Synthesis, Protonation Sequence, and NMR Studies of Polyazamacrocyclic Methylenephosphonates

Macroscopic and microscopic protonation of a series of cyclic polyamino polyphosphonic acids (NOTP, DOTRP, and DOTP) was studied by using potentiometry and multinuclear magnetic resonance spectroscopy. The macroscopic protonation constants of these ligands were compared with those of the cyclic amines and corresponding acetate derivatives. Chemical shifts for the various protonated species derived from the³¹P and¹H resonances are interpreted in terms of preferred conformational features due to intramolecular hydrogen bonding between protonated nitrogens and nonprotonated phosphonates and changes in phosphonate electronic structures with pH. Protonation sequences were obtained from the proton data by using published procedures. The data suggest that two nitrogens are protonated first in each compound followed by protonation of the phosphonate oxygens. In the triaza ligands, the third and fourth protonations occur at the phosphonate oxygens, and subsequent protons distribute between the remaining nitrogen and oxygens. This protonation scheme is quite similar to that previously observed for the analogous macrocycles containing acetate pendant groups.