PROTONATION OF PEPTIDES .2. PROTONATION OF AN AMIDE AND OF A DIAMIDE IN DICHLOROACETIC ACID AND BEHAVIOR OF POLY-GAMMA-BENZYL-L-GLUTAMATE IN DICHLOROACETIC ACID AND IN SOME MIXED SOLVENTS

Ultraviolet absorption measurements were made of anisamide in dichloroacetic acid containing isopropylamine or sulfuric acid. Nmr measurements were made of the diamide N-benzoylglycine--propylamide in dichloroacetic acid-deuteriochloroform mixtures, and in dichloroacetic acid containing added sulfuric acid. It was concluded that neither amide was protonated in dichloroacetic acid solution, and that as a consequence, polypeptides like poly-γ-benzyl-L-glutamate exist in the coil conformation in dichloroacetic acid because of strong solvation rather than protonation. Optical titrations of poly-γ-benzyl-L-glutamate were carried out in mixtures of dichloroacetic acid with a number of cosolvents which brought about coil-to-helix transitions. The order of decreasing efficiency of these cosolvents in effecting the transitions was: triethylamine > acetic acid ≃ methanol > water ≃ nitrobenzene > nitroethane > formic acid > monochloroacetic acid ∼ cyanoacetic acid ∼ 1,2-di-chloroethane > carbon tetrachloride. The hypothesis was made that this order represented the abilities of the various donors to form hydrogen bonds with either dichloroacetic acid monomeric molecules or with the non-hydrogen-bonded terminal carboxyl group of a chain polymer of the solvent. In either event a shift in solvent polymer-dimer-monomer proportions would take place, reducing the concentration of the chain polymer, and reducing the solvation of the peptide groups of the polymer. © 1969, American Chemical Society. All rights reserved.