Fluorination fluorous interactions

This chapter aims to summarize our efforts to investigate the effects of fluorinated amino acid substitutes on the interactions with natural protein environments. In addition to a rather specific example concerning the interactions of small peptides with a proteolytic enzyme, we present a simple polypeptide model that aids for a systematic investigation of the interaction pattern of amino acids that differ in side chain length as well as fluorine content within both a hydrophobic and hydrophilic protein environment. Amino acid side chain fluoiination highly affects polypeptide folding due to steric effects, polarization, and fluorous interactions. 

The reason why fluorous alkanes are immiscible with normal alkanes possibly stems from their different conformations -alkanes exist in well-known zig-zag conformations, whereas perfluoro-n-alkanes adopt more helical conformations because of the larger van der Waals radius of fluorine (r = 135 pm) as compared to that of hydrogen (r = 120 pm). Molecules of fluorous solvents are also subject to very weak van der Waals interactions due to the low polarizability of the electrons of the CF2 groups. As a... 

Rule 4 The number of anti-fluorous functional groups capable of attractive in-termolecular interactions, via electrostatic forces, hydrogen bonds, or dispersion interactions must be minimized [16]. An example of such an anti-fluorous effect is the low fluorophilicity of hexafluorobenzene (12) and pentafluorobenzene (13) despite their high relative fluorine content. Both compounds can participate in specific electrostatic interactions with electron-rich hydrocarbons, for example the toluene component of the biphasic test mixture. 

A few solvents exhibit intermediate properties. For example, both BTF (Ref. 22) and F-626 (Ref. 23 see Section 3.1) are able to dissolve appreciable quantities of both fluorous and non-fluorous solutes. Other solvents are often mistakenly assumed to be fluorous. Of these, the most important are perfluoroarenes such as hexafluo-robenzene. The arene tt clouds and sp carbon-fluorine bonds lead to significant intermolecular bond dipoles, induced dipoles and quadrupolar interactions with non-fluorous molecules. ... 

Recently, fluorous chemistry has been used to solubilize and phase-transfer nanocrystals of metals (Au) and chalcogenides (CdS) as well as inorganic nanorods (ZnO) [551]. Here, a fluorous label (e.g. fluorinated alkane thiol) is attached to the nanostructures which are then readily extracted by a fluorocarbon from aquous or hydrocarbon solutions, due to fluorine-fluorine interaction. This method not only enables the purification of the nanostructures, but also helps one to study them in the most-nonpolar medium possible, the refractive index of fluorocarbon being around 1.2. 

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