Two-Dimensional Infrared Spectral Signatures of 310- and α-Helical Peptides

Two-dimensional infrared (2D IR) spectra of Cα-alkylated model octapeptides Z-(Aib)8-OtBu, Z-(Aib)5-l-Leu-(Aib)2-OMe, and Z-[l-(αMeVal)]8-OtBu have been measured in the amide I region to acquire 2D spectral signatures characteristic of 310- and α-helical conformations. Phase-adjusted 2D absorptive spectra recorded with parallel polarizations are dominated by intense diagonal peaks, whereas 2D rephasing spectra obtained at the double-crossed polarization configuration reveal cross-peak patterns that are essential for structure determination. In CDCl3, all three peptides are of the 310-helix conformation and exhibit a doublet cross-peak pattern. In 1,1,1,3,3,3-hexafluoroisopropanol, Z-[l-(αMeVal)]8-OtBu undergoes slow acidolysis and 310-to-α-helix transition. In the course of this conformational change, its 2D rephasing spectrum evolves from an elongated doublet, characteristic of a distorted 310-helix, to a multiple-peak pattern, after becoming an α-helix. The linear IR and 2D absorptive spectra are much less informative in discerning the structural changes. The experimental spectra are compared to simulations based on a vibrational exciton Hamiltonian model. The through-bond and through-space vibrational couplings are modeled by ab initio coupling maps and transition dipole interactions. The local amide I frequency is evaluated by a new approach that takes into account the effects of hydrogen-bond geometry and sites. The static diagonal and off-diagonal disorders are introduced into the Hamiltonian through statistical models to account for conformational fluctuations and inhomogeneous broadening. The sensitivity of cross-peak patterns to different helical conformations and the chain length dependence of the spectral features for short 310- and α-helices are discussed.