突破阻碍以减缓水交换速率，实现对顺磁化学交换饱和转移（paraCEST）试剂的最佳磁共振检测。

Breaking the Barrier to Slow Water Exchange Rates for Optimal Magnetic Resonance Detection of paraCEST Agents.

作者信息

Fernando W Shirangi, Martins André F, Zhao Piyu, Wu Yunkou, Kiefer Garry E, Platas-Iglesias Carlos, Sherry A Dean

机构信息

Department of Chemistry, University of Texas at Dallas , 800 West Campbell Road, Richardson, Texas 75080, United States.

Advanced Imaging Research Center, University of Texas Southwestern Medical Center , Dallas, Texas 75390, United States.

出版信息

Inorg Chem. 2016 Mar 21;55(6):3007-14. doi: 10.1021/acs.inorgchem.5b02850. Epub 2016 Mar 3.

DOI:10.1021/acs.inorgchem.5b02850

PMID:26937683

Abstract

EuDOTA-tetraamide complexes as paraCEST agents offer an attractive platform for designing biological sensors and responsive agents. The early versions of these agents showed low sensitivity at temperature and power levels suitable for in vivo applications partly due to non-optimal water exchange rates. Here we report two new EuDOTA derivatives having glutamyl-phosphonate side arms that display the slowest water exchange rates of any other paraCEST agent reported so far. The advantages of such systems are demonstrated experimentally both in vitro and in vivo and DFT calculations were performed to help understand the physical-chemical reasons for this interesting behavior.

摘要

作为顺磁化学交换饱和转移（paraCEST）剂的铕双三齿四酰胺配合物为设计生物传感器和响应剂提供了一个有吸引力的平台。这些试剂的早期版本在适合体内应用的温度和功率水平下表现出低灵敏度，部分原因是水交换速率不理想。在此，我们报道了两种具有谷氨酰膦酸酯侧链的新型铕双三齿四酰胺衍生物，它们展现出迄今为止报道的任何其他paraCEST试剂中最慢的水交换速率。这种体系的优势在体外和体内实验中均得到了证明，并且进行了密度泛函理论（DFT）计算以帮助理解这种有趣行为的物理化学原因。