Dissecting Solvent Effects on Hydrogen Bonding

Angew Chem Int Ed Engl. 2022 Jul 25;61(30):e202206604. doi: 10.1002/anie.202206604. Epub 2022 Jun 14.

Abstract

The experimental isolation of H-bond energetics from the typically dominant influence of the solvent remains challenging. Here we use synthetic molecular balances to quantify amine/amide H-bonds in competitive solvents. Over 200 conformational free energy differences were determined using 24 H-bonding balances in 9 solvents spanning a wide polarity range. The correlations between experimental interaction energies and gas-phase computed energies exhibited wild solvent-dependent variation. However, excellent correlations were found between the same computed energies and the experimental data following empirical dissection of solvent effects using Hunter's α/β solvation model. In addition to facilitating the direct comparison of experimental and computational data, changes in the fitted donor and acceptor constants reveal the energetics of secondary local interactions such as competing H-bonds.

Keywords: Electrostatic Interactions; Hydrogen Bonds; Noncovalent Interactions; Solvent Effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides*
  • Hydrogen Bonding
  • Solvents / chemistry
  • Thermodynamics

Substances

  • Amides
  • Solvents