Water Solvent Effect on Theoretical Evaluation of 1 H NMR Chemical Shifts: o-Methyl-Inositol Isomer.

In this paper, density functional theory calculations of nuclear magnetic resonance (NMR) chemical shifts for l-quebrachitol isomer, previously studied in our group, are reported with the aim of investigating in more detail the water solvent effect on the prediction of1 H NMR spectra. In order to include explicit water molecules, 20 water-l-quebrachitol configurations obtained from Monte Carlo simulation were selected to perform geometry optimizations using the effective fragment potential method encompassing 60 water molecules around the solute. The solvated solute optimized geometries were then used in B3LYP/6-311+G(2d,p) NMR calculations with PCM-water. The inclusion of explicit solvent in the B3LYP NMR calculations resulted in large changes in the1 H NMR profiles. We found a remarkable improvement in the agreement with experimental NMR profiles when the explicit hydrated l-quebrachitol structure is used in B3LYP1 H NMR calculations, yielding a mean absolute error (MAE) of only 0.07 ppm, much lower than reported previously for the gas phase optimized structure (MAE = 0.11 ppm). In addition, a very improved match between theoretical and experimental1 H NMR spectrum measured in D2 O was achieved with the new hydrated optimized l-quebrachitol structure, showing that a fine-tuning of the theoretical NMR spectra can be accomplished once solvent effects are properly considered.