Many paraCEST agents have reduced sensitivity in vivo due to the reduction of the T2 relaxation of bulk water by T2ex exchange. Phosphonate coordinating side-chains in cyclen-based complexes exclude inner sphere water and this should reduce the interfering T2ex effects. In the new complexes reported here, a combination of phosphonate and hydroxypropyl pendant arms were incorporated to take advantage of the CEST signal from the Ln-bound OH. Protonation of the coordinating phosphonates results in a shift in the resonance frequency of Ln-bound OH CEST. These agents display several attractive features for imaging tissue pH in vivo by CEST MRI.
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