4.6 Article

Average orientation of a fluoroaromatic molecule in lipid bilayers from DFT-informed NMR measurements of 1H-19F dipolar couplings

Journal

PHYSICAL CHEMISTRY CHEMICAL PHYSICS
Volume 20, Issue 27, Pages 18207-18215

Publisher

ROYAL SOC CHEMISTRY
DOI: 10.1039/c8cp01064a

Keywords

-

Funding

  1. British Heart Foundation [PG/16/97/32567]

Ask authors/readers for more resources

Fluorine is often incorporated into the aromatic moieties of synthetic bioactive molecules such as pharmaceuticals and disease diagnostics in order to alter their physicochemical properties. Fluorine substitution may increase a molecule's lipophilicity, thereby enabling its diffusion across cell membranes to enhance bioavailability or to exert a direct physiological effect from within the lipid bilayer. Understanding the structure, dynamics and orientation of fluoroaromatic molecules in lipid bilayers can provide useful insight into the effect of fluorine on their mode of action, and their interactions with membrane-embedded targets or efflux proteins. Here we demonstrate that NMR measurements of F-19 chemical shift anisotropy combined with H-1-F-19 dipolar coupling measurements together report on the average orientation of a lipophilic fluoroaromatic molecule, 4-(6-fluorobenzo[d] thiazol-2-yl) aniline (FBTA), rapidly rotating within a lipid bilayer. The F-19 chemical shift tensor orientation in the molecular frame was calculated by density functional theory and corroborated by H-1-F-19 PISEMA NMR. It was then possible to analyse the line shapes of proton-coupled and proton-decoupled F-19 spectra of FBTA in chain perdeuterated dimyristoylphosphatidylcholine (DMPC-d(54)) bilayers to restrict the average axis of molecular reorientation of FBTA in the bilayer to a limited range orientations. This approach, which exploits the high sensitivity and gyromagnetic ratios of F-19 and H-1, will be useful for comparing the membrane properties of related bioactive fluoroaromatic compounds.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available