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dc.contributor.authorKasireddy, Chandana
dc.contributor.authorBann, James G.
dc.contributor.authorMitchell-Koch, Katie R.
dc.identifier.citationKasireddy, Chandana; Bann, James G.; Mitchell-Koch, Katie R. 2015. Demystifying fluorine chemical shifts: electronic structure calculations address origins of seemingly anomalous 19F-NMR spectra of fluorohistidine isomers and analogues. Phys. Chem. Chem. Phys., 2015,17, 30606-30612 DOI: 10.1039/C5CP05502Den_US
dc.descriptionClick on the DOI link to access the article (may not be free).en_US
dc.description.abstractFluorine NMR spectroscopy is a powerful tool for studying biomolecular structure, dynamics, and ligand binding, yet the origins of F-19 chemical shifts are not well understood. Herein, we use electronic structure calculations to describe the changes in 19F 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 19F 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.en_US
dc.description.sponsorshipFinancial support for the work comes from Wichita State University, Fairmount College of Liberal Arts and Sciences and K-INBRE startup funds under NIH National Institute of General Medical Sciences, P20 GM103418. Computing resources were funded by the National Science Foundation under Grant No. EIA-0216178 and EPS-0236913, with matching support from the State of Kansas and the Wichita State University High Performance Computing Center.en_US
dc.publisherRoyal Society of Chemistryen_US
dc.relation.ispartofseriesPhysical Chemistry Chemical Physics;v.17:no.45
dc.subjectColi dihydrofolate-reductaseen_US
dc.titleDemystifying fluorine chemical shifts: electronic structure calculations address origins of seemingly anomalous F-19-NMR spectra of fluorohistidine isomers and analoguesen_US
dc.rights.holder© Royal Society of Chemistry 2016en_US

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