Quantum-chemical studies of amide-iminol tautomerism for inhibitor of lactate dehydrogenase: Oxamic acid

Amide-iminol tautomerism was studied for oxamic acid (OA) in the gas phase using various quantum-chemical methods (HF, MP2, DFT, and G2). All possible twenty tautomers-rotamers, four amide and sixteen iminol forms, were considered for the neutral molecule. At each level of theory, the amidization process (amide ← iminol) is favored for OA similarly as for the parent compound (formamide). Three amide and fourteen iminol rotamers of OA are found to be thermodynamically stable, among which the intramolecularly H-bonded amide structure has the lowest Gibbs free energy (G) in the gas phase. Low relative energies for the two other amide structures indicate that all of them may be present in the tautomeric mixture of OA. The G value of the most stable iminol structure is larger than those of the three amide isomers by ca. 10 kcal mol−1. This suggests that the amide form(s) of OA may be responsible for binding with large biomolecules (proteins, enzymes, receptors) and particularly for bioseparation of lactate dehydrogenase (LDH).