The ligand, 1,4,7,10-tetraazacyclododecane-1,4,7,10- tetrakis(methylenephosphonic acid, ethyl ester) (DOTPME) was made membrane permeable by preparing its acetoxymethyl (AM) derivative (DOTPME-AM). The synthetic approach was to prepare the AM ester of the phosphonate side-chain prior to attachment to the macrocyclic ring. P NMR was used to demonstrate that DOTPME-AM can penetrate cell membranes, get hydrolyzed by cellular esterases to regenerate charged DOTPME, and hence become trapped inside cells. This technology offers the potential of designing Ca2+ and Mg2+ specific ligands for analytical, noninvasive measurement of these ions by 31P NMR.
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