VCD spectroscopy reveals that a water molecule determines the conformation of azithromycin in solution

Valverde

2021

Rev. Bras. Farmacogn.

The determination of the absolute configuration of chiral bioactive natural products is a crucial step in their structural characterization. Several well-established techniques, such as X-ray crystallography, stereo-controlled organic synthesis, NMR, and chiroptical spectroscopy, are commonly used to this end. However, even today, the configurational analysis of natural products remains a challenge, with a significant number of reassignments being reported every year. Among chiroptical methods, vibrational circular dichroism (VCD) has emerged as an excellent tool for the assignment of the absolute configuration of structurally diverse chiral natural products directly in solution. This review covers the use of VCD spectroscopy to elucidate the absolute stereochemistry of natural products in Brazil over the last 20 years. Although the number of VCD investigations on secondary metabolites has increased, VCD can still be considered under-explored in Brazil. Therefore, herein, we aim to demonstrate the unparalleled stereochemical discriminatory power of VCD to assign both conformation and absolute configuration of natural products in conditions not commonly accessible to other techniques.

Section: Applications Of Vcd In Brazilmentioning

confidence: 95%

Section: Applications Of Vcd In Brazilmentioning

confidence: 99%

Vibrational Circular Dichroism for the Assignment of Absolute Configuration of Natural Products in Brazil

Valverde

2021

Rev. Bras. Farmacogn.

Phys. Chem. Chem. Phys.

“…While this sensitivity can be exploited to characterize interactions in asymmetric catalysis [8][9][10][11][12][13] and biomolecules, 14,15 solute-solvent hydrogen bonding may cause unforeseen effects on the VCD spectra. 16,17 During an AC assignment, such solvent-influences are often discovered by accident; that means when the spectra calculations on the isolated target molecule do not match with the experimental signatures. In the computations, the solutesolvent hydrogen bond is then considered a posteriori by systematically placing solvent molecules near hydrogen bonding sites of all optimized conformers.…”

Section: Introductionmentioning

confidence: 99%

Solvation of the Boc–Val–Phe–nPr peptide characterized by VCD spectroscopy and DFT calculations

Scholten

Merten

2022

Self Cite

“…This is a crucial step in reliably extracting structural information including absolute configuration and conformation of chiral molecules, such as chiral drugs. [7] antibiotic, [8] cyclic peptides, [9] and amino acids and their derivatives [10,11] from chiral vibrational data.…”

Section: Introductionmentioning

confidence: 99%

“…In general, protic solvents, such as water and methanol, may interact significantly with chiral soluble molecules through medium to strong hydrogen bonding interactions which may lead to noticeable structural changes of the solute molecules [8] and even chirality transfer to surrounding water molecules. [12,13] To extract structural properties from chiral vibrational measurements, the accuracy of spectral simulations is, not surprisingly, a limiting factor.…”

Section: Introductionmentioning

confidence: 99%

Raman Optical Activity of N‐Acetyl‐L‐Cysteine in Water and in Methanol: The “Clusters‐in‐a‐Liquid” Model and ab Initio Molecular Dynamics Simulations

et al. 2022

Raman and Raman Optical Activity (ROA) spectra of N-acetyl-Lcysteine (NALC), a flexible chiral molecule, were measured in water and in methanol to evaluate the solvent effects. Two different solvation approaches, that is, the DFT based "clustersin-a-liquid" solvent model and the ab initio molecular dynamics (AIMD) simulations, were applied to simulate the Raman and ROA spectra. Systematic conformational searches were carried out using a recently developed conformational searching tool, CREST, with the inclusion of polarizable continuum model of water and of methanol. The CREST candidates of NALC and the NALC-solvent complexes were re-optimized and their Raman and ROA simulations were done at the B3LYPÀ D3BJ/def2-TZVP and the B3LYP-aug-cc-pVDZ//cc-pVTZ levels. Also, AIMD simulations, which includes some anharmonic effects and all intermolecular interactions in solution, were performed. By empirically weighting the computed Raman and ROA spectra of each conformer, good agreements with the experimental data were achieved with both approaches, while AIMD offered some improvements in the carbonyl and in the low wavenumber regions over the static DFT approach. The pros and cons of these two different approaches for accounting the solvent effects on Raman and ROA of this flexible chiral system will also be discussed.