Raman optical activity of a cyclic dipeptide analyzed by quantum chemical calculations combined with molecular dynamics simulations.

Abstract

Raman optical activity (ROA) measures the different intensity of right- and left-circularly polarized Raman scattered light and provides information on chirality associated with vibrational modes. Because of a high sensitivity to subtle structural and environmental changes, interpretations of ROA spectra usually rely on quantum chemical simulations. Recent advances in computational chemistry allow us to consider explicit solvent models that are derived from molecular dynamics (MD) simulations to compute the Raman and ROA spectra. An important concern for the explicit solvent models is the number of MD snapshots that lead to a good agreement between the observed and calculated spectra. In the present study, we measured the Raman and ROA spectra of cyclo(L-Ala-Gly) and then simulated the spectra using density functional theory combined with MD simulations. Although cyclo(L-Ala-Gly) is a relatively rigid cyclic molecule, boat-up and boat-down conformations were found from the MD calculations. Because the Raman spectra of the two conformations are similar except for a lower frequency region, ∼10 MD snapshots are capable of reproducing the main features of the observed Raman spectra. In contrast, a larger number of MD snapshots was required to reproduce the ROA spectra. In the middle freqency region of 800-1580 cm(-1), an average of ∼40 spectra led to good agreement between the observed and calculated spectra. On the other hand, the low (0-800 cm(-1)) and high (1580-1800 cm(-1)) frequency regions require more than 60 and 120 MD snapshots, respectively. The Raman and ROA spectra in the low frequency region are relatively broad, and such spectral features require a larger number of averaged spectra. The high frequency region of the spectra consists of an amide I band, which is primarily a C═O stretching vibration. Since both the ROA intensity and frequency of the amide I band are highly sensitive to structural and environmental differences, a large number of the spectra need to be averaged to reproduce the small negative features in the observed ROA spectra.