Vibrational and electronic couplings in ultraviolet resonance Raman spectra of cyclic peptides

Abstract

Ultraviolet resonance Raman (UVRR) spectra are reported for a series of cyclic amides. 2-Azacyclotridecone, which has a 13-membered ring, shows a classic trans-amide UVRR spectral pattern, with comparable enhancement of the amide modes II, III and S. When the ring is diminished to eight (ε-caprolactam) or seven (2-azacyclooctanone) members, this pattern is replaced by a single strong band near 1497 cm −1, characteristic of the CN stretch of a cis-amide vibration (amide IIc). Further shrinkage of the ring decreases the amide IIc frequency. It is lowered over 100 cm −1 to 1389 cm −1 in the case of a 4-membered ring (2-azaidine), reflecting diminution of the CN bond order due to ring strain and pyramidalization of the C and N atoms. At the same time the amide Ic (CO stretching) frequency increases, reflecting the localization of the CO double bond. Also the sensitivity to hydrogen–deuterium exchange reverses for amide Ic and IIc modes as ring size decreases. The UV absorption maximum, which is red-shifted for cis-relative to trans-amides, shifts increasingly to the blue as the ring size decreases, again reflecting localization of the π bonding. In the case of amides with 5- and 6-membered rings (2-pyrrolidinone and δ-vareloctam) multiple UVRR bands are seen in the amide IIc region, whose relative intensities are temperature-dependent. These are assigned to conformers in which different members of the ring are out of the mean plane, resulting in variable perturbations of the amide bond. The cyclic dipeptides cyclo(Gly–Gly) and cyclo(Gly–Pro) have perturbed amide IIc frequencies, reflecting the kinematic mixing of the amide coordinates into in- and out-of-phase modes. Excitation profiles reveal electronic mixing as well, with the transition dipoles adding for the in-phase and canceling for the out-of-phase modes.