Vibrational Spectra, Conformations, and Optical Rotation of Aqueous Amino Acids: Zwitterions of L-Alanine and...

We demonstrate that an efficient computational protocol for accurate quantum mechanical (QM) modeling of IR and Raman spectra of condensed-phase systems is applicable to aqueous zwitterions of L-alanine and L-valine. The approach is based on generating energetically low-lying cluster structures consisting of the solute surrounded by an explicit solvation shell, optimized at the DFT level. Such cluster models are shown to reliably reproduce experimental vibrational frequencies and relative IR and Raman intensities of both amino acids at the B3LYP-D3/def2-TZVP level, provided that 25 water molecules are included. The accuracy of the simulations is sufficient to resolve all three conformers of valine and to identify their spectroscopic signatures. Relative conformer populations are estimated from the experimental intensities of the corresponding conformational marker bands, and conformationally averaged optical rotations (OR) of valine are computed using several QM protocols for [α]_D. A comparative analysis of the full set of computed OR values for both amino acids yields an intrinsic margin of error in TDDFT calculations of [α]_D of approximately 50° cm³/(g dm).