Determination of the Absolute Configurations of Chiral Drugs Using Chiroptical Spectroscopy

Polavarapu, Prasad L.

doi:10.3390/molecules21081056

Cited by 37 publications

(30 citation statements)

References 82 publications

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“…Nowadays, the use of chromatography separation of enantiomers on chiral stationary phases is still the approach most often applied in modern chemical research [ 7 , 8 ]. However, the search for new chiral discriminating procedures that allow for quick analysis, high resolution, and utility for many non-volatile or thermally unstable compounds is increasing [ 9 , 10 , 11 , 12 ]. Among the several stereodiscrimination methods, including X-ray, circular dichroism, fluorescence spectroscopy, and electrophoresis, nuclear magnetic resonance (NMR) spectroscopy continues to be a useful tool for determining the enantiomeric purity and assigning the absolute configuration of chiral molecules [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in Multinuclear NMR Spectroscopy for Chiral Recognition of Organic Compounds

Silva

2017

Molecules

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Nuclear magnetic resonance (NMR) is a powerful tool for the elucidation of chemical structure and chiral recognition. In the last decade, the number of probes, media, and experiments to analyze chiral environments has rapidly increased. The evaluation of chiral molecules and systems has become a routine task in almost all NMR laboratories, allowing for the determination of molecular connectivities and the construction of spatial relationships. Among the features that improve the chiral recognition abilities by NMR is the application of different nuclei. The simplicity of the multinuclear NMR spectra relative to 1H, the minimal influence of the experimental conditions, and the larger shift dispersion make these nuclei especially suitable for NMR analysis. Herein, the recent advances in multinuclear (19F, 31P, 13C, and 77Se) NMR spectroscopy for chiral recognition of organic compounds are presented. The review describes new chiral derivatizing agents and chiral solvating agents used for stereodiscrimination and the assignment of the absolute configuration of small organic compounds.

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Section: Introductionmentioning

confidence: 99%

Recent Advances in Multinuclear NMR Spectroscopy for Chiral Recognition of Organic Compounds

Silva

2017

Molecules

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“…These papers, with software available from Gaussian 95, established a baseline for the accurate calculation of VCD spectra in which MFP theory is used for the atomic axial tensors together with direct derivatives and gauge‐invariant atomic orbitals (GIAOs) at the 6‐31G(d) level and the hybrid functionals B3LYP or B3PW91. Since this landmark advance, a number of reviews have been written that featured the use of VCD for the determination of AC in molecules of sufficient size as to be appropriate for chiral organic drug molecules under development . Today, virtually all major pharmaceutical companies and many smaller ones are using VCD as a preferred method for the determination of AC …”

Section: Voa Applications and Enhanced Voamentioning

confidence: 99%

“…In general, solving the complete stereochemistry problem involves determining the correct diastereomer if more than one unknown chiral center is present and determining an accurate Boltzmann distribution of conformers present. In recent years, significant progress has been achieved in the calculating, for example ROA, ECD, and/or ORD, spectra which can independently report on the AC and conformational distribution of a unknown sample …”

Section: Future Development and Challenges For Voamentioning

confidence: 99%

Vibrational optical activity: From discovery and development to future challenges

Nafie

2020

Chirality

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Vibrational optical activity (VOA) consisting of infrared vibrational circular dichroism (VCD) and vibrational Raman optical activity (ROA) was predicted, discovered, and confirmed between 1971 and 1975. My path to VOA was mentored by three pioneers of chirality and vibrational spectroscopy: Professors Albert Moscowitz, Warner L. Peticolas, and Philip J. Stephens, and while they are no longer alive today, the Chirality Medal, my award address, and this paper are dedicated to each of them. Since the discovery of VOA, a number of key advances have made possible the current era of widespread applications. The principal instrumental advances were Fourier-transform VCD (FT-VCD) and multichannel charge coupled detector (CCD) ROA. Computational advances include the first complete quantum chemistry formulation of VCD leading to the magnetic field perturbation (MFP) and the nuclear velocity perturbation (NVP) theories. The strength of VOA is the comparison between measured and calculated spectra that enables the determination of absolute configuration and solution-state conformations. More recently, VCD has uncovered supramolecular chirality in amyloid fibrils and ROA to high-order protein structure. Future challenges for VOA include describing the effects of weak intermolecular interactions, transfer of chirality, solvent effects, supramolecular chirality, and the generation of nuclear velocity electron current density. K E Y W O R D S vibrational circular dichroism (VCD), Raman optical activity (ROA)

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“…Nelson H. Morgon * ,a of the absolute configuration assignments and to help in the discrimination among multiple diastereomers, how described by Polavarapu and co-workers. 13,14 (…”

Section: Iran Da L Sousa a Gabriel Heerdt B Valdecir F Ximenes Cmentioning

confidence: 99%

TD-DFT Analysis of the Dissymmetry Factor in Camphor

Sousa¹,

Heerdt²,

Ximenes³

et al. 2020

J. Braz. Chem. Soc.

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The fact that the dissymmetry factor (g-factor) of camphor is large has been known for decades, and the interpretation of the observed data has also been known for a long time. However, due to the ability of quantum chemical methods to describe chiroptical phenomena more appropriately, additional approaches based on these methods have been successful employed. The g-factor present in S-camphor and L-tryptophan have been investigated by UV-Vis and electronic circular dichroism (ECD) spectroscopies of the n → π* electronic transition. Time-dependent density functional theory (TD-DFT) calculations at CAM-B3LYP/6-311++G(3df,2p)//B3LYP/6-311++G(2d,p) level of theory including Grimme's dispersion effects have been performed. The solvent effect was added using solvation model based on density (SMD) approach in solvation environment. The results permit insights into the ground and excited states electronic properties associated with the g-factor. The theoretical spectra showed good similarity with the experimental ones. The theoretical ECD of camphor was found at 282 nm, whereas the experimental shows its maximum at 290 nm. Regarding the maximum value of the molar absorptivity coefficient, the theoretical and experimental values were 16.2 and 30.2 M-1 cm-1 , respectively. The same concordance was obtained for g-factor, as follows: −0.0445 and −0.0886, for experimental and theoretical results, respectively.

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Determination of the Absolute Configurations of Chiral Drugs Using Chiroptical Spectroscopy

Cited by 37 publications

References 82 publications

Recent Advances in Multinuclear NMR Spectroscopy for Chiral Recognition of Organic Compounds

Recent Advances in Multinuclear NMR Spectroscopy for Chiral Recognition of Organic Compounds

Vibrational optical activity: From discovery and development to future challenges

TD-DFT Analysis of the Dissymmetry Factor in Camphor

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