title: Fluorine bonding enhances the energetics of protein-lipid binding in the gas phase.
abstract: This paper reports on the first experimental study of the energies of noncovalent fluorine bonding in a protein-ligand complex in the absence of solvent. Arrhenius parameters were measured for the dissociation of gaseous deprotonated ions of complexes of bovine β-lactoglobulin (Lg), a model lipid-binding protein, and four fluorinated analogs of stearic acid (SA), which contained (X =) 13, 15, 17, or 21 fluorine atoms. In all cases, the activation energies (E(a)) measured for the loss of neutral XF-SA from the (Lg + XF-SA)⁷⁻ ions are larger than for SA. From the kinetic data, the average contribution of each > CF₂ group to E(a) was found to be ~1.1 kcal mol⁻¹, which is larger than the ~0.8 kcal mol⁻¹ value reported for > CH₂ groups. Based on these results, it is proposed that fluorocarbon–protein interactions are inherently stronger (enthalpically) than the corresponding hydrocarbon interactions.
authors.forename: Lan
authors.initials: L
authors.lastname: Liu
authors.forename: Nobar
authors.initials: N
authors.lastname: Jalili
authors.forename: Alyson
authors.initials: A
authors.lastname: Baergen
authors.forename: Simon
authors.initials: S
authors.lastname: Ng
authors.forename: Justin
authors.initials: J
authors.lastname: Bailey
authors.forename: Ratmir
authors.initials: R
authors.lastname: Derda
authors.forename: John S
authors.initials: JS
authors.lastname: Klassen
mesh_terms: D000818:Animals; D001665:Binding Sites; D002417:Cattle; D004735:Energy Transfer; D054879:Halogenation; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D007782:Lactoglobulins / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D055550:Protein Stability; D021241:Spectrometry, Mass, Electrospray Ionization; D013229:Stearic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D014835:Volatilization
chemical_list: D006845:Hydrocarbons, Fluorinated; D007782:Lactoglobulins; D008024:Ligands; D013229:Stearic Acids