Semiempirical SCF-MO calculations on the tautomeric equilibrium of histamine in gas phase and in aqueous solution

Abstract

The potential energy surface of hstamine monocation is calculated by MNDO types methodologies and by the Reaction Field model at CNDO/2 level, in order to rationalize the experimental findings about the relative abundance of histamine monocation tautomers in gas phase and in aqueous solution, respectively. The results indicate that the most stable form in gas phase exhibits an intramolecular H-bonding between the imidazolic and the amino N atoms. The corresponding proton transfer potential energy function across the H-bridge calculated in vacuum, consists of an asymmetric double well curve favoring the form which the proton is mainly bonded to the aromatic N atom. The influence of the solvent polarity on the H-bridge structure consists on an inversion of the minima in the proton transfer curve, together with a lowering of the torsional energy barrier of the side chain respect to the aromatic ring. Finally, a mechanism involving an intramolecular proton transfer, which explains the tautomeric equilibrium of histamine from gas phase to aqueous solution is proposed. The mechanism is rationalized in terms of charges distribution and HOMOs characterization.