Vacuum Ultraviolet Electronic Circular Dichroism Study of d-Glucose in Aqueous Solution

Abstract

Vacuum ultraviolet (VUV) electronic circular dichroism (ECD) spectra of d-glucose, α-d-glucopyranose, and β-d-glucopyranose were measured in aqueous solution down to 163 nm using a synchrotron radiation VUV-ECD spectrophotometer and theoretically analyzed using molecular dynamics (MD) simulations with explicit water molecules and using time-dependent density functional theory (TDDFT). The theoretically calculated spectra reproduced the experimentally observed spectra well, revealing that VUV-ECD exhibited unique spectra depending on the α-anomer and β-anomer configurations of the hydroxyl group at C-1 and the three gauche (G) and trans (T) rotamer conformations (GT, GG, and TG) of the hydroxymethyl group at C-5. These unique spectra could be ascribed to differences in the patterns of intramolecular hydrogen bonds around the hydroxymethyl group at C-5 for the three rotamers and around the hydroxyl group at C-1 for the two anomers. The strengths of these intramolecular interactions increased as the degree of hydration around the corresponding chromophores decreased, suggesting that hydration is a key factor for stabilizing rotamer and anomer structures. The rotamerization and anomerization mechanisms are further discussed in terms of differences in the intramolecular interactions and the degree of hydration among the rotamer and anomer structures. The findings demonstrate that VUV-ECD spectroscopy is a useful tool for characterizing the equilibrium structures of monosaccharides.

Theoretical–Computational Modeling of CD Spectra of Aqueous Monosaccharides by Means of Molecular Dynamics Simulations and Perturbed Matrix Method

“…In this section, we focused our attention on the results concerning the modeling of the ECD spectrum, and therefore, we did not discuss the MD details used as they were not strictly related to the focus of this study. It would be sufficient for us to state that the conformational analysis, conducted on our simulations for D-glucose, produced similar results, as compared to those reported in the literature [39] on this widely investigated system [40][41][42][43][44].The results of the present study are entirely based on a theoretical framework, termed as MD-PMM, which has been extensively reported in our previous works [26,27,[31][32][33]45] and here briefly reviewed. The method requires a preliminary MD simulation of the system of interest, e.g., a chromophore surrounded by the solvent molecules.…”

“…For the sake of clarity, we have also reported, in the same figure, the mean values of the O6-C-C-O5 dihedral angle for the hydroxymethyl rotation (Figure 1) as a function of the same two-dimensional (essential) plane position, as obtained by the MD-free (note that according to our definition, GT, GG, and TG correspond to the dihedral angle approximately equal to 180 • , 60 • /240 • , and 0 • , respectively.) Results reported in the figure show that, in good agreement with experimental estimations and even with recent simulations [39] on the same system, the probability of the TG state was negligible and that Alpha-GT:Alpha-GG = 42:58 and Beta-GT:Beta-GG = 40:60.…”

“…The maximum of the global ECD spectrum was found at 174 nm, i.e., 6 nm red-shift with respect to the experimental value. This result was probably due to the intrinsic limitations of the CAM-B3LYP functional that had provided the same shift in the study of Matsuo and Gekko [39]. Not surprisingly, for cases such as the present one in which the vibronic effect had not been taken into account and where we had used the vertical transition approximation [45], the absolute intensity was overestimated, though the correct order-of-magnitude of the experimental spectral intensity [35] was reproduced.…”

“…Based on the comparison of the calculated spectra with the available experimental data [35,39], we could draw the following conclusions.…”

“…For this purpose, we have selected a particularly challenging and well-investigated topic represented by the reconstruction and interpretation of the ECD spectrum of two monosaccharides in an aqueous solution, namely D-glucose and D-galactose (Figure 1). The ECD spectrum of D-glucose, i.e., the spectrum of alpha-D-glucopyranose (hereafter, Alpha-Glu) and beta-D-glucopyranose (hereafter Beta-Glu), has already been the focus of a large number of studies [34][35][36][37][38], and it has been recently reappraised by a joint experimental and computational study based on the calculation of the spectral signal using 40 structures extracted from an MD simulation, with the continuum dielectric mimicking the solvent effect [39]. Such a study, which successfully reproduced the experimental data, had in fact clearly demonstrated the very strong dependency of the ECD signal on D-glucose stereochemical features, in particular: (i) the alpha and beta configurations; (ii) the gauche (G) and trans (T) conformations generated by the torsion motion involving the hydroxymethyl group and pyranoside oxygen (i.e., the O6-C-C-O5 dihedral angle in Figure 1), producing three different states termed as GG, GT, and TG; and finally, (iii) the different rotamers associated with the torsions of all the hydroxyl groups.…”