Dalvit, Claudio and Vulpetti, Anna (2011) Fluorine-Protein Interactions and 19F NMR Isotropic Chemical Shift: An Empirical Correlation. ChemMedChem, 6 (1). pp. 104-114. ISSN 1860-7179

Abstract

An empirical correlation between the fluorine isotropic chemical shift measured in 19F NMR spectroscopy and the type of fluorine-protein interactions observed in the crystal structures is presented. The CF, CF2 and CF3 groups present in fluorinated ligands contained in the Protein Data Bank were classified according to their 19F NMR chemical shift and their close intermolecular contacts with the protein atoms. Shielded fluorines, i.e., with increased electron density, are observed preferentially in close contact to hydrogen bond donors of the protein suggesting the possibility of intermolecular hydrogen bond formation. Deshielded fluorines are found preferentially in close contact with hydrophobic sidechains and with the carbon of the carbonyl of the protein backbone. Correlation of the 19F NMR chemical shift and hydrogen bond distance derived experimentally and computed with quantum chemical methods is also presented. The proposed “rule of shielding” provides some insight and guidelines in the selection of the appropriate fluorinated moiety to be judiciously inserted into the molecule for making the most favorable interactions with the receptor.

Item Type:	Article
Date Deposited:	13 Oct 2015 13:15
Last Modified:	13 Oct 2015 13:15
URI:	https://oak.novartis.com/id/eprint/3644