Unusual cis-trans isomerism in N-acetyl, N'-methylamide derivatives of syn- and anti-5-methylproline.
By means of carbon-13 n.m.r. spectroscopy, we have investigated cis-trans isomerism for N-acetyl, N'-methylamide derivatives of syn- and anti-5-methylproline (syn: the methyl group and carboxamide are on the same side of the proline ring, anti: on opposite sides). For Ac-syn-5-MeProNHMe, we observe about 25% cis peptide bond isomers in most solvents as is common for oligopeptides of proline. The percentage of cis isomer is about 20% greater for Ac-anti-5-MeProNHMe in non-polar solvents. These percentages show little temperature dependence. The free energy barrier for trans to cis isomerization is 19.4 kcal/mol in dioxane and 20.0 kcal/mol in dimethylsulfoxide for Ac-anti-5-MeProNHMe, in agreement with values observed for other peptides. However, value observed for Ac-syn-5-MeProNHMe are about 2 kcal/mol lower. For the latter peptide the barrier is 1.7 kcal/mol higher in water than in three organic solvents. These results indicate that steric interactions of the 5-methyl group destabilized the trans peptide isomer in Ac-anti-5-MeProNHMe without affecting the isomerization barrier. In contrast, for Ac-syn-5-MeProNHMe, the cis and trans peptide isomers are destabilized by the same amount so that the barrier is lowered without altering the equilibrium ratio. The higher energy barrier in water indicates binding of solvent to the plant peptide ground state.
D006909:Hydroxyproline / Q000031:analogs & derivatives*; D007202:Indicators and Reagents; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D013816:Thermodynamics
D007202:Indicators and Reagents; D006909:Hydroxyproline