Solvent Interactions in Some Conformation-Regulating Solvents for Polypeptides and Proteins

Conductivities, dielectric constants, and infrared spectra have been studied for binary mixtures of anhydrous formic acid with acetonitrile, dioxane, ethylene dichloride, formamide, N-methylformamide, N,N dimethylformamide, acetamide, N-methylacetamide, N,N-dimethylacetamide, and dimethyl sulfoxide. All of these mixtures can act in regulating polypeptide conformation. There is a very marked conductance maximum at 80% formic acid (by volume) in each of the highly protic diluents. There is no evidence of amide group protonation in any of the infrared spectra. Spectral shifts corresponding to hydrogen bonding interactions predominate. The extent of hydrogen bonding between acid and the amide or dimethyl sulfoxide appears to be directly related to the basicity of the carbonyl or sulfoxyl group. The methyl substitution on the carbonyl has a large effect whereas substitution on the amide N has a lesser effect. Hydrogen bonds form between the amide or sulfoxyl oxygen and the hydroxyl group of the acid. These data imply that anhydrous formic acid is a differentiating solvent for amides, in contrast to the stronger acids, trifluoroacetic and dichloroacetic, which have a leveling effect. The formic acidamide systems may thus be useful in probing for differences in peptide bond helix forming ability in proteins and polypeptides.