Interactions of aggregating peptides probed by IR-UV action spectroscopy.

Peptide aggregation, the self-assembly of peptides into structured beta-sheet fibril structures, is driven by a combination of intra- and intermolecular interactions. Here, the interplay between intramolecular and formed inter-sheet hydrogen bonds and the effect of dispersion interactions on the formation of neutral, isolated, peptide dimers is studied using infrared action spectroscopy. Therefore, four different homo- and heterogenous dimers resulting from three different alanine-based model peptides have been formed under controlled and isolated conditions. The peptides differ from one another by the presence and location of a UV chromophore containing end cap. The conformations of the monomers of the peptides direct the final dimer structure: strongly bonded or folded structures result in weakly bound dimers. Here, intramolecular hydrogen bonds are favored over new intermolecular hydrogen bond interactions. In contrast, linear monomers are the ideal template to form parallel beta-sheet type structures. The weak intramolecular hydrogen bonds present in the linear monomers are replaced by the stronger inter-sheet hydrogen bond interactions. The influence of π-π dispersion interactions on the structure of the dimers is minimal, and the phenyl rings have a tendency to fold away from the peptide backbone to favour intermolecular hydrogen bond interactions over dispersion interactions. Quantum chemical calculations confirm our experimental observations.

Conformational assignment of gas phase peptides and their H-bonded complexes using far-IR/THz: IR-UV ion dip experiment, DFT-MD spectroscopy, and graph theory for mode assignment.

The combined approach of gas phase IR-UV ion dip spectroscopy experiments and DFT-based molecular dynamics simulations for theoretical spectroscopy reveals the 3D structures of (Ac-Phe-OMe)1,2 peptides using their far-IR/THz signatures. Both experimental and simulated IR spectra are well-resolved in the 100-800 cm-1 domain, allowing an unambiguous assignment of the conformers, that could not be achieved in other more congested spectral domains. We also present and make proofs-of-principles for our newly developed theoretical method for the assignment of (anharmonic) vibrational modes from MD simulations based on graph theory coupled to APT-weighted internal coordinates velocities DOS spectra. The principles of the method are reviewed, applications to the simple gas phase water and NMA (N-methyl-acetamide) molecules are presented, and application to the more complex (Ac-Phe-OMe)1,2 peptidic systems shows that the complexity in assigning vibrational modes from MD simulations is reduced with the graphs. Our newly developed graph-based methodology is furthermore shown to allow an easy comparison between the vibrational modes of isolated monomer(s) and their complexes, as illustrated by the (Ac-Phe-OMe)1,2 peptides.

Fingerprints of inter- and intramolecular hydrogen bonding in saligenin-water clusters revealed by mid- and far-infrared spectroscopy.

Saligenin (2-(hydroxymethyl)phenol) exhibits both strong and weak intramolecular electrostatic interactions. The bonds that result from these interactions compete with intermolecular hydrogen bonds once saligenin binds to one or more water molecules. Infrared (IR) ultraviolet (UV) ion-dip spectroscopy was used to study isolated saligenin-(H2O)n clusters (n = 1-3) in the far- and mid-IR regions of the spectrum. Both harmonic and anharmonic (coupled local modes and Born-Oppenheimer molecular dynamics) quantum chemical calculations were applied to assign cluster geometries to the measured spectra, and to assign vibrational modes to all spectral features measured for each cluster. The hydrated clusters with n = 1 and 2 have geometries that are quite similar to benzyl alcohol-water clusters, whereas the larger clusters with n = 3 show structures equivalent to the isolated water pentamer. Systematic shifts in the frequencies of three hydrogen bond (H-bond) deforming modes, namely OH stretching, OH torsion and H-bond stretching, were studied as a function of the hydrogen bond strength represented by either the OH bond length or the H-bond length. The shifts of the frequencies of these three modes correlate linearly to the OH length, despite both intra- and intermolecular H-bonds being included in this analysis. The OH torsion vibration displays the largest frequency shift when H-bonded, followed by the OH stretching vibrations and finally the H-bond stretching frequency. The frequency shifts of these H-bond deforming modes behave non-linearly as a function of the H-bond length, asymptotically approaching the frequency expected for the non H-bonded modes. The nonlinear behavior was quantified using exponential functions.

Mapping gas phase dipeptide motions in the far-infrared and terahertz domain.

Vibrational signatures of Ac-Phe-AA-NH2 dipeptides are recorded and analysed in the far IR/THz spectral domain (100-800 cm-1, 3-24 THz), with the 'AA' amino acid chosen within the series 'AA' = Gly, Ala, Pro, Cys, Ser, Val. Phe stands for phenylalanine. IR-UV ion dip experiments are conducted on the free electron laser FELIX and combined with DFT-based molecular dynamics simulations for the calculation of the dynamical anharmonic vibrational spectra. The excellent agreements between the experimental and theoretical spectra of the Ac-Phe-AA-NH2 series allow us to make detailed and unambiguous mapping of the vibrational motions into three main domains: 700-800 cm-1 for C-H waggings, 400-700 cm-1 for N-H waggings, with a one-to-one signature per amide N-H backbone group, 0-400 cm-1 for delocalized and large amplitude collective motions over the dipeptide backbone, with backbone torsional motions arising <100 cm-1.

N-Substituted Azacalixphyrins: Synthesis, Properties, and Self-Assembly.

Pre- and postintroduction of substituents with respect to the macrocyclization step leads to previously unknown N-substituted azacalixphyrins. The stepwise synthetic approach has been studied in detail to highlight the key role of the N-substituents of the precursors and/or intermediates in terms of reactivity. Based on a combined experimental and theoretical investigation, the relationship between the properties of the macrocycles and their degree of substitution is rationalized. Depending on the nature of the N-substituents, the formation of supramolecular ribbon-like structures could also be observed, as demonstrated by combined TEM, SEM, AFM, and FTIR experiments.

Can far-IR action spectroscopy combined with BOMD simulations be conformation selective?

The combination of conformation selective far-IR/UV double resonance spectroscopy with Born-Oppenheimer molecular dynamics (BOMD) simulations is presented here for the structural characterization of the Ac-Phe-Pro-NH2 peptide in the far-infrared spectral domain, i.e. for radiation below 800 cm(-1). Two conformers have been shown to be present in the experiment, namely a conformer with a γ-turn fold (C7 interaction) and a ß-turn fold (C10 interaction). The combined experimental and theoretical work presented here aims to provide spectral features typical of each conformer in this far-IR domain. The simulated BOMD far-IR spectra agree well with the experimental spectra and allow direct assignment of the observed bands. These assignments show that the 400-550 cm(-1) spectral domain is conformer selective, allowing us to distinguish the H-bond signature of the γ-turn from the ß-turn.