Demystifying fluorine chemical shifts: electronic structure calculations address origins of seemingly anomalous 19F-NMR spectra of fluorohistidine isomers and analogues. Issue 45 (2nd November 2015)

• Record Type: Journal Article
• Authors: Kasireddy, Chandana; Bann, James G.; Mitchell-Koch, Katie R.
• Is Part Of: Physical chemistry chemical physics. Volume 17:Issue 45(2015)
• Page Start: 30606
• Page End: 30612
• Publication Date: 2015-11-02
• Subjects: Chemistry, Physical and theoretical -- Periodicals; 541.3
• DOI: 10.1039/c5cp05502d
• Languages: English
• ISSNs: 1463-9076

Abstract

Abstract : Understanding localization/delocalization of fluorine electron density is shown to be critical for predicting and interpreting fluorine chemical shift. Abstract : Fluorine NMR spectroscopy is a powerful tool for studying biomolecular structure, dynamics, and ligand binding, yet the origins of 19 F chemical shifts are not well understood. Herein, we use electronic structure calculations to describe the changes in 19 F chemical shifts of 2F- and 4F-histidine/(5-methyl)-imidazole upon acid titration. While the protonation of the 2F species results in a deshielded chemical shift, protonation of the 4F isomer results in an opposite, shielded chemical shift. The deshielding of 2F-histidine/(5-methyl)-imidazole upon protonation can be rationalized by concomitant decreases in charge density on fluorine and a reduced dipole moment. These correlations do not hold for 4F-histidine/(5-methyl)-imidazole, however. Molecular orbital calculations reveal that for the 4F species, there are no lone pair electrons on the fluorine until protonation. Analysis of a series of 4F-imidazole analogues, all with delocalized fluorine electron density, indicates that the deshielding of 19 F chemical shifts through substituent effects correlates with increased C–F bond polarity. In summary, the delocalization of fluorine electrons in the neutral 4F species, with gain of a lone pair upon protonation may help explain the difficulty in developing a predictive framework for fluorine chemical shifts. Ideas debated by chemists over 40 years ago, regarding fluorine's complex electronic effects, are shown to have relevance for understanding and predicting fluorine NMR spectra.