Absolute Configuration of a Cyclic Dipeptide Reflected in Vibrational Optical Activity: Ab Initio and Experimental Investigation

Abstract

The ability of Raman optical activity (ROA) and vibrational circular dichroism (VCD) experiments to determine the absolute configuration of chiral molecules with multiple stereogenic centers was explored for four diastereoisomers of a conformationally flexible cyclic dipeptide, cyclo(Arg-Tyr(OMe)). The reliability of the interpretation depended on the correct description of the molecular conformation, which was found to be strongly affected by intramolecular interactions. In particular, when dispersion corrections were included in the density functional theory calculations, the simulated spectra matched the experimental observations well. Experimental and theoretical ROA and VCD spectra were well correlated for all the absolute configurations (RS, SR, SS, and RR) of protonated cyclo(Arg-Tyr(OMe)). These spectroscopies thus appear useful not only for reliable determination of the absolute configuration and conformation but also in revealing the role of hydrogen bonds and C-H···π interactions in the structure stabilization, which can potentially be used when designing enzyme inhibitors and supramolecular architectures.

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

“…This structure corresponds to NCCC dihedral angles of −58° for the extended Phe and 65° for the folded one. The second subunit is much more symmetrical with Phe substituents located on the same side of the DKP ring, as often observed when the two residues interact with each other . The corresponding dihedral angles are 73° and 59°, respectively.…”

“…The second subunit is much more symmetrical with Phe substituents located on the same side of the DKP ring, as often observed when the two residues interact with each other. 78 The corresponding dihedral angles are 73°and 59°, respectively. Such a structure allows Phe-Phe stacking interaction to take place, similar to what is observed in cyclo LArg-LTrp.…”

Where does the Raman optical activity of [Rh(en)3]3+ come from? Insight from a combined experimental and theoretical approach

“…32,33 The calculations were performed with the B3LYP hybrid exchange-correlation functional [34][35][36] because of its good performance for ROA calculations 25,26,[37][38][39][40] . In order to have a good description of the dispersion interactions, we employed the D2 dispersion correction of Grimme.…”

Three Types of Induced Tryptophan Optical Activity Compared in Model Dipeptides: Theory and Experiment

“…[41,42] Especially, the vibrational methods provide new insight into details of peptide secondary structure. [52][53][54][55][56] This is true also for the Trp-containing dipeptides, although the benefit of the correction within a simplified solvent model may be limited. [49][50][51] As indicated in previous studies the dispersion should be added to most DFT biomolecular studies.…”