Peptide and Protein Conformations in Fluorinated Alcohols and Osmolytes. Addition of fluorinated alcohols or an osmolyte such as trimethylamine N-oxide (TMAO) to aqueous solutions of peptides and proteins often alters the dominant conformation of these biomaterials. Why these effects occur is not always apparent, although at least in some cases it appears that selective interaction with solvent molecules is involved. We are using heteronuclear 1H-{19F} and homonuclear 1H{1H} intermolecular NOE experiments to examine such solvent-solute interactions. Current efforts include development of computational methods for quantitative prediction of the NOEs using solution properties and the conformations of the solute. Experimental work is focused on model systems, peptide hormones, toxins and small proteins. Eventually, we hope to understand the conformations of fibril-forming peptides and proteins produced by these mixtures and how these conformations lead to the formation of the neurofibrillary tangles that characterize diseases such as Alzheimer's, Parkinson's and other degenerative diseases.

Solvation of Organic Molecules in Perfluorinated Solvents. Fluorous phase methods for separations of reactants and products in an organic reaction depend on the ability to modify reacting structures so that they are compatible with the unusual solvating properties of highly fluorinated liquids. NMR studies of solvation in these systems are underway to define solvent-solute interactions and the minimal structural features needed to achieve desired solubility. Studies of small organic molecules in fluorocarbon and hydrocarbon solvents are being used to test the theoretical and experimental methods.

Origins and Predictions of Fluorine Chemical Shifts in Biological Macromolecules. Large, tertiary structure-dependent chemical shift effects are seen when fluorine is incorporated into biological structures. The ability to interpret these effects in terms of structural correlates would be useful in studies of fluorine-containing systems, particularly those involving ligand-macromolecule interactions. Work so far shows that consideration of long-range electrostatic interactions and nearest-neighbor contacts can account for many shifts observed. However, some shifts are not well predicted by any procedure and these situations may signal the presence of unexpected conformational motions. Current work involves computational studies of fluorine shifts in several enzymes.