Fluorination conformational changes

Protein Theories. The direct interaction of inhalation anesthetics and proteins has been proposed as the cause of anesthesia. An inhalation agent, whether a noble gas or a fluorinated ether, could dissolve asymmetrically in a protein, Resultant conformational changes in the protein, if these changes occur, could then cause changes in biological activity. 

The use of 19F NMR for a variable temperature (VT) NMR study of fluorinated taxoids is obviously advantageous over the use of H NMR because of the wide dispersion of the l9F chemical shifts that allows fast dynamic processes to be frozen out. Accordingly, F2-paclitaxel 65 and F-docetaxel 66 were selected as probes for the study of the solution structures and dynamic behavior of paclitaxel and docetaxel, respectively, in protic and aprotic solvent systems.77 The inactive 2, 10-diacetyldocetaxel (73) was also prepared to investigate the role of the 2 -hydroxyl moiety in the conformational dynamics.89 While molecular modeling and NMR analyses (at room temperature) of 73 indicate that there is no significant conformational changes as compared to paclitaxel, the 19F NMR VT study clearly indicates that this modification exerts marked effects on the dynamic behavior of the molecule.77... 

As might be anticipated, the majority of solvent effects of the structures of pyridines relate to conformational changes and, where appropriate, this has been mentioned above. It may be further exemplified by the conformational changes observed on addition of alcohols and fluorinated alcohols to solutions of the pyridinium salts such as 51 in water <2000JA738>. Helical coils are favored by the fluorinated alcohols as the co-solvent destabilizes the exposed hydrophobic side chains in other conformations along with favoring the helical conformation entropically. The former effect is less marked in nonfluorinated alcohols. 

Berkessel A, Adrio JA, Ffiittenhain D, Neudorfl JM (2006) Unveiling the booster effect of fluorinated alcohol solvents aggregation-induced conformational changes and cooperatively enhanced Fl-bonding. J Am Chem Soc 128 8421-8426... 

Chemical synthesis has provided an additional route to peptides containing halogenat-ed amino acids. Early 19F-NMR studies of proteins were performed on semi-synthetic polypeptides prepared by attachment of fluorinated probes to the polypeptide. For example, Heustis and Raftery modified ribonuclease by trifluoroacetylation of Lys residues 1 and 7. They then used 19F-NMR to study conformational changes brought about by the presence of inhibitors200. In his review, Gerig provides several other examples of this strategy187. 

Berkessel A, Adrio JA (2004) Kinetic studies of olefin epoxidation with hydrogen peroxide in l,l,l,3,3,3-hexafluoro-2-propanol reveal a crucial catalytic role for solvent clusters. Adv Synth Catal 346 275-280 Berkessel A, Adrio JA (2006) Dramatic acceleration of olefin epoxidation in fluorinated alcohols activation of hydrogen peroxide by multiple H-bond networks. J Am Chem Soc 128 13412-13420 Berkessel A, Adrio JA, Huttenhain D, Neudorfl JM (2006a) Unveiling the booster effect of fluorinated alcohol solvents aggregation-induced conformational changes, and cooperatively enhanced H-bonding. J Am Chem Soc 128 8421-8426... 

Finally, from the NMR spectra of our deoxyfluoro ligands, it has become clear that there is no evidence for any conformational change due to the introduction of fluorine into these molecules (cf. ref. 37 and papers cited therein). 

Piezoelectric materials have, in their structure, dipoles that can be aligned when an electric field is applied in response, dimensional changes occur. The best performance has been obtained with poly(vinylidene fluoride) (PVDF) and derivative. Fluorine on the backbones makes the polymer highly polar and allows reversible conformational change. For PVDF only the beta phase is polar and useful to produce the piezoelectric effect. 

---