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

Abstract

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 of 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 theH NMR profiles. We found a remarkable improvement in the agreement with experimental NMR profiles when the explicit hydrated l-quebrachitol structure is used in B3LYP 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 experimentalH NMR spectrum measured in DO 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.

Structural Determination of Antioxidant and Anticancer Flavonoid Rutin in Solution through DFT Calculations of 1H NMR Chemical Shifts

“…The agreement with experimental 1 H NMR signals for rutin lateral chain protons could be improved using explicit solvent molecules as reported in Ref. for l ‐quebrachitol, where 50 water molecules surrounded the solute embedded in a continuum model (PCM). Such approach involves a high computational demand and according to the results from Ref.…”

“…Such approach involves a high computational demand and according to the results from Ref. is not strictly necessary. It was found that the PCM model provides a very reasonable account of the solvent effect on the calculation of NMR spectra for organic molecules.…”

“…Detailed analysis of NMR chemical shifts may provide specific information regarding molecular structure . Molecular modeling associated with density functional theory (DFT) has been widely employed by our group in studies at the molecular level of the action mechanism of potential drugs candidates for the treatment of cancer and other diseases. De Souza et al .…”

A DFT study of molecular structure and 1H NMR, IR, and UV‐Vis spectrum of Zn(II)‐kaempferol complexes: A metal‐flavonoid complex showing enhanced anticancer activity

“…The agreement with experimental 1 H NMR spectrum measured in solution can be improved with the use of explicit solvent molecules in the B3LYP NMR calculation, as reported in Ref. , where 50 water solvent molecules surrounding the l ‐quebrachitol solute was used in conjunction with the PCM model to better describe the solvent effect. Such approach precisely represents solute‐solvent interactions, however involves a high computational demand.…”

“…From the results reported in Ref. , it can be seen that such more elaborate procedure is not strictly necessary, with the PCM continuum model providing a satisfactory description of the solvent effect on the calculation of NMR spectra for structural determination of organic molecules.…”