To Gibbs or Not to Gibbs Effect of Entropic Contribution in the NMR Calculations of Flexible and Polar Molecules-Updating the DP4+App.

Abstract

The application of quantum-based NMR methods for the structural elucidation of natural and unnatural products has grown significantly. However, accurately calculating the conformational landscape of flexible molecules with intricate intramolecular hydrogen bonding (IHB) networks continues to be a major challenge. In this work, we thoroughly studied the effect of entropic contributions (trough Gibbs free energies calculations) in the DP4+ performance. Our results show that to solve biased systems with strong IHB interactions requires computing the Boltzmann contributions using Gibbs free energies computed with at least triple-ξ basis set and SMD solvation model. In response to this finding, we have updated our DP4+App, a user-friendly Python applet that automates the entire process of calculating DP4+ probabilities. In the new version, the program allows for calculating of conformational contributions at any selected theory level, using either SCF or Gibbs free energies.