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The (1)H NMR chemical shifts, coupling constants, temperature coefficients, and exchange rates have been measured for the hydroxy protons of aqueous solutions of alpha-, beta-, and gamma-cyclodextrins, maltose, and maltoheptaose. In cyclodextrins (CDs), the high chemical shift of the O(3)H signal and its small (3)J(OH,CH) value suggest that O(3)H is involved in a hydrogen bond. The small temperature coefficients and rate of exchange values of O(2)H and O(3)H confirm the involvement of O(3)H in hydrogen bonding and indicate that O(2)H is the hydrogen bond partner. In maltose, two distinct NMR signals with two different vicinal coupling constants are found for O(2')H. A cross-peak in the ROESY spectrum indicates chemical exchange between the O(2')H and O(3)H protons. The existence of two distinct NMR signals with different J values for O(2')H shows the influence of anomeric configuration on the O(2')H-O(3)H interaction. The effect of complexation with methyl benzoate, adamantane-1-carboxylic acid, adamantane-1-ol, and l- and d-tryptophane on the NMR spectra of the hydroxy protons of alpha-, beta-, and gamma-cyclodextrins and of maltose has been investigated. No significant spectral changes were observed upon addition of methyl benzoate and adamantane-1-carboxylic acid. The addition of adamantane-1-ol resulted in an upfield shift and a strong broadening of the O(2)H signal from alpha-CD, and a small temperature coefficient was measured upon complexation. The O(2)H and O(3)H signals in beta-CD were broadened and shifted downfield upon addition of l- and d-tryptophane.

The solution conformations of aristeromycin (1), 2‘-deoxyaristeromycin (2), and 3‘-deoxyaristeromycin (3) have been determined from an integrated analysis of X-ray (for 1 only), NMR data (i.e., 3 J HH coupling constants), and ab initio calculations. One-dimensional NOE difference experiments showed that the adenin-9-yl ring in 1 and 2 is involved in a ∼50% syn ⇄ ∼50% anti equilibrium around the C-glycosyl torsion angle, whereas an anti orientation (χ = −113°) is found in the X-ray crystal structure of 1. The preferred conformation around the γ torsion angle is γt both in solution for 1−3 and in the solid state (for 1 only). The plots of energy as a function of the phase angle of pseudorotation (Figure ) for the structures optimized by ab initio calculations (HF/3-21G*) show that there are two major wells of low energy conformers for 1−3, supporting the two-state North-type ⇄ South/West-type equilibrium of the constituent cyclopentane rings in 1−3. The ab initio calculations suggested that the South/West-type conformers are more stable than the North-type forms for 1 [ΔE (120° < P < 240°) − (330° < P < 30°) ∼10 kcal/mol], for 2 [ΔE (210° < P < 240°) − (330° < P < 60°) ∼ 4 kcal/mol] and for 3 [ΔE (P = 240°) − (330° < P < 0°) ∼ 6 kcal/mol]. Newly developed A and B sets of parameters correlating the H−C−C−H torsions to the endocyclic torsions based on the ab initio optimised structures of 1−3 have been subsequently used to interpret the time-averaged 3 J HH couplings using the program PSEUROT. The discrepancy found between the X-ray crystal structure (P = 89°, Ψm = 41°) of aristeromycin (1) and its structure calculated by NMR-PSEUROT conformational analysis (35° < P [ T − T] < 65°, 35° < Ψm < 45°) ⇄ (128° < P [1E] < 131°, 34° < Ψm < 36°) based on observed 3 J HH couplings in aqueous solution, as well as the relatively high error in the NMR-PSEUROT analyses for 1−3 [ΔJ max ≤ 1.6 Hz (i.e., maximal difference between experimental and PSEUROT-calculated 3 J HH) and root mean square (rms) error ≤ 0.7 Hz] prompted us to reparametrize the Karplus equation implemented in the PSEUROT program by using torsion angles derived from solid-state geometries of conformationally constrained nucleosides and their corresponding experimental 3 J HH. The precision of our reparametrized Karplus-type equation (rms error = 0.40 Hz) became comparable to that expected for the standard Haasnoot−Altona Karplus (0.48 Hz) equation. The results of the PSEUROT analyses performed with the standard Haasnoot−Altona Karplus equation are also very comparable in terms of geometry with those based on our reparametrized equation (eq 4). Both series of PSEUROT analyses suggest that the predominant conformation of the cyclopentane ring in 1−3 is defined by 128° < P < 140° for 1, 105° < P < 116° for 2, and 118° < P < 127° for 3, with the puckering amplitude in the range from 34° to 40° for 1−3. However, PSEUROT analyses based on our Karplus equation produced a smaller rms error by ≤0.14 Hz and ΔJ max error by ≤0.5 Hz than those performed with the standard...

Density functional theory (DFT) and Hartree-Fock (HF) quantum mechanical calculations have been performed on the disaccharides, [small beta]-l-Fucp-(1[rightward arrow]4)-[small alpha]-d-Galp-OMe, [small beta]-l-Fucp-(1[rightward arrow]4)-[small alpha]-d-Glcp-OMe, and [small beta]-l-Fucp-(1[rightward arrow]3)-[small alpha]-d-Glcp-OMe. The [capital Delta][small delta]-values (difference between the chemical shift in the disaccharide and the corresponding monosaccharide methyl glycoside) for the exchangeable hydroxy protons have been calculated and compared to experimental values previously measured by NMR spectroscopy for samples in aqueous solutions. The calculations performed on molecules in vacuum showed that hydroxy protons hydrogen bonded to the neighboring ring oxygens have large positive [capital Delta][small delta]-values, indicating that they are deshielded relative to those in the corresponding methyl glycoside. The NMR experiments showed instead that these hydroxy protons close to the neighboring ring oxygens were shielded. This discrepancy between calculated and experimental data was attributed to solvent effects, and this hypothesis has been confirmed in this work by monitoring the chemical shift of the hydroxy proton of methanol in water, ethers and water/ether solutions. Shielding of the hydroxy proton of methanol is observed for increased ether concentrations, whereas deshielding is observed for increased concentration of water. The shielding observed for hydroxy protons in disaccharides is a consequence of reduced hydration due to intermolecular hydrogen bonding or steric effects. In strongly hydrated systems such as carbohydrates, the hydration state of a hydroxy proton is the key factor determining the value of the chemical shift of its NMR signal, and the [capital Delta][small delta] will be a direct measure of the change in hydration state.