Structural characterization of 2-amino-2-oxoacetic acid by x-ray powder diffraction and quantum chemistry

2-amino-2-oxoacetic acid, carbamoyl formic acid, or oxamic acid is an active pharmaceutical ingredient (API) of great importance mainly because is an inhibitor of lactic dehydrogenase (LDH). It acts as an inhibitor to the metabolic pathways of the tumor cells and exhibited significant anticancer activity against nasopharyngeal carcinoma (NPC) cells in vitro and can be considered as a potential drug for the treatment of type 2 diabetes. Also, this compound could be used as a building block in the design of supramolecular architectures based on hydrogen bonds through the complimentary hydrogen-bond functionalities of the carbonyl and amide functional groups present. Single-crystal X-ray diffraction is the most powerful technique for crystal structure determination of small molecules. However, for several materials, including oxamic acid, it could be complicated to grow single crystals of suitable size and quality that make them appropriated to structure analysis. For this reason, the structural study was conducted with powder X-ray diffraction which is a process significantly more challenging than structure determination from single-crystal data. Oxamic acid has been characterized by FT-IR and NMR spectroscopic techniques, thermal TGA-DSC analysis, semi-empirical PM7 calculations, and X-ray powder diffraction. The title compound crystallizes in the monoclinic system with space group Cc, Z=4, and unit cell parameters a= 9.4994(4) Å, b= 5.4380(2) Å, c= 6.8636(3) Å, β= 107.149(2)°, V= 338.79(2) ų. The molecule has a trans conformation. The molecular structure and crystal packing are stabilized mainly by intra- and inter-molecular O-H·O and N-H·O hydrogen bonds. The structural characterization of this type of API compound is important to understand its mechanisms of action due to its considerable biological effects. In particular, for oxamic acid, this structural study would allow subsequent examination of its medicinal properties as an antitumor and antidiabetic agent.