A DFT study on the tautomerization of vitamin B3 (niacin)

Abstract

Tautomerization paths of niacin (NA) → its zwitterion (zw) were investigated by DFT calculations. Various models including explicit water molecules [(H2O)n, n = 3, 4, 5, 6, 9 and 14] were examined to simulate the reaction in the aqueous media. Transitions states involving the Grotthuss-type proton-transfer were calculated and their activation free energies were compared to find the likely reaction paths. The route starting from the neutral NA with syn-carboxylic acid was compared with that from NA with anti-COOH. For n = 3 and 3 + 3, the first step is the syn → anti isomerization either via the OH rotation (TS1) or via the proton transfer (TS1′). Here, “n = 3 + 3″ means that three water molecules participate in the proton migration and three ones are peripheral molecules, respectively. The second step is tautomerization through the concerted proton transfer. However, for n = 3 + 6, an ion-pair intermediate Int (n = 3 + 6) was obtained and the n = 3 based route collapsed. On the other hand, for n = 5 + 1, 5 + 4 and 5 + 9, common two-step [NA with syn-COOH → ion pair → NA (zw)] channels were obtained. NA with anti-COOH was suggested to stay only at the [ion pair ⇄ NA with anti-COOH] equilibrium.