The Polar Hydrophobicity of Fluorinated Compounds

Biffinger, Justin C.; Kim, Hong Woo; DiMagno, Stephen G.

doi:10.1002/cbic.200300910

Cited by 449 publications

(333 citation statements)

References 69 publications

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“…Fluorinated amino acids have drawn special attention (4-16) because of the unusual solubility properties of fluorinated hydrocarbons. Several independent studies have shown that fluorination of coiled-coil and helix-bundle proteins leads to enhanced stability with respect to thermal or chemical denaturation (6-12), an effect attributed to the hyper-hydrophobic and fluorophilic character of fluorinated amino acid side chains.Although both classes of compounds are hydrophobic, hydrocarbons and fluorocarbons differ in important ways (17)(18)(19)(20)(21)(22). The high electronegativity of fluorine renders the C-F bond both strongly polar and weakly polarizable (17,21,22).…”

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confidence: 99%

“…Although both classes of compounds are hydrophobic, hydrocarbons and fluorocarbons differ in important ways (17)(18)(19)(20)(21)(22). The high electronegativity of fluorine renders the C-F bond both strongly polar and weakly polarizable (17,21,22).…”

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confidence: 99%

“…The high electronegativity of fluorine renders the C-F bond both strongly polar and weakly polarizable (17,21,22). The dipole associated with the C-F bond exerts strong inductive effects on neighboring bonds (23) and can form reasonably strong electrostatic interactions with ionic or polar groups when the two moieties are appropriately positioned.…”

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Hydration dynamics at fluorinated protein surfaces

Kwon

Yoo

Othon

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Water-protein interactions dictate many processes crucial to protein function including folding, dynamics, interactions with other biomolecules, and enzymatic catalysis. Here we examine the effect of surface fluorination on water-protein interactions. Modification of designed coiled-coil proteins by incorporation of 5,5,5-trifluoroleucine or (4S)-2-amino-4-methylhexanoic acid enables systematic examination of the effects of side-chain volume and fluorination on solvation dynamics. Using ultrafast fluorescence spectroscopy, we find that fluorinated side chains exert electrostatic drag on neighboring water molecules, slowing water motion at the protein surface.fluorine | noncanonical amino acids | protein engineering | solvation dynamics | ultrafast hydration T he past decade has witnessed substantial expansion in the number and diversity of noncanonical amino acids that can be incorporated into recombinant proteins expressed in bacterial cells (1-3). Fluorinated amino acids have drawn special attention (4-16) because of the unusual solubility properties of fluorinated hydrocarbons. Several independent studies have shown that fluorination of coiled-coil and helix-bundle proteins leads to enhanced stability with respect to thermal or chemical denaturation (6-12), an effect attributed to the hyper-hydrophobic and fluorophilic character of fluorinated amino acid side chains.Although both classes of compounds are hydrophobic, hydrocarbons and fluorocarbons differ in important ways (17)(18)(19)(20)(21)(22). The high electronegativity of fluorine renders the C-F bond both strongly polar and weakly polarizable (17,21,22). The dipole associated with the C-F bond exerts strong inductive effects on neighboring bonds (23) and can form reasonably strong electrostatic interactions with ionic or polar groups when the two moieties are appropriately positioned. The hydrophobic character of fluorinated compounds has been described as "polar hydrophobicity (17)," and is believed to play important roles in organic and medicinal chemistry. Furthermore, the C-F bond is significantly longer than the C-H bond, and the calculated volume of the trifluoromethyl group is about twice that of a methyl group (20). The studies described here constitute an attempt to understand more fully the interaction of water with fluorinated molecular surfaces, and to provide a sound basis for the use of fluorinated amino acids in the engineering of proteins with unique and useful physical properties.The hydration layer adjacent to protein surfaces exhibits properties different from those of bulk water; the more rigid and denser structure of the hydration layer plays a crucial role in protein structure, folding, dynamics, and function (24-26). Elucidation of the dynamic features of this region, on the time scales of atomic and molecular motion, is essential in understanding protein hydration. In the past decade, the knowledge of hydration on protein surfaces has been extensively expanded by studying the dynamic properties of biological water for various pro...

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Hydration dynamics at fluorinated protein surfaces

Kwon

Yoo

Othon

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…Though C-F bond is highly dipolar due to its large dipole moment, the net dipole moment of CF 3 , CF 2 and CF-CF bonding structures is very small due to geometrical structure. In addition, C-F bond is relatively nonpolarizable so that hydrogen bonding to C-F dipoles is not generally observed in polar solvents like water [46]. Consequently, incorporation of fluorine in carbon network reduced the polar component in the surface energy, which resulted in a hydrophobic surface.…”

Section: X-ray Photoelecron Spectroscopy (Xps) Studiesmentioning

confidence: 99%

Surface energy of the plasma treated Si incorporated diamond-like carbon films

Roy

Choi

Park

et al. 2007

Diamond and Related Materials

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Surface energy and surface chemical bonds of the plasma treated Si incorporated diamond-like carbon films (Si-DLC) were investigated. The Si-DLC films were prepared by r.f. plasma assisted chemical vapor deposition using benzene and diluted silane (SiH 4 /H 2 = 10:90) as the precursor gases. The Si-DLC films were subjected to plasma treatment using various gases like N 2 , O 2 , H 2 and CF 4 . The plasma treated Si-DLC films showed a wide range of water contact angles from 13.4°to 92.1°. The surface energies of the plasma treated Si-DLC films revealed a high polar component for O 2 plasma treated Si-DLC films and a low polar component for CF 4 plasma treated Si-DLC films. The CF 4 plasma treated Si-DLC films indicated the minimum surface energy. X-ray photoelectron spectroscopy (XPS) revealed that the polarizability of the bonds present on the surface explains the hydrophilicity and hydrophobicity of the plasma treated Si-DLC films. We also suggest that the O 2 plasma treated surface can provide an excellent hemocompatible surface from the estimated interfacial energy between the plasma treated Si-DLC surface and human blood.

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“…The presence of a fluorine serves to increase drug lipophilicity [5,6] which is especially important when designing drugs that are intended to cross the blood-brain barrier [7]. Fluorination of drug compounds also affects physical…”

Section: Conclusion 58 Introductionmentioning

confidence: 99%