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Understanding fluorine chemical shifts and the molecular properties of organic molecules
Kasireddy, Chandana
Kasireddy, Chandana
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dissertation
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2018-05
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Electronic dissertations
Electronic dissertations
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Abstract
Fluorinated molecules have emerged as important probes in drug design, and as strategies
for enhancing protein stability and altering physicochemical properties of biological
systems. Fluorine NMR plays a crucial role in studying protein structure, dynamics and
protein-ligand interactions. Histidine is an important amino acid involved in many
enzymatic reactions and protein functions. 2-fluorohistidine and 4-fluorohistidine are
fluorinated analogues of histidine, offering valuable tools in biophysical studies with their
altered pKa values compared to the canonical amino acid.
In this dissertation, the molecular properties of 2-fluorohistidine, 4-
fluorohistidine, and analogues are studied with different electronic structure calculations.
Among the two tautomeric states of histidine at neutral pH, it was found that 2-
fluorohistidine prefers the τ-tautomeric state, whereas 4-fluorohistidine exclusively stays
in the π-tautomeric state. While the 1
H signal shifts downfield in both isomers upon ring
protonation, the 19F signal of 2-fluorohistidine also shifts downfield but 19F in 4-
fluorohistidine shifts upfield. The reason for this unusual behavior is explained here. The
effect of different environments (solvation effects, intramolecular hydrogen bonding
effect, backbone effects) on tautomeric stabilities and fluorine chemical shifts are
discussed. This work explains the role of histidine’s C4-H bond as a potential hydrogen
bond donor. The results indicate that the C4-H bonds in histidine and 2-fluorohistidine in
the τ-tautomeric states act as strong hydrogen bond donors.
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Thesis (Ph.D.)-- Wichita State University, College of Liberal Arts and Sciences, Dept. of Chemistry
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Wichita State University
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Copyright 2018 by Chandana Kasireddy
All Rights Reserved