Theoretical study on the relative energies of cationic pterin tautomers

Abstract Pterins are heterocyclic molecules of biological importance that contain several basic sites. These molecules can be protonated in aqueous solution resulting in a wide variety of structures that differ in their site of protonation and tautomeric form. In the present study, density functional theory (DFT) calculations were used to determine the relative energies of various protonated tautomers of 6-methylpterin in aqueous solution. A total of 32 different structures are compared resulting from protonation at six different sites on six pterin tautomers. MP2 calculations were also used to support the calculated energies of the six most stable structures. We find that the most basic sites among all 6-methylpterin tautomers is N1, N8, and N5 of the lactam, respectively, followed by N1 of the lactim. Calculated charge densities of the neutral 6-methylpterin structures using a natural population analysis (NPA) support protonation at these sites.