A Synthetic Route to Cell Permeable, Macrocyclic-Based Phosphonate Acyloxymethyl Esters

Four cell membrane-permeant derivatives of polyaza macrocyclic ligands, including acetoxymethyl (AM) and pivaloyloxymethyl (POM) esters of 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetrakis(ethyl methylenephosphonate) (DOTPME) and 1,4,7-triazacyclononane- 1,4,7-tris(ethyl methylenephosphonate) (NOTPME), were prepared as model systems for the detection of intracellular ions by 31P NMR spectroscopy. Preliminary results on isolated perfused rat hearts suggest that such ligands may be useful for monitoring intracellular levels of Ca2+ and Mg2+.