title: Vibrational analysis of amino acids and short peptides in hydrated media. VII. Energy landscapes, energetic and geometrical features of L-histidine with protonated and neutral side chains.
abstract: In manuscript VI of the same series (J. Phys. Chem. B 2010, 114, 1077-1088), we reported the geometrical and vibrational features of lysine and arginine, that is, two alpha-amino acids (alpha-AAs) with positively charged side chains, at physiological conditions. Here, we report our results on histidine, one of the most biologically important alpha-AAs, whose side chain can be neutral or positively charged through a protonation-deprotonation process of the nitrogens involved in its cyclic side chain at pH values in the physiological range. We have recorded at room temperature Raman scattering and Fourier-transform infrared (FT-IR) absorption spectra from the aqueous solutions of the AA at pH values 4, 6.8, and 8. It has been shown that a Raman spectrum recorded at the intermediate pH (6.8) can be perfectly reconstituted by a linear combination of those observed at two extreme pH values (4 and 8), allowing determination of the populations of histidine with protonated and neutral side chains in solution. The above-mentioned experimental data were completed by the vibrational spectra recorded in D(2)O. On the other hand, quantum mechanical calculations at the DFT/B3LYP/6-31++G* allowed us to analyze the energetic, geometrical, and vibrational features of histidine. Through a discussion on the basis of experimental and theoretical results, we comment on (i) the potential energy surfaces of histidine placed in a polarizable dielectric continuum, providing molecular energy landscapes as a function of its side chain orientations around C(alpha)-C(beta) and C(beta)-C(gamma) bonds; (ii) the full geometry optimization of the low energy conformers placed in a solvent continuum or in the presence of n explicit water molecules (n = 3, 7); (iii) the energy value separating the two histidine forms with neutral side chains; (iv) the determination of the side chain pK(a) by means of Raman spectra; and (v) the assignment of the observed vibrational modes by means of the lowest-energy conformers of hydrated histidine.
authors.affiliation: Groupe de Biophysique Moléculaire, UFR Santé-Médecine-Biologie Humaine, Université Paris 13, 74 rue Marcel Cachin, 93017 Bobigny cedex, France.
authors.forename: Fernando
authors.initials: F
authors.lastname: Pflüger
authors.forename: Belén
authors.initials: B
authors.lastname: Hernández
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Ghomi
mesh_terms: D006639:Histidine / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry*; D011522:Protons; D011789:Quantum Theory; D012997:Solvents / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D013816:Thermodynamics; D014732:Vibration; D014867:Water / Q000737:chemistry
chemical_list: D010455:Peptides; D011522:Protons; D012997:Solvents; D014867:Water; D006639:Histidine