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

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.