Conformations of cyclo(L‐alanyl‐L‐alanyl‐ε‐aminocaproyl) and of cyclo(L‐alany1‐D‐alanyl‐ε‐aminocaproyl); cyclized dipeptide models for specific types of β‐bends

Abstract

Conformational energy calculations indicate that the peptide backbones of the low‐energy conformations of the cyclized dipeptide derivatives cyclo (L‐alanyl‐L‐alanyl‐ε‐aminocaproyl) and cyclo (L‐alanyl‐D‐alanyl‐ε‐aminocaproyl) are constrained to form β‐bends of types I + III and II, respectively. Thus, the two compounds can serve as models for the spectroscopic properties of β‐bends of these types. The coupling constants obtained from ¹H n.m.r. spectra in DMSO‐d₆ are consistent with the dihedral angles of the computed lowest‐energy conformations. Differences in ¹³C chemical shifts between the two compounds can be correlated with differences in shielding by C=O groups in bends of various types. ¹H and ¹³C chemical shifts suggest association of cyclo (L‐Ala‐L‐Ala‐Aca) but not of cyclo (L‐Ala‐D‐Ala‐Aca) in dimethylsulfoxide. The different tendencies to associate can be explained in terms of the difference in conformation. The circular dichroism spectra of the two compounds are quite different. In methanol, trifluoroethanol and water, the L‐Ala‐L‐Ala derivative has a positive extremum near 190 nm and two negative extrema near 206 and 220 nm, whereas the L‐Ala‐D‐Ala derivative has a positive extremum at about 203 nm and negative extrema at about 187 and 229 nm. The spectra can be used to estimate the contribution of various bend types in a related series of compounds. A normal mode analysis of the vibrations of the computed low‐energy conformations was compared with solid state infrared and Raman spectra, in order to determine the predominant conformations. The bend types determined by this comparison fully agree with the predictions of the theoretical computations for both derivatives.