merbach, Andre E.
中科院分区：
文献类型：
--
作者：
Lebduskova, Petra;Hermann, Petr;Merbach, Andre E.
合成了两种新的含有一个膦酸酯侧臂的大环DOTA类螯合物，作为MRI（磁共振成像）的潜在造影剂。螯合物通过四个氮原子、三个羧酸根和一个膦酸根氧原子以八齿方式与镧系元素（III）结合。用P-31和H-1 NMR研究了[Ln（do 3ap（OEt））（H2O）]和[Ln（do 3ap（OEt））（H2O）]（-）的溶液结构，观察到SAP（square-antiprismatic）/TSAP（twisted square-antiprismatic）异构现象。取决于镧系元素（III）离子的性质，H（4）do 3ap（OEt）的镧系元素（III）络合物在溶液中作为用NMR可观察到的多达四种不同的非对映异构体存在。TSAP异构体在镧系元素的开始是最丰富的，并且随着镧系元素（III）离子的离子半径的减小，观察到TSAP和SAP形式。第二次相互转化（SAP TSAP '）在系列结束时变得重要（TSAP'是指没有配位水分子的TSAP物质）。剩余的轴向配位位点被Gd 3 +-络合物的一个水分子占据。钆（III）络合物中TSAP异构体的计算分数以[Gd（DOTA）（H2O）]（-）< [Gd（do 3ap（OEt 2））（H2O）] < [Gd（do 3ap（OEt））（H2O）]（-）< [Gd（do 3ap）（H2O）]（2-）的顺序增加。含磷螯合物的钆（III）络合物通常具有相对快的水交换速率的优点，这是由于磷酸部分的更大空间需求和第二球水壳的存在，这也有助于总弛豫率。[Gd（do 3ap（OEt 2））（H2O）]和[Gd（do 3ap（OEt））（H2O）]（-）配合物用变温O-17 NMR和H-1 NMR进行了研究。实验数据进行了评估，同时与常用的方程的基础上Solomon-Bloembergen-Morgan近似，扩展的贡献的第二配位球。发现水交换速率强烈依赖于TSAP/SAP异构体比率和络合物的总电荷：单阴离子[Gd（do 3ap（OEt））（H2O）]（-）配合物的水交换速率为20 × 10（6）s（-1）（τ（M）= 50 ns），而中性[Gd具有TSAP摩尔分数0.28的（do 3apO（Et 2））（H2O）]络合物的交换速率等于4.4 × 10（6）s（-1）（τ（M）= 227 ns）。
Two new macrocyclic DOTA-like chelates containing one phosphonate pendant arm were synthesised as potential contrast agents for MRI ( magnetic resonance imaging). The chelates bind to the lanthanide(III) in an octadentate manner, via four nitrogen atoms, three carboxylate and one phosphonate oxygen atoms. Solution structures of [Ln(do3apO(Et2))(H2O)] and [Ln(do3ap(OEt))(H2O)](-) were studied using P-31 and H-1 NMR spectroscopy and SAP (square-antiprismatic)/TSAP ( twisted square-antiprismatic) isomerism was observed. Depending on the nature of the lanthanide( III) ion, the lanthanide( III) complexes of H(4)do3ap(OEt) are present in solution as up to four different diastereoisomers observable with NMR. The TSAP isomer is the most abundant at the beginning of the lanthanide series and, with a decrease of the ionic radius of lanthanide( III) ions, both TSAP and SAP forms were observed. A second interconversion (SAP TSAP') becomes important at the end of the series (TSAP' means the TSAP species without a coordinated water molecule). The remaining axial coordination site is occupied by one water molecule for the Gd3+-complex. The calculated fraction of the TSAP isomer in the gadolinium( III) complexes increases in the order [Gd(DOTA)(H2O)](-) < [Gd(do3ap(OEt2))(H2O)] < [Gd(do3ap(OEt))(H2O)](-) < [Gd(do3ap)(H2O)](2-). Gadolinium( III) complexes of phosphorus-containing chelates, generally, have the advantage of a relatively fast water exchange rate due to a greater sterical demand of the phosphorus acid moiety and of the presence of the second-sphere water shell, which also contributes to the overall relaxivity. The [Gd(do3ap(OEt2))(H2O)] and [Gd(do3ap(OEt))( H2O)](-) complexes were studied by variable-temperature O-17 NMR and H-1 NMRD. The experimental data were evaluated simultaneously with commonly used equations based on Solomon-Bloembergen-Morgan approximation, extended by a contribution of the second coordination sphere. The water exchange rates were found to be strongly dependent on the TSAP/SAP isomeric ratio and the overall charge of the complex: the monoanionic [Gd(do3ap(OEt))(H2O)](-) complex with TSAP molar fraction equal to 0.36 has the water exchange rate of 20 x 10(6) s(-1) (tau(M) = 50 ns) while neutral [Gd(do3apO(Et2))(H2O)] complex with TSAP molar fraction 0.28 has an exchange rate equal to 4.4 x 10(6) s(-1) (tau(M) = 227 ns).