HCN, Formamidic Acid, and Formamide in Aqueous Solution: A Free-Energy Map

What chemical species might be found if water or ammonia reacts with HCN in aqueous solution under neutral conditions? Is it energetically favorable for formamidic acid, the first hydration product of HCN, to tautomerize into formamide under standard conditions? Do these molecules form stable oligomers in solution? To answer these questions, we constructed a Gibbs free-energy map of the molecules that might be present to evaluate their relative thermodynamic and kinetic stability. Our protocol utilizes density functional theory calculations, Poisson-Boltzmann implicit solvent, and thermodynamic corrections. We find that for C1 species, formamide is indeed the thermodynamic sink, although the initial barrier to hydration is ∼30 kcal/mol. Molecules with one carbon and three heteroatoms are less stable. We also find that for HCN trimerization, although the planar sp(2) six-membered ring is more stable compared to its monomers, the reverse is true for the nonplanar sp(3) six-membered rings formed by trimerization of formamidic acid or formamide.