Do Stereochemical Effects Overcome a Charge-Induced Perturbation in Isolated Protonated Cyclo(Tyr-Tyr)?

Abstract

Two diastereomers of the protonated diketopiperazine (DKP) dipeptide cyclo(Tyr-Tyr), namely, cyclo(LTyr-LTyr)H + and cyclo(LTyr-DTyr)H + , are studied in a cryogenic ion trap by means of IR photodissociation spectroscopy combined with quantum chemical calculations. The two diastereomers have similar structures in which one of the rings is folded over the DKP ring and the other one is extended in a trans geometry, allowing a strong OH + •••π interaction to take place. This contrasts to the observation of a stacked geometry for neutral cyclo(LTyr-LTyr) only under supersonic expansion conditions that do not exist for cyclo(LTyr-DTyr). In the protonated form, the strength of the OH + •••π interaction is different for the two diastereomers, resulting in a ∼110 cm −1 difference in the ν(OH + ) frequency and a smaller but clearly identifiable difference in the protonated amide ν(NH) frequency. Stereochemical effects are therefore still evidenced despite the strong perturbation due to the excess charge.

Does Chiral Sensitivity of a Structure Depend on the Metal Core? Alkali Ion Complexes of Cyclo(Tyr‐Tyr)

“…The geometry of the Li + , Na + and K + ion core complexes were optimised at the B3LYP/6-311 + + G(d,p) level, including the D3 dispersion corrections, [27][28][29] as done previously for the neutral and protonated molecules. [7,17] The LANL2DZ pseudo potential was used for Rb + and Cs + , keeping the 6-311 + + g(d,p) basis set for the C, N, O and H atoms. The harmonic frequencies were calculated at the same level of theory.…”

“…We have undertaken a study of DKP dipeptides containing at least one aromatic amino acid under jet-cooled or ion trap conditions. [7][8][9][10][11][12][13][14][15][16] Among the studied systems, those containing two aromatic amino-acids are of special interest as they raise the question of the localisation of the electronic transition and the coupling between the two aromatic chromophores (see Figure 1). The most stable structures of neutral bi-chromophore DKP dipeptides, like cyclo(phenylalanyl-phenylalanyl) (c-Phe-Phe) or cyclo(phenylalanyl-tyrosyl) (c-Phe-Tyr), [10,14,15] are very similar, although spectroscopically discernible, whether the two residues have identical or opposite absolute configurations.…”

“…Despite the perturbation brought by the point charge and the dominant OH + …π interaction, the two diastereomers are still clearly distinguishable by their spectroscopic signature in the 3 μm region. [7] The study of ion-core complexes of DKP peptides with alkali metals is still scarce. [18] Due to the cyclic nature of the DKP dipeptides, no charge-solvated structure can be formed, in contrast to linear peptides.…”

“…From the fundamental point of view, they provide model systems for studying the influence of the chirality of the residues on the structure of sterically constrained systems. We have undertaken a study of DKP dipeptides containing at least one aromatic amino acid under jet‐cooled or ion trap conditions [7–16] . Among the studied systems, those containing two aromatic amino‐acids are of special interest as they raise the question of the localisation of the electronic transition and the coupling between the two aromatic chromophores (see Figure 1).…”

“…Protonation of the molecule happens on the amide CO and destabilises the stacked geometry to the benefit of a folded‐extended structure stabilised by the interaction between the OH + group and the extended ring, shown in Figures 1e and 1f. Despite the perturbation brought by the point charge and the dominant OH + …π interaction, the two diastereomers are still clearly distinguishable by their spectroscopic signature in the 3 μm region [7] . The study of ion‐core complexes of DKP peptides with alkali metals is still scarce [18] .…”