Amide I vibrational frequencies of alpha-helical peptides based upon ONIOM and density functional theory (DFT) studies.

We present ONIOM and pure DFT calculations on infrared spectra of alpha-helical-capped polyalanines. The calculations used two-layer ONIOM (B3LYP/D95**:AM1) calculations of the amide I vibrational frequencies for acetyl(ala)NNH2 (N=8, 10, 12-18) whose structures have been previously completely optimized by the same method. These are the first such calculations based upon structures of alpha-helical peptides that are completely optimized using DFT or molecular orbital methods. As the peptide becomes longer, the amide I band becomes both more intense and more red shifted. However, the individual absorptions that contribute most to the band vary between three patterns: one very intense absorption, two absorptions of similar intensity, and two strong absorptions where one is roughly twice as intense as the other. This pattern appears to be related to the relative number of H bonds in the individual H-bonding chains; however, there is one exception. Using 14C=O's to selectively decouple specific C=O's, we found that the couplings between the C=O's within each of the three individual H-bonding chains within the helices follow the same pattern previously reported for planar H-bonding chains of formamides. The coupling between the H-bonding chains appears to involve through-space coupling between the H-bonding chains. While decoupling individual C=O's always decreases the intensity of the amide I band, it leads to complex changes in the individual amide I absorptions that contribute to the band. Depending upon the position of the 14C=O, the amide I band can either red or blue shift. Moreover, the individual absorptions that contribute to the band can increase or decrease in intensity as well as shift. The patterns of the individual absorptions (mentioned above) also change. Using the C=O stretch of acetamide as a reference, we calculate the red shifts for the most intense absorptions to be much greater than predicted by the transition dipole method.