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Breaking the Barrier to Slow Water Exchange Rates for Optimal Magnetic Resonance Detection of paraCEST Agents
W Shirangi Fernando1, André F Martins1, Piyu Zhao1
1Department of Chemistry, University of Texas at Dallas , 800 West Campbell Road, Richardson, Texas 75080, United States.
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.
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