Aggregates from Perylene Bisimide Oligopeptides as a Test Case for Giant Vibrational Circular Dichroism

Abstract

Vibrational circular dichroism (VCD) spectroscopy has become an excellent tool to study biological nanostructures and biomimetic materials in their functional environment and is thus complementary to otherwise employed diffraction, imaging, and spectroscopy methods. However, it is still difficult to relate the observed exceptionally large VCD signals to specific structural elements. Here, we systematically studied the VCD signatures of structurally well-defined and thoroughly characterized nanofibrils from oligopeptide-substituted perylene bisimides that comprise single parallel β-sheets. These nanofibrils show a giant VCD signal in the absence of β-sheet stacking and a negative VCD couplet despite their right-handed helicity. The giant VCD signal was very sensitive to subtle changes in the molecular structure as well as (13)C-labeling, which caused a strong disruption of the exciton system as confirmed by two-dimensional infrared spectroscopy. Simulations based on the commonly applied transition dipole coupling model qualitatively reproduced the IR spectra but failed to account for the observed giant VCD or the strong isotope effect. Because our model system and isotope labeling imposes stringent structural constraints of the observed spectroscopic features, our results challenge current assumptions regarding the structural parameters determining VCD sign and intensity. The investigated system may, hence, serve as a benchmark for more sophisticated models with better predictive power for the investigation of protein aggregates in biomedical context or novel oligopeptide-based nanomaterials.

Vibrational circular dichroism of a 2,5‐diketopiperazine (DKP) peptide: Evidence for dimer formation in cyclo LL or LD diphenylalanine in the solid state

“…β‐sheets and coils have, for example, different Amide I spectra from that of the α‐helix . VCD is also very sensitive to the aggregation state and allows the characterization of various size entities ranging from dimers to β‐sheets or fibrils formation, as well as self‐assemblies in solution or in the solid state…”

“…[30][31][32][33][34][35][36][37][38][39] β-sheets and coils have, for example, different Amide I spectra from that of the α-helix. 40 VCD is also very sensitive to the aggregation state and allows the characterization of various size entities ranging from dimers 41 to β-sheets or fibrils formation, 42 as well as self-assemblies in solution or in the solid state. 43 Diketopiperazine (DKP) peptides are an important class of dipeptides with applications in pharmacology as HIV antiviral drugs or anticancer therapy.…”

Vibrational circular dichroism as a probe of solid‐state organisation of derivatives of cyclic β‐amino acids: Cis‐ and trans‐2‐aminocyclobutane‐1‐carboxylic acid

“…It should be noted that the intensity enhancement is also observed for the IR absorption in the region of the ν (NH) stretch. This is, however, not reproduced in the calculation as already described by Marty et al in their study of VCD enhancement in perylene bisimide oligopeptides . A very recent calculation of the VCD signal of solid alanine by means of ab initio molecular dynamics (AIMD) and nuclear velocity perturbation theory (NVPT) has explained the enhancement of the VCD signal in terms of supramolecular helical arrangement of the oscillators .…”

“…In contrast with electronic circular dichroism (ECD) signatures, which have been used for structural characterization of helices or strands, VCD has not been applied yet to ACBC‐based peptides, in particular to their solid state. VCD spectra of solid‐state or supramolecular systems, for example, nanofibrils, polymorphic crystals, or foldamers, are scarce. One of the questions raised by the interpretation of VCD spectra in the solid state is the nature of the minimum‐size cell that is necessary for describing the system.…”

“…In other cases, one has to take into account the crystal unit cell itself or a cluster of definite size like a dimer or a tetramer . Still, the intensity enhancement observed in the solid state has to be fully understood …”