Solvation of serine-based model peptides and the role of the intramolecular OH·O hydrogen bond in interpreting VCD spectra

Abstract

Infrared and vibrational circular dichroism (VCD) spectra are occasionally very sensitive to solute–solvent interactions and show distinct spectral changes when strong solute–solvent hydrogen bonds give rise to conformational changes. In this regard, small peptides are ideal model systems to investigate such solvent effects on IR and VCD spectra as they possess several hydrogen bonding donor sites. In the present study, we investigate serine and serine-phenylalanine, which both are N-protected with Boc and C-capped with n-propylamine. Compared to previously studied model peptides, the serine residue introduces a strong hydrogen bonding site that competes with the amides for intra- and intermolecular interactions. For both compounds, we computationally found that the intramolecular OH·O interactions are preferentially broken by DMSO, but it was not sufficient to model only this particular interaction. Instead, depending on the conformer family, it was necessary to consider different numbers of solvent molecules in the computed structures and the experimental spectra were found to be best described by assuming mixed solvation states. Our analyses show that the IR and VCD spectra of molecules with multiple hydrogen bonding cannot be simulated by simply solvating all donor sites as this would neglect the presence of important conformer families. In turn, these results stresss the need for novel routines to account for solvation in IR and VCD spectra, that help estimating the contributions of different solvations states to the conformational distribution.