Conformations and Mutarotations of Poly(5-methyl-l-proline)

Optically active poly(cis-5-methyl-L-proline) and poly(trans-5-methyl-L-proline) were synthesized from their respective N-carboxy-anhydrides (NCA). Analysis of the i.r., u.v., n.m.r., ORD, and CD spectra of the polymers showed that two different conformations of each polymer exist in the solid and in solution in appropriate solvents. Form I and form II of poly(trans-5-methylL-proline) were found to have the same conformations as the form I and form II of poly-L-proline, respectively. Form B of poly(cis-5-methyl-Lproline) seemed to have a somewhat different conformation from form II of poly-L-prOline. The changes in viscosity during the mutarotations of the two polymers showed that the mutarotation entailed cis—trans isomerization of amide bonds in the polymers. By following the kinetics of the mutarotations it was found that the activation energies for poly(cis-5-methyl-L-proline) was 22 kcal per residue mole, whereas Ea of poly(trans-5-methyl-L-proline) was 33 kcal per residue mole. The excess 10 kcal for the latter polymer was attributed partially to the steric barrier between the methyl group at the trans-5position and the carbonyl group in the polymer. INTRODUCTION The conformation of poly-L-proline (PP) has been studied in some detail by many investigators1. As determined by x-ray diffraction, PP exists in two different conformations in the solid, namely form I,a right-handed helix with all cis-amide bonds, and form TI, a left-handed helix with all transamide bonds2. It was concluded from optical rotatory dispersion (ORD) and circular dichroism (CD) measurements that these ordered structures are largely maintained in solution in appropriate solvents5—'2 The two forms could be interconverted by changing the solvent compositions1. Since neither intraor inter-molecular hydrogen bonding is possible in PP because of the absence of a hydrogen atom on nitrogen, the ordered structures were believed to be maintained by steric factors, van der Waals interactions between non-bonded atoms and dipolar interactions1. It was felt that the introduction of a group in the 5-position of the prolyl ring might affect the steric and van der Waals interactions and thus influence the formation of the helical conformations and the mutarotations of the polymer. Thus, poly(5-methylproline) was synthesized. 5-Methylproline has two geometric isomers—cis and trans—and optical isomers—n and L—of each geometric isomer. We synthesized polymers of the four optical isomers. 33