Hydrogen Bond Acceptor Propensity of Different Fluorine Atom Types: An Analysis of Experimentally and Computationally Derived Parameters

Abstract

The propensity of organic fluorine acting as a weak hydrogen bond acceptor (HBA) in intermolecular and intramolecular interactions has been the subject of many experimental and theoretical studies often reaching different conclusions. Over the last few years, new and stronger evidences have emerged for the direct involvement of fluorine in weak hydrogen bond (HB) formation. However, not all the fluorine atom types can act as weak HBA. In this work, the differential HBA propensity of various types of fluorine atoms was analyzed with a particular emphasis for the different types of alkyl fluorides. This was carried out by evaluating ab initio computed parameters, experimental 19F NMR chemical shifts and small molecule crystallographic structures (extracted from the CSD database). According to this analysis, shielded (with reference to the 19F NMR chemical shift) alkyl mono‐fluorinated motifs display the highest HBA propensity in agreement with solution studies. Although much weaker than other well‐characterized HB complexes, the fragile HBs formed by these fluorinated motifs have important implications for the chemical‐physical and structural properties of the molecules, chemical reactions, and protein–ligand recognition.

Defect Healing in FAPb(I1‐xBrx)3 Perovskites: Multifunctional Fluorinated Sulfonate Surfactant Anchoring Enables >21% Modules with Improved Operation Stability

“…In addition, the improvement in the stability could also be attributed to strong hydrogen bonding (FH) and chelating (formation of chelates between FPb and SOPb) effects. [ 68,70–72 ]…”

“…In addition, the improvement in the stability could also be attributed to strong hydrogen bonding (FH) and chelating (formation of chelates between FPb and SOPb) effects. [68,[70][71][72] We calculated the work function, valence band maximum (VBM), and conduction band minimum (CBM) levels for the pristine and HFSTT-modified perovskite films using the ultraviolet photoelectron spectroscopy (UPS, Figure 4a,b) technique to understand the reason behind the increase in the V oc values of the solar cells. Figure 4c presents the energy level diagrams generated based on the data obtained using the UPS and optical absorption techniques.…”

Deciphering the Flupyrimin Binding Surface on the Insect Nicotinic Acetylcholine Receptor

“…Accordingly, the insect β subunit plays a decisive role in the recognition of the C­(O)­CF 3 pharmacophore. A fragile H-bond between a fluorine atom and the partnering H-donating amino acid has an important implication for protein-ligand recognition. , Although the organic fluorine atom interacts with a cation such as Na + or K + , a CF 3 fluorine contacts Lys ammonium H or Arg guanidinium H . Further, FLP is acaricidal against various ticks (Table S1), while neonicotinoid IMI is less effective, , which is apparently associated with the fact that the FLP C­(O)­CF 3 moiety interacts with the partnering residue(s) on the tick nAChR β subunit.…”

Intermolecular Interactions of Organic Fluorine Seen in Perspective

“…This seems reasonable as we inferred earlier that F_ali and F_phe tend to be more electron rich than the others, which should make the F δ-•••C δ+ interaction stronger. On the other hand, an analysis of 19 F chemical shifts suggested that shielded (high electron density) fluorine atoms in proteins are more likely to interact with hydrogen-bond donors and less likely to form F•••CO interactions than deshielded atoms. 130 The authors argued (along with Holl et al 131 ) that if a fluorine atom with high electron density forms an F•••CO contact it will also form a secondary, and repulsive, interaction to the carbonyl oxygen.…”