Stereochemistry-dependent hydrogen bonds stabilise stacked conformations in jet-cooled cyclic dipeptides: (LD) vs. (LL) cyclo tyrosine–tyrosine

Abstract

Tyrosine-containing cyclic dipeptides based on a diketopiperazine (DKP) ring are studied under jet-cooled conditions using resonance-enhanced multi-photon ionisation (REMPI), conformer-selective IR-UV double resonance vibrational spectroscopy and quantum chemical calculations. The conformational landscape of the dipeptide containing natural L tyrosine (Tyr), namely c-LTyr-LTyr strongly differs from that of its diastereomer c-LTyr-DTyr. A similar family of conformers exists in both systems, with one aromatic ring folded on the dipeptide DKP ring and the other one extended. Weak NHπ and CHπ interactions are observed, which are slightly different in c-LTyr-LTyr and c-LTyr-DTyr. These structures are identical to those of LL and LD cyclo diphenylalanine, which only differ from c-Tyr-Tyr by the absence of hydroxyl on the benzene rings. While this is the only conformation observed for c-LTyr-DTyr, c-LTyr-LTyr exhibits an additional form stabilised by the interaction of the two hydroxyls, in which the two aromatic rings are in a stacked geometry. Stereochemical effects are still visible in the radical cation, for which one structure is observed for c-LTyr-DTyr, while the spectrum of the c-LTyr-LTyr radical cation is explained in terms of two co-existing structures.

Conformational Study of the Jet-Cooled Diketopiperazine Peptide Cyclo Tyrosyl-Prolyl

“…These values are close to those for tyrosine, which range from 35491 cm -1 to 35650 cm -1 depending on the conformer [41][42][43][44][45] or to those for cyclo Tyr-Tyr. 12 Several vibronic bands appear in these spectra, suggesting strong vibronic activity and/or coexistence of conformers. The spectrum of c-LL shows four origin-like transitions noted A (35498 cm -1 ), B (35532 cm -1 ), C (35592 cm -1 ), D (35673 cm -1 ) in Figure 4.…”

“…This contrasts to the previous findings on neutral or protonated cyclo PhePhe, or neutral cyclo Ty-Tyr, in which homochirality was always favored. [11][12]14 Among the studied DKP dipeptides, cyclo Tyr-Pro stands out by the cyclic nature of the proline residues, which introduces additional conformational bias. As a result, the NH… interaction,…”

“…A shoulder appears at the low-energy side of the ν(NH) stretch of C and D, possibly due to the presence of an overtone or combination band, as already observed for other DKP dipeptides. 12,14 The most apparent difference between the two diastereomers is that the ν(NH) stretch is shifted up in energy by ~ 30 cm -1 in c-LD relative to c-LL.…”

Near-Ultraviolet Circular Dichroism and Two-Dimensional Spectroscopy of Polypeptides

“…Recent combined theoretical (DFT calculations) and experimental (resonance-enhanced multiphoton ionisation and double resonance infrared ultraviolet) spectroscopic studies have examined jet-cooled cyclic dipeptides in gas phase. BenNasr et al [30] found that the conformational landscape of cyclo(L-Tyr-L-Tyr) strongly differs from that of its diastereomer cyclo(L-Tyr-D-Tyr). The same techniques were employed to study the conformational landscape of cyclo(L-Tyr-L-Pro) and cyclo(L-Tyr-D-Pro) [31], where the simulation of the vibronic pattern of the S 0 -S 1 transition was necessary to assign the observed spectra to either folded or extended conformations.…”

Chirality Effects in Jet-Cooled Cyclic Dipeptides

“…[20] We have undertaken the study of DKP dipeptides in different environments, either in the solid state by vibrational circular dichroism (VCD), protonated in a room-temperature ion trap, or under supersonic expansion conditions). [21][22][23][24][25] The aim of this study is to understand the factors that determine the structural differences between the molecule with residues of natural chirality L and that containing one D residue. This work is part of our recent studies on chirality effects in cyclic systems at low temperature.…”