(1)H-NMR as a Structural and Analytical Tool of Intra- and Intermolecular Hydrogen Bonds of Phenol-Containing Natural Products and Model Compounds

Experimental parameters that influence the resolution of (1)H-NMR phenol OH signals are critically evaluated with emphasis on the effects of pH, temperature and nature of the solvents. Extremely sharp peaks (Δν(1/2) ≤ 2 Hz) can be obtained under optimized experimental conditions which allow the application of (1)H-(13)C HMBC-NMR experiments to reveal long range coupling constants of hydroxyl protons and, thus, to provide unequivocal assignment of the OH signals even in cases of complex polyphenol natural products. Intramolecular and intermolecular hydrogen bonds have a very significant effect on (1)H OH chemical shifts which cover a region from 4.5 up to 19 ppm. Solvent effects on –OH proton chemical shifts, temperature coefficients (Δδ/ΔT), OH diffusion coefficients, and (n)J((13)C, O(1)H) coupling constants are evaluated as indicators of hydrogen bonding and solvation state of phenol –OH groups. Accurate (1)H chemical shifts of the OH groups can be calculated using a combination of DFT and discrete solute-solvent hydrogen bond interaction at relatively inexpensive levels of theory, namely, DFT/B3LYP/6-311++G (2d,p). Excellent correlations between experimental (1)H chemical shifts and those calculated at the ab initio level can provide a method of primary interest in order to obtain structural and conformational description of solute-solvent interactions at a molecular level. The use of the high resolution phenol hydroxyl group (1)H-NMR spectral region provides a general method for the analysis of complex plant extracts without the need for the isolation of the individual components.