Synthesis, Potentiometry, and NMR Studies of Two New 1,7-Disubstituted Tetraazacyclododecanes and Their Complexes Formed with Lanthanide, Alkaline Earth Metal, Mn²⁺, and Zn²⁺ Ions^⊥

Two new 1,7-disubstituted-1,4,7,10-tetraazacyclododecane ligands, DO2P and DO2PME, and their complexes with Mg²⁺, Ca²⁺, Sr²⁺, Mn²⁺, Zn²⁺ and Ln³⁺ were prepared and characterized by pH potentiometry. The pH titration data showed that DO2P and DO2PME both form 1:1 M:L complexes with all divalent and trivalent metal ions. Protonated complexes did not appear to form with the bis(phosphonate ester) ligand, DO2PME, but were evident for all of the metal ion-DO2P complexes. The alkaline earth metal ion-DO2P complexes formed both ML and MHL complexes while the lanthanide ion (Ln³⁺), Zn²⁺, and Mn²⁺ complexes of DO2P formed ML, MHL, and MH₂L species. Zn²⁺ formed the most stable complex with both ligands. The stability (β₁₀₁) of the LnDO2PME⁺ complexes increased by about 2 orders of magnitude along the lanthanide series (La³⁺ to Lu³⁺) while the stability of the LnDO2P^- complexes over this same series increased by over 3 orders of magnitude. The bis(phosphonate) ligand, DO2P, and some of its complexes formed with Ln³⁺ ions were further examined by NMR spectroscopy. ¹H and ³¹P spectra of DO2P collected as a function of pH provided evidence that the first two protonations on the ligand take place largely at the tertiary nitrogens. The similarity of the ³¹P chemical shifts of EuDO2P^- and EuDOTP^5- indicate that DO2P forms an "in-cage" complex with Eu³⁺ using all four macrocyclic ring nitrogens and the two phosphonate sidearms as ligands. ¹⁷O NMR shifts of the water signal indicated that the DyDO2P^- complex has two inner-sphere coordinated water molecules. In the presence of excess of DO2P, a 1:2 metal:ligand, LnDO2P(HDO2P)^4-, complex forms with the second ligand interacting only weakly with the coordination sites left vacant by the first DO2P. Both water proton relaxivity data for GdDO2P^- and ³¹P NMR spectra of EuDO2P^- provide evidence for formation of an "out-of-cage" LnH₂DO2P⁺ complex at low pH values (<6.5) in which the two phosphonate groups of DO2P are only involved in bonding with the lanthanide cation.