A VCD study on micro-solvation and self-aggregation of N-acetyl tryptophan propylamide

The analysis of VCD spectra recorded in hydrogen bonding solvents often requires the explicit consideration of solute-solvent interactions in the DFT-based spectral calculations. While such a micro-solvation approach is straightforward for molecules with a single hydrogen bonding site, the possibility of finding the solute in various solvation states further complicates the analysis for molecules with several donor sites. Herein we analyse the VCD and IR spectra of the small peptide Ace-Trp-N(n-Pr), which were recorded in chloroform-d₁, acetonitrile-d₃ and dimethylsulfoxide-d₆, and aim to evaluate how molecular dynamics simulations can support a micro-solvation approach by providing information on the number of simultaneous solute-solvent interactions. The spectra recorded in DMSO-d₆ and ACN-d₃ are well described in the micro-solvation scheme as a mixture of double- and triple-solvated species, and the corresponding MD simulations are found to confirm the derived conformational preferences. Unexpectedly, we found that the results of the analysis of the experimental spectra taken in CDCl₃ are not well reproduced by those computed for the monomeric species. In fact, unlike for previously investigated peptides, dimerization has to be considered. The ratio of monomeric and dimeric species could be derived from MD simulations, which also suggested that the most abundant species is an open-chain dimer with indol-N-H⋯OC_acetyl interactions.