Dalvit, Claudio and Vulpetti, Anna (2016) Weak intermolecular hydrogen-bonds with fluorine: detection and implications for enzymatic/chemical reactions, for chemical physical properties and for ligand/protein fluorine NMR screening. Chemistry-a European Journal.

Abstract

It is well known that strong hydrogen bonding interactions play an important role in many chemical and biological systems. However, weak or very weak hydrogen bonds, often difficult to detect and characterize, can also be relevant in many recognition and reactive processes. Fluorine, as hydrogen bond acceptor, has been the subject of many controversial discussions and there are different opinions about it. Recently, it appears that there is compelling experimental evidence for the involvement of fluorine in weak intramolecular or intermolecular hydrogen bonds. Using established NMR methods, we have characterized and measured the strength of intermolecular hydrogen bond complexes involving the fluorine moieties CH2F, CHF2 and CF3 and compared to the well-known hydrogen bond complex formed between acetophenone and the strong hydrogen bond donor p-fluorophenol. We now report evidence of formation of hydrogen bond involving fluorine with significantly weaker donors i.e. 5-fluoroindole and water. A simple NMR method is proposed for the simultaneous measurement of the strength of hydrogen bond formation of an acceptor with a donor and with water. Important implications of these results for enzymatic/chemical reactions involving fluorine, for chemical physical properties and ligand/protein 19F NMR screening are analyzed with experiments and theoretical simulations.

Item Type:	Article
Keywords:	Fluorine, Hydrogen Bond, Fluorine NMR spectroscopy, Fluorine NMR screening, Molecular Matched Pairs Analysis
Date Deposited:	26 Apr 2016 23:45
Last Modified:	26 Apr 2016 23:45
URI:	https://oak.novartis.com/id/eprint/28164