Location of proline derivatives in conformational space. I. Conformational calculations; optical activity and NMR experiments

In order to develop methods of analysis applicable to the determination of the conformation of biological polymers in solution, a series of proline derivatives was studied. The steric constraints of the pyrrolidine ring limit these compounds to a relatively small set of conformations. This set was further reduced by eliminating conformations with large computed conformational energy. Computations revealed that the conformational energy of the proline derivatives fits into one of three classes, depending on the bulk and the polarity of the C‐terminal group. Three analogous classes of optical activity were observed. The optical activity data were analyzed in terms of conformations computed to be of low energy. In some cases qualitative theoretical considerations enabled molecular groups to be located. For example, solvent‐dependent isomerization of the carboxyl hydrogen of N‐acetyl‐L‐proline was detected. Nuclear magnetic resonance provided an experimental measure of the fraction of molecules which had cis unsymmetrically‐substituted tertiary amide groups. This information aided and confirmed the other measures of molecular conformation.