fac -99m Tc/Re-tricarbonyl complexes with tridentate aminocarboxyphosphonate ligands: suitability of the phosphonate group in chelate ligand design of new imaging agents

Inorganica Chimica Acta
Malgorzata LipowskaLuigi G Marzilli

Abstract

Ligands that coordinate via dianionic phosphonate groups have not been widely utilized in radiopharmaceuticals. N-(phosphonomethyl)iminodiacetic acid (1, PMIDA) and N-(phosphonomethyl)glycine (2, PMG) were investigated as new chelators for the 99mTc/Re-tricarbonyl "core" (fac-M(CO)3, M = 99mTc, Re) present in a major class of radiopharmaceuticals. fac-M(CO)3(PMIDA) and fac-M(CO)3(PMG) complexes were studied by HPLC and 1H/13C/31P NMR methods for M = Re (Re-1 and Re-2) and by HPLC for M = 99mTc ( 99m Tc-1 and 99m Tc-2). Re-1 and 99mTc-1 complexes exhibit a similar pH-dependent equilibrium between geometric linkage isomers (M-1a and M-1b). However, only one isomer exists for M-2 under all conditions. Structural characterization by X-ray crystallography reveals the presence of a bond between a phosphonate oxygen and the Re(I) center in fac-Re(CO)3(PMG) (Re-2). Detailed comparisons of NMR data for Re-2 conclusively demonstrate that the phosphonate group is coordinated in Re-1b (isomer favored at high pH) but not in Re-1a, which has a dangling N-(phosphonomethyl) group. To our knowledge, Re-1b and Re-2 and their 99mTc analogs are the first well-documented examples of complexes with these metal-tricarbonyl cores having a dianionic ...Continue Reading

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Citations

Feb 23, 2021·Asian Journal of Pharmaceutical Sciences·Panoraia I SiafakaEvren Atlıhan Gündoğdu

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