CHARACTERIZATION OF LANTHANIDE COMPLEXES WITH A SERIES OF AMIDE-BASED MACROCYCLES, POTENTIAL MRI CONTRAST AGENTS, USING EU3+ LUMINESCENCE SPECTROSCOPY AND MOLECULAR MECHANICS

Eu3+ luminescence spectroscopy was used to characterize the solution complexes of the following ligands: 4,10,-13-tris(carboxymethyl)-8,15-dioxo-1,4,7,10,13-pentaazacyclopentadecane (edta-dam); 1,4,7-tris(carobxymethyl)-9,14-dioxo-1,4,7,10,13-pentaazacyclopentadecane (edta-dam); 1,4,7-tris(carboxymethyl)-9,14-dioxo-1,4,7,10,13-pentaazacyclopentadecane (dtpa-eam); 1,4,7-tris(carboxymethyl)-9,20-dioxo-13,16-dioxa-1,4,7,10,19-pentaazacycloheneicosane (dtpa-oam); 1,4,7,16,19,22-hexa(carboxymethyl)-9,14,24,29-dioxo-1,4,7,10,13,16,19,22,25,28-decaazacyclotriacontane (bis(dtpa-eam)), 1,4-bis((4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl)acetyl)piperazine (piperazine do3a-dimer). A single isomeric form of the Eu3+ complex with each ligand is observed. Edta-dam, dtpa-eam, and dtpa-oam form 1:1 stoichiometric metal-ligand complexes while bis(dtpa-eam) and the do3a-dimer form 2:1 stoichiometric metal-ligand complexes. Formation constants were measured for the Eu3+ complexes of dtpa-eam, dtpa-oam, and edta-dam. Relative formation constants for the other members of the lanthanide series were measured by competition experiments for dtpa-eam, dtpa-oam, and edta-dam. The number of coordinated water molecules were determined for the Eu3+ complex of each ligand. Inter-metal ion energy transfer between the Eu3+ ion and various other coordinated lanthanide ions is observed in dinuclear complexes of bis(dtpa-eam) and the piperazine do3a-dimer. Deductions regarding the composition of the first coordination sphere of the Eu3+ ion were made on the basis of molecular mechanics calculations and the number of coordinated water molecules determined from excited-state lifetime measurements in H2O and D2O.