A simple and fast method of measuring hydrogen-bond-accepting abilities for a wide variety of organic compounds was previously developed in our lab using 19F and 31P NMR spectroscopy with the inexpensive and commercially available probes, pentafluorobenzoic acid (PFBA) and phenylphosphinic acid (PPA). In our prior studies, dichloromethane was used as the solvent for its lack of interference with the H-bonding interactions and approximation of a more hydrophobic protein binding environment. Herein we describe the use of more polar solvents as models of biological environments to improve and expand this method. Based on a series of polar solvents examined, chloroform and acetone were chosen as good solvents due to its commercial availability, cost, solubility in PPA and PFBA, and quality of NMR data. The measured △δ(31P) and △δ(19F) values in acetone and chloroform demonstrated high correlation with Hammett parameters of HBAs, pKa of protonated hydrogen bond acceptors, and proton transfer basicity. Using acetone was also able to expand the scope of HBAs and include more scaffolds of medicinally relevant and naturally occurring polar hydrogen bonding compounds.

NMR quantification of hydrogen-bond-accepting ability for organic molecules in polar solvents

ACS Spring 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.