title: Structural and vibrational study of the tautomerism of histamine free-base in solution.
abstract: Infrared and Raman spectroscopy in H(2)O and D(2)O and quantum Density Functional calculations were used to determine the structure of histamine free-base in aqueous solution. A quantum mechanical study of the tautomeric equilibrium of histamine free-base in solution was performed at the 6-311G level. Electronic correlation energies were included by using the hybrid functional B3LYP. The solvent was simulated as a continuum characterized by a dielectric constant, and the quantum system (solute) was placed in an ellipsoidal cavity. Solute-solvent electrostatic interaction was calculated by means a multipolar moment expansion introduced in the Hamiltonian. Four relevant histamine conformations were optimized by allowing all the geometrical parameters to vary independently, which involved both the gauche-trans and the N3H-N1H tautomerisms. The calculated free energies predicted N3H-gauche as the most stable one of histamine free-base in solution. The order of stability is here completely altered with respect to previous results in gas phase, which presented the N1H-gauche conformer as the most stable structure. Our results also differ from previous Monte Carlo simulations, which obtained the N3H-trans conformer as the most stable in solution, although in this case, the histamine structures were kept frozen to the gas-phase geometry. Vibrational spectroscopy results support theoretical ones. Quadratic force fields for the four histamine conformers were achieved under the same calculation methodology. Previously, a general assignment of the infrared and Raman spectra of histamine free-base was proposed for solutions in both natural and heavy water. This allowed us to compare the experimental set of both wavenumbers and infrared intensities with the calculated ones. The lowest quadratic mean wavenumber deviation was obtained for the N3H-gauche conformer, in agreement with the free-energy calculations. Calculated infrared intensities were also compared to the experimental intensities, supporting this conformer as the relevant structure of histamine free-base in solution. It was then selected for a complete vibrational dynamics calculation, starting with a low-level scaling procedure to fit the set of calculated wavenumbers to the experimental values. The results were presented in terms of quadratic force constants, potential energy distribution, and normal modes.
authors.affiliation: Departamento de Química Física, Facultad de Ciencias, Universidad de Málaga, Campus de Teatinos, 29071-Málaga, Spain. ramirez@uma.es
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Ramírez
authors.forename: Iñaki
authors.initials: I
authors.lastname: Tuñón
authors.forename: Juan A
authors.initials: JA
authors.lastname: Collado
authors.forename: Estanislao
authors.initials: E
authors.lastname: Silla
mesh_terms: D006632:Histamine / Q000737:chemistry*; D015394:Molecular Structure; D011789:Quantum Theory; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D013816:Thermodynamics
chemical_list: D012996:Solutions; D006632:Histamine