Competition between inter and intramolecular hydrogen bond evidenced by vibrational circular dichroism spectroscopy: The case of (1S,2R)‐(−)‐cis‐1‐amino‐2‐indanol

Barbu‐Debus, Katia Le; Zehnacker‐Rentien, Anne

doi:10.1002/chir.23362

Cited by 2 publications

(1 citation statement)

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“…Without dispersion corrections, a different conformer of rotaxane dominated and gave a VCD spectrum in good agreement with experiment. 105 Also Merten and coworkers 106−109 and Zehnacker and co-workers 110,111 have shown in several works that including dispersion correction results in significant shifts in the conformational preferences, and that the experimental data are in better agreement with spectra calculated without dispersion corrections. On the basis of these previous observations and our results, it appears that VCD is a sensitive probe of molecular conformation and could hence be used to refine the description of dispersion interactions in quantum-chemical calculations.…”

Section: (Overlap Estimates S)mentioning

confidence: 96%

A Computational Protocol for Vibrational Circular Dichroism Spectra of Cyclic Oligopeptides

2022

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Cyclic peptides are a promising class of compounds for next-generation antibiotics as they may provide new ways of limiting antibiotic resistance development. Although their cyclic structure will introduce some rigidity, their conformational space is large and they usually have multiple chiral centers that give rise to a wide range of possible stereoisomers. Chiroptical spectroscopies such as vibrational circular dichroism (VCD) are used to assign stereochemistry and discriminate enantiomers of chiral molecules, often in combination with electronic structure methods. The reliable determination of the absolute configuration of cyclic peptides will require robust computational methods than can identify all significant conformers and their relative population and reliably assign their stereochemistry from their chiroptical spectra by comparison with ab initio calculated spectra. We here present a computational protocol for the accurate calculation of the VCD spectra of a series of flexible cyclic oligopeptides. The protocol builds on the Conformer-Rotamer Ensemble Sampling Tool (CREST) developed by Grimme and co-workers ( 32073075 Phys. Chem. Chem. Phys. 2020 22 7169 7192 and 30943025 J. Chem. Theory. Comput. 2019 15 2847 2862 ) in combination with postoptimizations using B3LYP and moderately sized basis sets. Our recommended computational protocol for the computation of VCD spectra of cyclic oligopeptides consists of three steps: (1) conformational sampling with CREST and tight-binding density functional theory (xTB); (2) energy ranking based on single-point energy calculations as well as geometry optimization and VCD calculations of conformers that are within 2.5 kcal/mol of the most stable conformer using B3LYP/6-31+G*/CPCM; and (3) VCD spectra generation based on Boltzmann weighting with Gibbs free energies. Our protocol provides a feasible basis for generating VCD spectra also for larger cyclic peptides of biological/pharmaceutical interest and can thus be used to investigate promising compounds for next-generation antibiotics.

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Section: (Overlap Estimates S)mentioning

confidence: 96%