Density Functional Study of the Conformational Space of ⁴C₁ d-Glucuronic Acid

Abstract

The conformational space of (4)C(1) alpha- and beta-d-glucuronic acid was scanned by HF/3-21G(p) calculations followed by optimization of the 15 most stable structures for each, using the B3LYP density functional theory method in conjunction with a diffuse polarized valence triple-zeta basis set. We found a general preference of the alpha anomers in the isolated molecules in agreement with the large endo-anomeric hyperconjugation effects in these structures. From the other intramolecular interactions (exo-anomeric hyperconjugation, hydrogen-bonding, dipole-dipole, and steric interactions), the effect of the hydrogen bonding is the most pronounced and plays a major role in determining the stability order within the alpha and beta series. The most stable conformer of both alpha and beta (4)C(1) d-glucuronic acid is the structure with the maximum number (5) of intramolecular hydrogen bonds. Introduction of solvent (water) effects by the SCI-PCM model resulted in two characteristic changes of the energetic properties: the gas-phase stability order changed considerably, and the energy range of the 15 most stable conformers decreased from 30 to 15 kJ/mol. The geometrical parameters reflect well the superimposed effects of hyperconjugation and hydrogen-bonding interactions. Most characteristics are the variations of the C-O bond distances (within a range of 0.04 A) upon the combined intramolecular effects.

Efficient Construction of Atomic-Resolution Models of Non-Sulfated Chondroitin Glycosaminoglycan Using Molecular Dynamics Data

“…To validate this simple approach to assigning ring pucker geometry, we computed C-P parameters of each monosaccharide ring in the MD-simulated 20-mer ensemble (10 * 40,000 = 400,000 ring conformations for each of the two monosaccharide types). As seen in NMR and force-field studies, the stable 4 C 1 chair ring pucker was the principal conformer for both GlcA [50,[96][97][98][99] and GalNAc [46,96,98,100] in the MD simulations, with slight deformations (0 • < C-P θ < 30 • ) (Figure 4a,b). However, a small minority of GlcA ring conformers were skew-boat or boat, namely 3 S 1 , B 1,4 , 5 S 1 , 2,5 B, 2 S O , B 3,O , 1 S 3 , 1,4 B, and 1 S 5 (60 • < C-P θ < 120 • ) (Figure 4b).…”

Constructing 3-Dimensional Atomic-Resolution Models of Nonsulfated Glycosaminoglycans with Arbitrary Lengths Using Conformations from Molecular Dynamics

“…C-P analysis of GlcA monosaccharide rings in the hyaluronan 20-mer showed that GlcA is found mostly in 4 C 1 chair conformations ( Figure 3 b), as seen in crystal structures [ 92 , 93 , 94 , 95 ] and NMR and force field studies [ 51 , 67 , 101 , 102 , 107 , 109 , 110 ], with some boat and skew-boat conformations, including 3 S 1 , B 1,4 , 5 S 1 , 2,5 B, 2 S O , 1 S 3 , 1,4 B, and 1 S 5 ( Figure 3 b and Figure 4 b,c), which were also observed in GlcA rings in unbiased MD simulations of nonsulfated chondroitin 20-mers [ 33 ]. Some of these conformations were also sampled rarely in unbiased MD simulations of GlcA monosaccharides [ 51 , 107 ].…”

Synthesis and conformational analysis of methyl 3-amino-2,3-dideoxyhexopyranosiduronic acids, new sugar amino acids, and their diglycotides

“…The DFT calculations of the conformational space of D D-glucuronic acid in the 4 C 1 conformation demonstrate that repulsion of the carbonyl oxygen and ring oxygen lone pairs strongly determines the rotational preferences of the carboxyl group. 29 It seems that this repulsion should be stronger in the 4 C 1 than in the 1 C 4 conformation. This statement results from the fact that dipole of the ring oxygen lone pairs is oriented parallel to the C-5-H bond in the 1 C 4 conformation, whereas the same dipole in the 4 C 1 form is oriented parallel to the C-5-CO bond.…”