How to Model Inter- and Intramolecular Hydrogen Bond Strengths with Quantum Chemistry

This article presents the computation of both inter- and intramolecular hydrogen bond strengths from first-principles. Quantum chemical calculations conducted at the dispersion-corrected density functional theory level including free energy and solvation contributions are conducted for (i) one-to-one hydrogen-bonded complexes of alcohols to N-methyl pyrrolidinone measured by an infrared spectroscopy method and (ii) a set of experimental intramolecular hydrogen bond-forming phenol and pyrrole compounds, with intramolecular hydrogen bond strengths derived from a nuclear magnetic resonance method. The computed complexation free energies in solution show a correlation to experiment of R2 = 0.74 with a root mean square error of 4.85 kJ mol–1. The intramolecular hydrogen bonding free energies in solution show a correlation of R2 = 0.79 with a root mean square error of 5.51 kJ mol–1. The results of this study can be used as a guide on how to build reliable quantum chemical databases for computed hydrogen bonding strengths.