Crystal structures of two polymorphic forms of DOTAM-mono-acid dihydrate

The structural chemistry of 2-[4,7,10-tris(carbamoylmethyl)-1,4,7,10-tetraazacyclododecan-1-yl]acetic acid dihydrate, C₁₆H₃₁N₇O₅·2H₂O, is described. The macrocyclic compound, also known by the abbreviation DOTAM-mono-acid, crystallized at room temperature and was isolated concomitantly as two polymorphic forms. The structures of both polymorphs were determined at 90 K. The first polymorph crystallized as a zwitterionic dihydrate [systematic name: 4,7,10-tris(carbamoylmethyl)-1-(carboxylatomethyl)-1,4,7,10-tetraazacyclododecan-1-ium dihydrate] in the space group P2₁/n, with Z' = 1. The second polymorph crystallized as a zwitterionic dihydrate in the space group P2₁ at 90 K, with Z' = 2. The two independent molecules are related by a local center. In each polymorph, the zwitterion is formed between the negatively-charged carboxylate group and the ring N atom that bears the acetate pendant arm. Extensive inter- and intramolecular hydrogen bonding exists in both polymorphic structures. In polymorph 1, an intermolecular hydrogen-bonding network propagating parallel to the a direction creates an infinite chain. A second hydrogen-bonding network is observed through a water molecule of hydration in the b direction. Polymorph 2 also has two intermolecular hydrogen-bonding networks. One propagates parallel to the a direction, while the other propagates in the [-110] direction. Increasing the temperature of polymorph 2 yields the same structure at T = 180 K, but the pseudocenter becomes exact at 299 K. The higher-temperature structure has Z' = 1 in the space group P2₁/c.