Protonation Sequence Study of the Solution Structure of DTPA by 1H NMR

The protonation sequence of DTPA is evaluated using a 300 MHz H NMR instrument. A terminal nitrogen is protonated first (pK_a1,2=10.02, 8.45). Upon the first protonation a dynamic hydrogen bonded five membered ring is formed between the terminal nitrogen and the central nitrogen. The second equivalent of protons protonates the opposite terminal amine and causes the ring to open. The third protonation (pK_a3=4.65) takes place on the central acetate and forms a ring with the central amine. The fourth protonation is assigned to a terminal acetate. The formation of five membered rings involving hydrogen bonding gives a better quantitative and qualitative account for the unusual shifts observed in the H NMR spectra than previous explanations.