The effect of regioisomerism on the coordination chemistry and CEST properties of lanthanide(III) NB-DOTA-tetraamide chelates.
The effect of regioisomerism on the coordination chemistry and CEST properties of lanthanide(III) NB-DOTA-tetraamide chelates.
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DOI：
10.1007/s00775-013-1060-y
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发表时间：
2014-02
影响因子：
3
通讯作者：
Woods, Mark
中科院分区：
文献类型：
--
作者：
Slack, Jacqueline R.;Woods, Mark
关键词：
化学交换饱和转移 (CEST) 作为一种在磁共振图像中生成对比度的方法具有许多优点。然而，目前正在研究的许多外源性试剂都存在检测限，但仍低于更传统的 Gd3+ 试剂所能达到的检测限。为了弥补这一限制，我们对具有异常刚性配体结构的 Ln3+ DOTA-四酰胺螯合物（其中 DOTA 是 1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸）进行了研究：带有（2-苯乙基）酰胺取代基的 DOTA-四酰胺的硝基苄基衍生物。在本报告中，我们研究了掺入疏水性酰胺取代基对水交换和 CEST 的影响。所选择的配体系统总共提供了三种 CEST 活性异构体方形反棱柱形螯合物；发现这些螯合物中的每一种都具有不同的水交换和 CEST 特征。大环上硝基苄基取代基的位置强烈影响螯合物和Ln3+配位笼扭曲的方式。发现这些不同的扭曲会影响螯合物中水质子交换的速率。但是，到目前为止，最大的影响来自于改变疏水性酰胺取代基的位置，当该取代基被迫向上围绕水结合位点时，会导致水质子交换速率的大幅降低。这种缓慢的水质子交换提供了一种螯合物，其作为 CEST 试剂的效率是其在干燥乙腈中的异构体对应物的 4.5 倍，并且在低温和非常低的预饱和功率下。
Chemical exchange saturation transfer (CEST) offers many advantages as a method of generating contrast in magnetic resonance images. However, many of the exogenous agents currently under investigation suffer from detection limits that are still somewhat short of what can be achieved with more traditional Gd3+ agents. To remedy this limitation we have undertaken an investigation of Ln3+ DOTA-tetraamide chelates (where DOTA is 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) that have unusually rigid ligand structures: the nitrobenzyl derivatives of DOTA-tetraamides with (2-phenylethyl)amide substituents. In this report we examine the effect of incorporating hydrophobic amide substituents on water exchange and CEST. The ligand systems chosen afforded a total of three CEST-active isomeric square antiprismatic chelates; each of these chelates was found to have different water exchange and CEST characteristics. The position of a nitrobenzyl substituent on the macrocyclic ring strongly influenced the way in which the chelate and Ln3+ coordination cage distorted. These differential distortions were found to affect the rate of water proton exchange in the chelates. But, by far the greatest effect arose from altering the position of the hydrophobic amide substituent, which, when forced upwards around the water binding site, caused a substantial reduction in the rate of water proton exchange. Such slow water proton exchange afforded a chelate that was 4.5 times more effective as a CEST agent than its isomeric counterparts in dry acetonitrile and at low temperatures and very low presaturation powers.
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影响因子：
2.3
作者：
Baranyai, Zsolt;Banyai, Istvan;Terreno, Enzo
通讯作者：
Terreno, Enzo
影响因子：
3.3
作者：
Sheth, Vipul R.;Li, Yuguo;Chen, Liu Qi;Howison, Christine M.;Flask, Chris A.;Pagel, Mark D.
通讯作者：
Pagel, Mark D.
影响因子：
4.9
作者：
Aime, S;Barge, A;Puschmann, H
通讯作者：
Puschmann, H
影响因子：
3.3
作者：
Ferrauto, Giuseppe;Castelli, Daniela Delli;Aime, Silvio
通讯作者：
Aime, Silvio
影响因子：
4.6
作者：
Miller, Kyle J.;Saherwala, Ali A.;Woods, Mark
通讯作者：
Woods, Mark