Interpretation of Raman and Raman Optical Activity Spectra of a Flexible Sugar Derivative, the Gluconic Acid Anion

Abstract

Raman scattering and its polarized extension, Raman optical activity (ROA), are commonly used for monitoring of molecular conformational equilibria in solutions. This is complicated for saccharides due to extensive motions of the hydroxyl groups and other molecular parts. Standard interpretation procedures involving ab initio spectral simulations for a limited set of conformers are not adequate. In this study, a more general approach is proposed for the gluconic acid anion taken as a model compound, where quantum simulations of the spectra are directly coupled with molecular dynamics (MD) techniques. Such a multiscale approach reveals how the structural information is encoded in the broadened spectral lines. The spectra were simulated for solvent-solute clusters generated by MD. Conformational averaging was enabled by a limited library of conformers for which the spectral parameters could be calculated ab initio and moved on the MD geometries by Cartesian coordinate tensor transfer techniques. The B3LYP/CPCM/6-31+G** approximation was used as a default for computation of the source force fields and polarizability derivatives. The spectra thus obtained relatively faithfully reproduced most of the experimental features. The Amber and polarizable Amoeba MD force fields produced similar results; application of the latter, however, was limited by the long time necessary to achieve a converged conformational equilibrium. Both MD simulation and spectral averaging suggest that the hydroxyl groups as well as the backbone C-C bonds rotate relatively freely, with some restrictions in the vicinity of the carboxyl group. In spite of the averaging, spectral response of characteristic vibrational normal mode families, such as CH and OH bending, can clearly be identified in the spectra. The simulations thus confirm the experimental fact that flexible saccharides exhibit significant vibrational activity that reveals precious information about molecular structure and dynamics encoded in the Raman and ROA spectral shapes.

Monitoring the Backbone Conformation of Valinomycin by Raman Optical Activity

“…Previous analyses of similar flexible molecules [11,41,56,57] suggest that the broadened ROA peaks of the free form probably accompany many conformational species of valinomycin in solution.…”

“…This methodology has been successfully applied to simulations of both vibrational circular dichroism (VCD) [39,40] and ROA [12,19] spectra, including ROA of flexible molecules. [41][42][43] A database of characteristic fragments can be used for many conformers with a similar structure. [41] The B3LYP [44] functional was previously used to calculate accurate force field and polarizability tensors of valinomycin.…”

“…[41][42][43] A database of characteristic fragments can be used for many conformers with a similar structure. [41] The B3LYP [44] functional was previously used to calculate accurate force field and polarizability tensors of valinomycin. [19] In this study, we used the similar B3PW91 [45] functional, which better reproduces some minor spectral features, such as the methyl deformation ROA band at about 1460 cm À1 and lowfrequency region of extended amide III ROA bands at about 1390 cm…”

“…Combining MD and quantum mechanical calculations was found to be beneficial for small molecules in solution which exhibit similar flexible structure to valinomycin. [19,41,43] The ROA and Raman tensors and the force field of the P1 conformer were transferred to 17 MD geometries of the propeller Figure 4. Calculated ROA (top) and Raman (bottom) spectra of the bracelet conformers of free valinomycin (sB1, sB2, asB1, and asB2; see Supporting Information for structural details) and the experimental spectra in dioxane.…”

Conformational analyses of peptides and proteins by vibrational Raman optical activity

“…ROA is measured as tiny differences in Raman scattering intensities corresponding to right and left circularly polarized light [1][2][3][4][5]. Analysis of the ROA spectrum can provide not only the absolute configuration of a molecule [6,7], but also the detailed conformation accompanying the vibrational motions of the molecules [8][9][10][11][12][13][14][15][16][17][18][19][20], which are not accessible by the other methods [2]. ROA intensity is generated not only by the electric dipole-electric dipole polarizability (α), but also the electric dipole-magnetic dipole (G) and the electric dipole-electric quadrupole (A′) polarizabilities [2,3,21].…”