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

• Published in: Journal of chemical information and modeling Vol. 59; no. 9; pp. 3735 - 3743
• Main Author: Bauer, Christoph A
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 23.09.2019
• Subjects: Alcohols; Bonding strength; Chemical bonds; Computation; Density functional theory; First principles; Free energy; Hydrogen bonding; Hydrogen bonds; Mean square errors; NMR; Nuclear magnetic resonance; Organic chemistry; Quantum chemistry; Root-mean-square errors; Solvation
• ISSN: 1549-9596; 1549-960X
• DOI: 10.1021/acs.jcim.9b00132

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 R 2 = 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 R 2 = 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.