Methyl β-lactoside [methyl β-D-galactopyranosyl-(1→4)-β-D-glucopyranoside] monohydrate, C 13 H 24 O 11 ·H 2 O, (I), was obtained via spontaneous transformation of methyl β-lactoside methanol solvate, (II), during air-drying. Cremer–Pople puckering parameters indicate that the β-D-Gal p (β-D-galactopyranosyl) and β-D-Glc p (β-D-glucopyranosyl) rings in (I) adopt slightly distorted 4 C 1 chair conformations, with the former distorted towards a boat form ( B C1,C4 ) and the latter towards a twist-boat form ( O5 S C2 ). Puckering parameters for (I) and (II) indicate that the conformation of the βGal p ring is slightly more affected than the βGlc p ring by the solvomorphism. Conformations of the terminal O -glycosidic linkages in (I) and (II) are virtually identical, whereas those of the internal O -glycosidic linkage show torsion-angle changes of 6° in both C—O bonds. The exocyclic hydroxymethyl group in the βGal p residue adopts a gt conformation (C4′ anti to O6′) in both (I) and (II), whereas that in the βGlc p residue adopts a gg ( gauche – gauche ) conformation (H5 anti to O6) in (II) and a gt ( gauche – trans ) conformation (C4 anti to O6) in (I). The latter conformational change is critical to the solvomorphism in that it allows water to participate in three hydrogen bonds in (I) as opposed to only two hydrogen bonds in (II), potentially producing a more energetically stable structure for (I) than for (II). Visual inspection of the crystalline lattice of (II) reveals channels in which methanol solvent resides and through which solvent might exchange during solvomorphism. These channels are less apparent in the crystalline lattice of (I).
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Two-bond 13 C– 13 C spin-coupling constants in saccharides: dependencies on exocyclic hydroxyl group conformation
Seven doubly 13 C-labeled isotopomers of methyl β- d -glucopyranoside, methyl β- d -xylopyranoside, methyl β- d -galactopyranoside, methyl β- d -galactopyranosyl-(1→4)-β- d -glucopyranoside and methyl β- d -galactopyranosyl-(1→4)-β- d -xylopyranoside were prepared, crystallized, and studied by single-crystal X-ray crystallography and solid-state 13 C NMR spectroscopy to determine experimentally the dependence of 2 J C1,C3 values in aldopyranosyl rings on the C1–C2–O2–H torsion angle, θ 2 , involving the C2 carbon of the C1–C2–C3 coupling pathway. Using X-ray crystal structures to determine θ 2 in crystalline samples and by selecting compounds that exhibit a relatively wide range of θ 2 values in the crystalline state, 2 J C1,C3 values measured in crystalline samples were plotted against θ 2 and the resulting plot compared to that obtained from density functional theory (DFT) calculations. For θ 2 values ranging from ∼90° to ∼240°, very good agreement was observed between the experimental and theoretical plots, providing strong validation of DFT-calculated spin-coupling dependencies on exocyclic C–O bond conformation involving the central carbon of geminal C–C–C coupling pathways. These findings provide new experimental evidence supporting the use of 2 J CCC values as non-conventional spin-coupling constraints in MA′AT conformational modeling of saccharides in solution, and the use of NMR spin-couplings not involving coupled hydroxyl hydrogens as indirect probes of C–O bond conformation. Solvomorphism was observed in crystalline βGal-(1→4)-βGlcOCH 3 wherein the previously-reported methanol solvate form was found to spontaneously convert to a monohydrate upon air-drying, leading to small but discernible conformational changes in, and a new crystalline form of, this disaccharide.
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- Award ID(s):
- 2002625
- PAR ID:
- 10329743
- Date Published:
- Journal Name:
- Physical Chemistry Chemical Physics
- Volume:
- 23
- Issue:
- 40
- ISSN:
- 1463-9076
- Page Range / eLocation ID:
- 22912 to 22922
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Two disaccharides, methyl β-d-galactopyranosyl-(1→4)-α-d-glucopyranoside (1) and methyl β-d-galactopyranosyl-(1→4)-3-deoxy-α-d-ribo-hexopyranoside (3), were prepared with selective 13C-enrichment to allow measurement of six trans-O-glycosidic J-couplings (2JCOC, 3JCOCH, and 3JCOCC) in each compound. Density functional theory (DFT) was used to parameterize Karplus-like equations that relate these J-couplings to either ϕ or ψ. MA’AT analysis was applied to both linkages to determine mean values of ϕ and ψ in each disaccharide and their associated circular standard deviations (CSDs). Results show that deoxygenation at C3 of 1 has little effect on both the mean values and librational motions of the linkage torsion angles. This finding implies that, if inter-residue hydrogen bonding between O3H and O5′ of 1 is present in aqueous solution and persistent, it plays little if any role in dictating preferred linkage conformation. Hydrogen bonding may lower the energy of the preferred linkage geometry but does not determine it to any appreciable extent. Aqueous 1-μs MD simulation supports this conclusion and also indicates greater conformational flexibility in deoxydisaccharide 3 in terms of sampling several, conformationally distinct, higher-energy conformers in solution. The populations of these latter conformers are low (3–14%) and could not be validated by MA’AT analysis. If the MD model is correct, however, C3 deoxygenation does enable conformational sampling over a wider range of ϕ/ψ values, but linkage conformation in the predominant conformer is essentially identical in both 1 and 3.more » « less
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Isopropyl 3-deoxy-α-D- ribo -hexopyranoside (isopropyl 3-deoxy-α-D-glucopyranoside), C 9 H 18 O 5 , (I), crystallizes from a methanol–ethyl acetate solvent mixture at room temperature in a 4 C 1 chair conformation that is slightly distorted towards the C5 S C1 twist-boat form. A comparison of the structural parameters in (I), methyl α-D-glucopyranoside, (II), α-D-glucopyranosyl-(1→4)-D-glucitol (maltitol), (III), and 3-deoxy-α-D- ribo -hexopyranose (3-deoxy-α-D-glucopyranose), (IV), shows that most endocyclic and exocyclic bond lengths, valence bond angles and torsion angles in the aldohexopyranosyl rings are more affected by anomeric configuration, aglycone structure and/or the conformation of exocyclic substituents, such as hydroxymethyl groups, than by monodeoxygenation at C3. The structural effects observed in the crystal structures of (I)–(IV) were confirmed though density functional theory (DFT) calculations in computed structures (I) c –(IV) c . Exocyclic hydroxymethyl groups adopt the gauche – gauche ( gg ) conformation (H5 anti to O6) in (I) and (III), and the gauche – trans ( gt ) conformation (C4 anti to O6) in (II) and (IV). The O -glycoside linkage conformations in (I) and (III) resemble those observed in disaccharides containing β-(1→4) linkages.more » « less
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The crystal structures of 2,3,4,6-tetra- O -benzoyl-β-D-galactopyranosyl-(1→4)-1,2,6-tri- O -benzoyl-β-D-glucopyranose ethyl acetate hemisolvate, C 61 H 50 O 18 ·0.5C 4 H 8 O 2 , and 1,2,4,6-tetra- O -benzoyl-β-D-glucopyranose acetone monosolvate, C 34 H 28 O 10 ·C 3 H 6 O, were determined and compared to those of methyl β-D-galactopyranosyl-(1→4)-β-D-glucopyranoside (methyl β-lactoside) and methyl β-D-glucopyranoside hemihydrate, C 7 H 14 O 6 ·0.5H 2 O, to evaluate the effects of O -benzoylation on bond lengths, bond angles and torsion angles. In general, O -benzoylation exerts little effect on exo- and endocyclic C—C and endocyclic C—O bond lengths, but exocyclic C—O bonds involved in O -benzoylation are lengthened by 0.02–0.04 Å depending on the site of substitution. The conformation of the O -benzoyl side-chains is highly conserved, with the carbonyl O atom either eclipsing the H atom attached to a 2°-alcoholic C atom or bisecting the H—C—H bond angle of an 1°-alcoholic C atom. Of the three bonds that determine the side-chain geometry, the C—O bond involving the alcoholic C atom exhibits greater rotational variability than the remaining C—O and C—C bonds involving the carbonyl C atom. These findings are in good agreement with recent solution NMR studies of the O -acetyl side-chain conformation in saccharides.more » « less
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/d1cp03320d
