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In this work, the known and unknown structural as well as biological properties of 3-(2-aminoethyl) indole (tryptamine) were interpreted using molecular spectroscopy (FT-IR, FT-Raman, NMR and UV–Visible) and cheminformatic tools. The supportive drug-related information was gained by analysing the obtained data which will be useful for the drug chemist for the pharmaceutical research. The important biological properties of the present chemical species satisfied the Lipinski five rules and it was opt to fabricate complex antibiotic compounds. The acquired charge potential load for creating antibiotic strain on compositional parts was keenly observed from the obtained data and it was evaluated by the vibrational analysis and Mulliken charge profile. From the NMR data, the chemical nodal points were noted and their movement around the molecule was carefully monitored. The degenerate and non-degenerate energy profile of orbital interaction system was studied and the link of chemical reactivity path was identified. The significance of excited electronic transitions among non-bonding molecular orbital system was justified and their transitional energy coefficient was determined. The toxicity level was checked from the chirality characteristics and enantiomer structure obtained from vibrational circular dichroism profile.

We report the first fully ab initio calculation of dynamical vibrational circular dichroism spectra in the liquid phase using nuclear velocity perturbation theory (NVPT) derived electronic currents. Our approach is rigorous and general and thus capable of treating weak interactions of chiral molecules as, e.g., chirality transfer from a chiral molecule to an achiral solvent. We use an implementation of the NVPT that is projected along the dynamics to obtain the current and magnetic dipole moments required for accurate intensities. The gauge problem in the liquid phase is resolved in a twofold approach. The electronic expectation values are evaluated in a distributed origin gauge, employing maximally localized Wannier orbitals. In a second step, the gauge invariant spectrum is obtained in terms of a scaled molecular moments, which allows to systematically include solvent effects while keeping a significant signal-to-noise ratio. We give a thorough analysis and discussion of this choice of gauge for the liquid phase. At low temperatures, we recover the established double harmonic approximation. The methodology is applied to chiral molecules ((S)-d2-oxirane and (R)-propyleneoxide) in the gas phase and in solution. We find an excellent agreement with the theoretical and experimental references, including the emergence of signals due to chirality transfer from the solute to the (achiral) solvent. [ABSTRACT FROM AUTHOR]

Four types of tris-chelate ruthenium complexes bearing acetylacetonato (acac) and tropolonato (trop) ligands were synthesized and optically resolved into Δ and Λ isomers: [Ru(acac)3] (Ru-0), [Ru(acac)2(trop)] (Ru-1), [Ru(acac)(trop)2] (Ru-2), and [Ru(trop)3] (Ru-3). Chiral HPLC chromatograms, electronic circular dichroism (ECD), and vibrational circular dichroism (VCD) of the four ruthenium complexes were systematically investigated. As a result, the absolute configurations of the newly prepared enantiomeric complexes Ru-2 and Ru-3 were determined. For the case of Ru-2, its absolute configuration was also confirmed by single crystal X-ray diffraction analysis. The ECD changes upon chemical oxidation were further investigated for the four complexes. An ECD change in enantiomeric Ru-1 was observed upon oxidation, but the oxidized species soon returned to the neutral state within a few minutes. Enantiomers of Ru-3 also showed explicit ECD changes upon oxidation. Further, the lifetime of the oxidized state was the longest among the four investigated complexes, whereas they racemized in solution at room temperature. In contrast, the enantiomers of heteroleptic complexes (Ru-1 and Ru-2) concurrently exhibited ECD changes, relatively long lifetime of the oxidized state, and nil or quite slow racemization behavior. The coexistence of acac and trop ligands was key to making the competing factors compatible in the resultant ruthenium complexes. [ABSTRACT FROM AUTHOR]

The experimental vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) spectra were measured for the enantiomers of [1]rotaxane 1. These experimental spectra have been analyzed using predicted VCD and ECD spectra for (S, Rmp) or (S, Smp) diastereomers using density functional theory. This comparison allowed for a definitive assignment of the absolute configuration of 1. [ABSTRACT FROM AUTHOR]

The coordinatively unsaturated bis-chelated iridium(III) complex, [Ir(2-Bubzq)2Cl] (2-BubzqH = 2-butyl-benzo[h]quinoline), denoted as complex 1, was obtained by reacting iridium(III) trichloride with 2-BubzqH in a 1 : 2 molar ratio. The results were in contrast to the common view that a chlorine-bridged dimer, [Ir(L)2Cl]2 (L = bis-chelate ligand), is formed under the corresponding conditions. A single-crystal X-ray diffraction structural analysis revealed that complex 1 has a five-coordinate geometry with a distorted square pyramidal configuration. The optical resolution of complex 1 was measured chromatographically on a chiral column, yielding Δ and Λ as enantiomers. The resolved enantiomers were stable enough against racemization in CDCl3 as confirmed by the vibrational circular dichroism measurements. Complex 1 reacted with carbon monoxide (CO) to give [Ir(2-Bubzq)2(CO)Cl] and with 1,10-phenanthroline (phen) to give [Ir(2-Bubzq)2(phen)]Cl within a minute with its absolute configuration (ΔΛ chirality) maintained. [ABSTRACT FROM AUTHOR]

Mechanically Interlocked Molecules (MIMs), such as catenanes, knots, and rotaxanes, are a class of molecules that possess mechanical bonds. These bonds constitute an entanglement in space between components of the MIMs that cannot be separated without breaking a participating covalent bond. Although it is possible to synthesize chiral MIMs with covalent stereogenic centers, this new bond opens up the possibilities of axial, planar and helical chirality, as well as topologically chiral compounds. A growing number of chiral MIMs have been investigated and employed in numerous applications, ranging from sensing to catalysis. While the investigation of the properties of MIMs is highly developed, it is also essential to study their chiroptical properties. In this review, we focus on the chiroptical properties of chiral MIMs. We discuss their electronic circular dichroism (ECD) since these properties have been analyzed in some detail in relation to their structures and stereochemistry. Although only a few examples have been described to date, we discuss the encouraging circularly polarized luminescence (CPL) properties of MIMs. The review also includes a recent study of vibrational circular dichroism (VCD) in mechanically planar chiral rotaxanes suggesting that this technique is a promising tool for analyzing the structures of MIMs. The study of the chiroptical properties of MIMs can have a large impact on their use in materials science or as catalysts. One of the key advantage of chiral MIMs is that they provide a means of generating efficient chiroptical switches that have a bright future in the context of multiple applications. [ABSTRACT FROM AUTHOR]

This review addresses the synthesis of enantiopure cryptophane and the study of their chiroptical properties. Cryptophane derivatives represent an important class of macrocyclic compounds that can bind a large range of species in solution under different conditions. The overwhelming majority of these host molecules is chiral, and their chiroptical properties have been thoroughly investigated. The first part of this review is dedicated to the optical resolution and the synthesis of enantiopure cryptophane derivatives. In a second part, the study of the chiroptical properties of these molecular hosts by different techniques such as electronic and vibrational circular dichroism and Raman optical activity is detailed. These techniques allow the determination of the absolute configuration of cryptophane derivatives and provide useful information about their conformation in different conditions. [ABSTRACT FROM AUTHOR]

Microcrystals of l‐Asn‐d‐Trp‐l‐Phe‐NH2 (NdWFamide), a tripeptide derived from Aplysia kurodai that exhibits invertebrate cardiac activity, were evaluated by vibrational circular dichroism (VCD). The chirality of the tryptophan residue at the second position in NdWFamide was associated with the conformation and biological characteristics. The VCD spectrum of NdWFamide was a mirror image of its enantiomer; however, it was significantly different from that of its diastereomer, NWFamide, which is its precursor. The obtained VCD signals of NdWFamide were in good agreement with the VCD signals that were calculated based on the optimized aggregates of NdWFamide, which formed a helical‐like backbone conformation. The evaluation of the VCD results revealed the conformation of NdWFamide in the crystalline state and succeeded in distinguishing its stereoisomers. Therefore, this study demonstrates VCD as a useful method for the structural analysis of naturally occurring d‐amino acid‐containing peptides. [ABSTRACT FROM AUTHOR]

Hybrid silica‐organic nanohelices are used to organize a large variety of nonchiral small organic molecules or inorganic anions to nanometer‐sized assemblies. Such chiral organization of achiral molecules induces chiroptical properties as detected by vibrational or electronic circular dichroism (CD), as well as from circularly polarized luminescence (CPL). [ABSTRACT FROM AUTHOR]

The nuclear velocity perturbation theory (NVPT) for vibrational circular dichroism (VCD) is derived from the exact factorization of the electron-nuclear wave function. This new formalism offers an exact starting point to include correction terms to the Born-Oppenheimer (BO) form of the molecular wave function, similar to the complete-adiabatic approximation. The corrections depend on a small parameter that, in a classical treatment of the nuclei, is identified as the nuclear velocity. Apart from proposing a rigorous basis for the NVPT, we show that the rotational strengths, related to the intensity of the VCD signal, contain a new contribution beyond-BO that can be evaluated with the NVPT and that only arises when the exact factorization approach is employed. Numerical results are presented for chiral and non-chiral systems to test the validity of the approach. [ABSTRACT FROM AUTHOR]

[Display omitted] • Full DFT optimization and IR-VCD spectral of α-helical 25-mer peptides. • Effects of geometry, solvation and functional tested on computed spectra. • Improved isotopic substitution spectral patterns require longer length models. • Length limits suggested for transfer of parameters with different interpretive goals. Vibrational circular dichroism (VCD) spectra have been computed with qualitatively correct sign patterns for α-helical peptides using various methods, ranging from empirical models to ab initio quantum mechanical computations. However, some details, such as deuteration effects and isotope substitution shifts and sign patterns for the resultant amide I' band shape, have remained a predictive challenge. Fully optimized computations for a 25-residue Ala-rich peptide, including implicit solvent corrections and explicit side chains that experimentally stabilize these model helical peptides in water, have been carried out using density functional theory (DFT). These fully minimized structures show minor changes in the (ϕ,ψ) torsions at the termini and yield an extra negative band to the low energy side of the characteristic amide I' couplet VCD, in agreement with experiments. Additionally, these calculations give the right sign and relative intensity patterns, as compared to experimental results, for several 13C=O substituted variants. The differences from previously reported computations that used ideal helical structures and vacuum conditions imply that inclusion of distorted termini and solvent effects can have an impact on the final detailed spectral patterns. Inclusion of side chains in these calculations had very little effect on the computed amide I' IR and VCD. Tests of constrained geometries, varying dielectric, and different functionals indicate that each can affect the band shapes, particularly for the 12C=O components, but these aspects do not fully explain the difference from previous spectral simulations. Inclusion of long-range amide coupling, as obtained from DFT computation of the full structure, or transfer of parameters from a somewhat longer peptide model, rather than shorter model, seems to be more important for the final detailed band shape under isotopic substitution. However, these corrections can also induce other changes, suggesting that previously reported, limited calculations may have been qualitatively useful due to a balance of errors. This may also explain the success of simple empirical IR models. [ABSTRACT FROM AUTHOR]

Vibrational analysis plays a crucial role in the investigation of molecular systems. Though methodologies like second-order vibrational perturbation theory (VPT2) have paved the way to more accurate simulations, the computational cost remains a difficult barrier to overcome when the molecular size increases. Building upon recent advances in the identification of resonances, we propose an approach making anharmonic simulations possible for large-size systems, typically unreachable by standard means. This relies on the fact that, often, only portions of the whole spectra are of actual interest. Therefore, the anharmonic corrections can be included selectively on subsets of normal modes directly related to the regions of interest. Starting from the VPT2 equations, we evaluate rigorously and systematically the impact of the truncated anharmonic treatment onto simulations. The limit and feasibility of the reduced-dimensionality approach are detailed, starting on a smaller model system. The methodology is then challenged on the IR absorption and vibrational circular dichroism spectra of an organometallic complex in three different spectral ranges. [Display omitted] • Anharmonic VPT2 simulations of large systems. • Reduced-dimensionality scheme for anharmonic spectra of large systems with VTP2. • Simple indicators to evaluate a priori the impact of truncated anharmonicity terms. • New strategies to obtain converged spectra within selected spectral ranges. • First anharmonic IR and VCD spectra of large ruthenium carbonyl complexes. [ABSTRACT FROM AUTHOR]

[Display omitted] • Coordination and structures of Mo/V/Fe homocitrates and their homologs are reviewed. • The absolute configurations of Mo/V-homocitrates are assigned including those of FeMo/V-cos. • The bond distances of Mo/V-homocitrates are compared with those in FeMo/V-cos. Homocitrate is an organic component in the active site of nitrogenases (N 2 ase), where their cofactors are in the forms of [Δ-MoFe 7 S 9 C(R -Hhomocit)(N-his)(S-cys)], [Δ-VFe 7 S 8 C(CO 3)(R -Hhomocit/homocit)(N-his)(S-cys)], and [Δ-FeFe 7 S 9 C(R -Hhomocit/homocit)(N-his)(S-cys)] (FeMo/V/Fe-cos) respectively, which are based on high-resolution crystallography, XES (XES = X-ray Emission Spectroscopy), ESEEM (ESEEM = Electron Spin Echo Envelope Modulation), and cryogenic electron microscopy. The protonated form of FeMo-co is set up on IR (Infra-red), VCD (Vibrational Circular Dichroism) spectroscopies and the comparisons of model complexes with protein structures in different oxidation states. Homocitrate ligand coordinates with molybdenum through its α-alcoholic and vicinal carboxyl groups, which is served as a possible proton source during the N 2 reduction. Here a brief review has been given on the isolations, spectroscopies and structural characterizations of molybdenum and vanadium homocitrates and their homologs, including citrates, malates, tartrates, lactates and glycolates. The structures and configurations of Mo/V-homocitrato complexes are compared with the coordination environments of molybdenum, vanadium and iron atoms in FeMo/V/Fe-cos. Theoretical calculations for the protonation of α-alkoxido group in homocitrate of FeMo-co were also reviewed. A delivery pathway of hydrogen is suggested for the protonation and deprotonation of homocitrate in FeMo/V-cos. [ABSTRACT FROM AUTHOR]

[Display omitted] • Dutasteride as a model for demonstrating the utility of solid-state VCD for solvatomorphs study. • VCD is a complementary technique for identifying and differentiating several forms of API. • Solid-state VCD is a powerful tool to distinguish solvatomorphs. • Computational study of clusters of solvatomorphs can replicate features of the VCD spectrum. Here, we present the new application of solid-state Vibrational Circular Dichroism (VCD) spectroscopy to differentiate several dutasteride (DS) solvatomorphs – the model active pharmaceutical ingredient (API). Several crystalline DS hydrochloride hydrates solvated with methanol, ethanol, acetonitrile, acetone, and acetic acid were prepared. In contrast to almost identical IR spectra, the VCD ones were very sensitive to changes in the sample composition. We marked significant differences in the shape of VCD spectra of studied DS solvatomorphs, DS hydrates, and DS polymorphic forms. Our findings, supported by DFT calculations, show that VCD spectroscopy has the pronounced ability to distinguish their crystal arrangements. We believe that this contribution will extend the use of VCD in the pharmaceutical industry for developing and designing new chiral drug products for the identification, description, and in-depth probing of several pharmaceutical solvatomorphs in the future. [ABSTRACT FROM AUTHOR]

A novel α-tetrazole-substituted 1,1′-binaphthylazepine chiral catalyst has been synthesized and its absolute configuration has been determined by DFT computational analysis of the vibrational circular dichroism (VCD) spectrum of its precursor. The VCD analysis, carried out through the model averaging method, allowed to assign the absolute configuration of a benzylic stereocenter in the presence of a chiral binaphthyl moiety. The 1,1′-binaphthylazepine tetrazole and the nitrile its immediate synthetic precursor, have been preliminarily tested as chiral organocatalysts in the asymmetric intramolecular oxa-Michael cyclization of 2-hydroxy chalcones for the synthesis of chiral flavanones obtaining low enantioselectivity.

The straightforward, multigram‐scale synthesis of the partially saturated H6‐fluoreno[n]helicenes (n=5 or 7) featuring a central, overcrowded alkene is described. The key cyclization step was based on an intramolecular McMurry reaction from the corresponding 1,5‐diketones. Chiral stationary phase HPLC analysis and isomer separation indicate that each helicenic compound is constituted of three diastereoisomers at room temperature, i. e. the configurationally stable (R,R,P)/(S,S,M) pair of enantiomers and an apparently achiral compound resulting from the rapid interconversion between the (R,S,P) and (S,R,M) enantiomers. The partially saturated H6‐fluoreno[n]helicenes are oxidatively aromatized to give an efficient access to the corresponding fluoreno[n]helicenes. The chiroptical properties (vibrational and electronic circular dichroism) of the chiral, enantiopure compounds have been measured and analyzed by quantum‐chemical calculations, confirming their helicoidal nature. [ABSTRACT FROM AUTHOR]

Chiral perovskites have emerged as a significant class of materials showing promising optoelectronic and spintronic applications. Reports of chiral perovskite ferroelectrics, however, have been scarce. In this work, we have successfully synthesized homochiral lead–iodide perovskite ferroelectrics [(R)‐N‐(1‐phenylethyl)ethane‐1,2‐diaminium]PbI4 and [(S)‐N‐(1‐phenylethyl)ethane‐1,2‐diaminium]PbI4 by introducing a methyl group into the organic cation of the parent (N‐benzylethane‐1,2‐diaminium)PbI4. Vibrational circular dichroism spectra identify the chiral mirroring relationship. They both undergo 222F2‐type paraelectric–ferroelectric behavior at around 378 K coupled with clear ferroelastic domain "ON/OFF" switching. Besides, they exhibit an evident thermochromism with color change from orange–yellow to orange–red. To our knowledge, the discovery of integrated ferroelectricity, ferroelasticity, and reversible thermochromism in chiral perovskites is unprecedented. [ABSTRACT FROM AUTHOR]

Sesquitepenoids inuloxins A–D, belonging to different subgroups, were isolated from Dittrichia viscosa and showed potential biocontrol of some parasitic plants as Pelipanche, Orobanche, and Cuscuta species. The absolute configurations of the first three inuloxins A–C were previously determined by using experimental and computational chiroptical spectroscopic methods. The absolute configuration of inuloxin D remains to be established. The bioactive inuloxin E, closely related to inuloxin D, was recently isolated from the same plant organic extract. The same relative configuration of inuloxin D was assigned to inuloxin E by comparison of their NMR spectroscopic data. The absolute configurations of inuloxin D and inuloxin E are suggested in this work by analysis of the experimental and predicted chiroptical properties of the 4‐O‐acetyl derivative of inuloxin D. [ABSTRACT FROM AUTHOR]

Oxidative stress can lead to various derivatives of the tyrosine residue in peptides and proteins. A typical product is 3-nitro-L-tyrosine residue (Nit), which can affect protein behavior during neurodegenerative processes, such as those associated with Alzheimer's and Parkinson's diseases. Surface enhanced Raman spectroscopy (SERS) is a technique with potential for detecting peptides and their metabolic products at very low concentrations. To explore the applicability to Nit, we use SERS to monitor tyrosine nitration in Met-Enkephalin, rev-Prion protein, and α-synuclein models. Useful nitration indicators were the intensity ratio of two tyrosine marker bands at 825 and 870 cm−1 and a bending vibration of the nitro group. During the SERS measurement, a conversion of nitrotyrosine to azobenzene containing peptides was observed. The interpretation of the spectra has been based on density functional theory (DFT) simulations. The CAM-B3LYP and ωB97XD functionals were found to be most suitable for modeling the measured data. The secondary structure of the α-synuclein models was monitored by electronic and vibrational circular dichroism (ECD and VCD) spectroscopies and modeled by molecular dynamics (MD) simulations. The results suggest that the nitration in these peptides has a limited effect on the secondary structure, but may trigger their aggregation. [ABSTRACT FROM AUTHOR]

Flexible molecules and non‐idle environments can present severe problems in the prediction of vibrational spectra. This work focuses on infrared and vibrational circular dichroism for which the latter is extremely sensitive to such complicated situations. Here two possible ways to perform spectroscopy calculations for such situations are investigated. The first approach is based on static quantum chemical calculations employing cluster‐weighting. The second approach is rooted in ab initio molecular dynamics simulations using the time correlations approach. For the present example ((R)‐butan‐2‐ol), excellent spectra from simulations are obtained for gas and bulk, when the former is averaged over trajectories with all possible starting conformers and these are scaled to match the experimental spectrum. The cluster‐weighted approach is inferior to the simulations but still reaches very good results at much less computational cost. A simplified, but computationally less expensive simulation approach is considered by approximating the electric and magnetic moments, which are input quantities in the correlation function, by classical equations and different populations analysis for the required partial charges. The results are inferior to the full simulations but still give satisfying results at the advantage of being much faster to calculate. [ABSTRACT FROM AUTHOR]

A series of functionalized quinoline‐based aromatic oligoamide foldamers were prepared in their two enantiomeric forms, comprising an enantiopure terminal camphanyl chiral inducer, which governed the adjacent (P‐/M‐) helical‐handedness. Hierarchical chirality transfer was further investigated in chromophore‐appended variants via a range of electronic and vibrational spectroscopic techniques, including circularly polarized luminescence, vibrational circular dichroism and fluorescence. Intense total and polarized photoluminescence (up to Φlum=0.39, glum=1.5×10−3) was observed in the visible region from these modular multicomponent architectures and a significant influence of positional isomerism was evidenced. The optimal position of a fluorophore substituent on the quinoline hexamers was determined as being position 2 over position 6, as stronger chiroptical features were systematically observed with the 2‐positioned derivatives. [ABSTRACT FROM AUTHOR]

Although demonstrated in 1975, vibrational circular dichroism (VCD) finally started to popularize during this century as a reliable tool to determine the absolute configuration (AC) of organic molecules. This research field continues to be a very dynamic one, in particular for the study of natural products which are a unlimited source of chiral molecules. It therefore turns of interest to summarize the accomplishments published in recent years and to comment on some eventual difficulties that emerged in rare cases to complete the AC determination task. Therefore the aim of this review is to update VCD results for the AC assignment of natural products published from 2015 to 2019, a period in which VCD was reported in some 126 publications involving almost 300 molecules. They are organized according the type of studied metabolite allowing an easily search. The molecules correspond to 28 monoterpenes concerning 17 papers, to 42 sesquiterpenes in 14 papers, to 51 diterpenes in 19 publications, to 5 other terpenoids in three papers, to 48 aromatic molecules in 15 reports, to 20 polyketides in 10 publications, to 27 miscellaneous formulas also in 10 papers, and to 76 nitrogen containing compounds, which include alkaloids and their synthetic analogs, in 38 articles. The landscape of reviewed molecules is quite wide as it goes from simple monoterpenes, like borneol or camphor, to very relevant biological molecules like the alkaloid cocaine or tadalafil samples to distinguish genuine and counterfeit Cialis®. In addition, 5 natural products and a simple derivative published outside the reviewed period, were used to illustrate some aspects of density functional theory calculations. [ABSTRACT FROM AUTHOR]

In the corrected theoretical spectrum, the experimental finding is reproduced in the sense that the G-mode band has a slightly higher intensity than the D-mode band. In the original theoretical spectrum (incident laser wavelength I i = 540 nm), the G-mode band was predicted to be of weaker intensity than the D-mode band, in contradiction to the experimental finding. We previously reported calculations of the Raman optical activity (ROA) spectrum of an iron-alkynyl-helicene complex (labeled B 2a b in the original article). [Extracted from the article]

These days, single-crystal X-ray analysis is a routine method that not only allows the elucidation of the stereostructures of individual molecules but also gives insights regarding the crystal structures hiding symmetry/asymmetry-related issues. One of the most relevant fields includes optical activity that is the consequence of a kind of chirality center, such as an asymmetric C atom, while a heteroatom, like P. Atrop isomerism, may also be a reason. All kinds of symmetry-related problems in organic and inorganic chemistry may be the subject of papers submitted to I Symmetry i . [Extracted from the article]

The optical purity of a chiral sample is of particular importance to the analytical chemistry and pharmaceutical industries. In recent years, the vibrational optical activity (VOA) has become established as a sensitive and nondestructive technique for the analysis of chiral molecules in solution. However, the relatively limited accuracy in the range of about 1–2% reported in published papers and the relatively small spread of experimental facilities to date have meant that vibrational spectroscopy has not been considered a common method for determining enantiomeric excess. In this paper, we attempt to describe, in detail, a methodology for the determination of enantiomeric excess using Raman optical activity (ROA). This method achieved an accuracy of 0.05% for neat α-pinene and 0.22% for alanine aqueous solution, after less than 6 h of signal accumulation for each enantiomeric mixture, which we believe is the best result achieved to date using vibrational optical activity techniques. An algorithm for the elimination of systematic errors (polarization artifacts) is proposed, and the importance of normalizing ROA spectra to correct for fluctuations in excitation power is established. Results comparable to those obtained with routinely used chemometric analysis by the partial least squares (PLS) method were obtained. These findings show the great potential of ROA spectroscopy for the quantitative analysis of enantiomeric mixtures.

The minimum chemical modification that can be incorporated into an organic molecule is the replacement of a hydrogen atom for a deuterium atom. This change is not altering the pharmacological properties of a molecule, although it provides the possibility of making specific spectroscopic evaluations. Thus, in the present study, we explore how a stereogenic center is influenced by such an isotopic labeling. The studies were conducted on both enantiomers of flavanone (1 and 2) which is the parent molecule of a large group of pharmacologically active natural occurring secondary metabolites. Flavanone comprised 12 carbon atoms forming two benzene rings, a carbonyl group, an ethereal oxygen atom, a methylene group, and only one C–H stereogenic center, so it seems to be an ideal candidate for such studies. Density functional theory (DFT) calculations were used for the accurate prediction of vibrational circular dichroism (VCD) spectra of (R)‐(3) and (S)‐flavanone‐2‐d (4), of (R)‐(5) and (S)‐flavanone‐3,3‐d2 (6), and of (R)‐(7) and (S)‐flavanone‐2′,3′,4′,5′,6′‐d5 (8). To gain compounds that provide experimental VCD spectra for comparative purposes, the calculated spectra of both enantiomers of the corresponding flavanones, obtained after HPLC separation of the racemates by means of a chiral column, were contrasted, thereby revealing excellent agreements when using the CompareVOA software. In addition, the VCD spectra of both unlabeled enantiomeric flavanones (1 and 2) were also compared to the labeled molecules, revealing that the VCD spectra show significant variations induced by the deuterium incorporation. [ABSTRACT FROM AUTHOR]

Chiral zirconium(IV) double cage sandwich complex Zr(1)2 has been synthesized in one step from porphyrin cage H21. Zr(1)2 was obtained as a racemate, which was resolved by HPLC and the enantiomers were isolated in >99.5% ee. Their absolute configurations were assigned on the basis of X-ray crystallography and circular dichroism spectroscopy. Vibrational circular dichroism (VCD) experiments on the enantiomers of Zr(1)2 revealed that the chirality around the zirconium center is propagated throughout the whole cage structure. The axial conformational chirality of the double cage complex displayed a VCD fingerprint similar to the one observed previously for a related chiral cage compound with planar and point chirality. Zr(1)2 shows fluorescence, which is quenched when viologen guests bind in its cavities. The binding of viologen and dihydroxybenzene derivatives in the two cavities of Zr(1)2 occurs with negative allostery, the cooperativity factors α (= 4 K2/K') being as low as 0.0076 for the binding of N,N'-dimethylviologen. These allosteric effects are attributed to a pinching of the second cavity as a result of guest binding in the first cavity. [ABSTRACT FROM AUTHOR]

New psychoactive substances (NPSs) have become a popular alternative to illicit drugs of abuse. However, to determine their metabolic pathways in the human organism, a detailed knowledge of their structure is crucial. Here, we present a comprehensive spectroscopic structural study of synthetic cathinones (clephedrone, flephedrone, and brephedrone) and their major human metabolites, desmethyl derivatives. Chiral high-performance liquid chromatography was utilized to obtain the individual enantiomers of the parent synthetic cathinones and their assumed major metabolites synthesized de novo. The developed chromatographic method made it possible to obtain the target optically pure substances on a multimilligram scale. Electronic and vibrational circular dichroism, combined with infrared and ultraviolet spectroscopy and supported by DFT calculations, were used to determine their absolute configuration and the chiroptical methods to elucidate their molecular structure in detail. Two stable conformers of each substance were found in aqueous solution. Their relative abundances were estimated based on the Boltzmann distribution and the population weighted spectra were obtained. Very good agreement was achieved between the experimental and simulated spectra, enabling the 3D structures of the studied substances to be determined in aqueous solution. [ABSTRACT FROM AUTHOR]

The four new briarane diterpenoids 2-butyryloxybriarane B-3 (2), 9-acetylbriarenolide S (3), briarenolide W (4), and 12-isobriarenolide P (5), along with briarane B-3 (1) and the five known diterpenes 6–10 were isolated from the gorgonian coral Briareum asbestinum collected from the Mexican Caribbean Sea. The structures were elucidated by 1D and 2D NMR and MS measurements. Since the structure of briarane B-3 (1) was only suggested and published without any spectroscopic support, it was herein confirmed, and the supporting data are now provided. In addition, 1 provided the opportunity to explore the sensitivity of vibrational circular dichroism (VCD) to determine the configuration of a single stereogenic center in the presence of eight other stereogenic centers in a molecule possessing a highly flexible ten-member ring. A single-crystal X-ray diffraction study, in which the Flack and Hooft parameters of 1 were determined, further confirmed that briarane B-3 is (1S,2S,6S,7R,8R,9S,10S,11R,17R)-1. This paper reports for first time the use of VCD in briarane diterpenes and with the presence of chlorine atoms. Biological evaluation of seven isolated compounds evidenced a moderate anti-inflammatory activity for compounds 6 and 9 but it did not show any cytotoxic, antiviral, antibacterial, and topoisomerase inhibitory activity. [ABSTRACT FROM AUTHOR]

Polarizable force fields are an essential component for the chemically accurate modeling of complex molecular systems with a significant degree of fluxionality, beyond harmonic or perturbative approximations. In this contribution we examine the performance of such an approach for the vibrational spectroscopy of the alanine amino acid, in the gas and condensed phases, from the Fourier transform of appropriate time correlation functions generated along molecular dynamics (MD) trajectories. While the infrared (IR) spectrum only requires the electric dipole moment, the vibrational circular dichroism (VCD) spectrum further requires knowledge of the magnetic dipole moment, for which we provide relevant expressions to be used with polarizable force fields. The AMOEBA force field was employed here to model alanine in the neutral and zwitterionic isolated forms, solvated by water or nitrogen, and as a crystal. Within this framework, comparison of the electric and magnetic dipole moments to those obtained with nuclear velocity perturbation theory based on density-functional theory for the same MD trajectories are found to agree well with one another. The statistical convergence of the IR and VCD spectra is examined and found to be more demanding in the latter case. Comparisons with experimental frequencies are also provided for the condensed phases., (© 2024 The Authors. ChemPhysChem published by Wiley-VCH GmbH.)

This study reports the microscopic measurements of vibrational circular dichroism (VCD) on four different insect wings using a quantum cascade laser VCD system equipped with microscopic scanning capabilities (named multi-dimensional VCD [MultiD-VCD]). Wing samples, including (i) beetle, Anomala albopilosa (female), (ii) European hornet, Verspa crabro flavofasciata Cameron, 1903 (female), (iii) tiny dragonfly, Nannophya pygmae Rambur, 1842 (male), and (iv) dragonfly, Symetrum gracile Oguma, 1915 (male), were used in this study. Two-dimensional patterns of VCD signals (~10 mm × 10 mm) were obtained at a spatial resolution of 100 μm. Measurements covered the absorption peaks assigned to amides I and II in the range of 1500-1740 cm -1 . The measurements were based on the enhancement of VCD signals for the stereoregular linkage of peptide groups. The patterns were remarkably dependent on the species. In samples (i) and (ii), the wings comprised segregated domains of protein aggregates of different secondary structures. The size of each microdomain was approximately 100 μm. In contrast, no clear VCD spectra were detected in samples (iii) and (iv). One possible reason was that the chain of stereoregular polypeptides was too short to achieve VCD enhancement in samples (iii) and (iv). Notably, the unique features were only observed in the VCD spectra because the IR spectra were nearly the same among the species. The VCD results hinted at the connection of protein microscopic structures with the wing flapping mechanisms of each species., (© 2024 Wiley Periodicals LLC.)

The differential response of chiral molecules to incident left- and right-handed circularly polarized light is used for sensing the handedness of molecules. Currently, significant effort is directed toward enhancing weak differential signals from the molecules, with the goal of extending the capabilities of chiral spectrometers to lower molecular concentrations or small analyte volumes. Previously, optical cavities for enhancing vibrational circular dichroism have been introduced. Their enhancements are mediated by helicity-preserving cavity modes which maintain the handedness of light due to their degenerate TE and TM components. In this article, we simplify the design of the cavity and numerically compare it with the previous one using an improved model for the response of chiral molecules. We use parameters of molecular resonances to show that the cavities are capable of bringing the vibrational circular dichroism signal over the detection threshold of typical spectrometers for concentrations that are one to three orders of magnitude smaller than those needed without the cavities, for a fixed analyte volume. Frequency resolutions of current spectrometers result in enhancements of more than one order (two orders) of magnitude for the new (previous) design. With improved frequency resolution, the new design achieves enhancements of three orders of magnitude. We show that the TE/TM degeneracy in perfectly helicity-preserving modes is lifted by factors that are inherent to the cavities. More surprisingly, this degeneracy is also lifted by the molecules themselves due to their lack of electromagnetic duality symmetry, that is, due to the partial change of helicity during the light-molecule interactions. [ABSTRACT FROM AUTHOR]

Covering: 2015 to up to 2019 This review presents the recent progress towards elucidating the structures of chiral natural products and applications using vibrational optical activity (VOA) spectroscopy. Vibrational circular dichroism (VCD) and vibrational Raman optical activity (VROA) are two separate branches of VOA spectroscopy, providing independent and complementary structural information. While determining the absolute configuration (AC) of a given natural product is the primary goal, the determination or assessment of major conformations associated with each diastereomer is also a significant part of this enquiry. The latest developments in experimental and computational aspects of VOA spectroscopies and their applications for inferring the AC and predominant conformations of natural products are summarized. The prospects and limitations in the application of VOA spectroscopy to new natural products are summarized. [ABSTRACT FROM AUTHOR]

Bromuconazole is a potent triazole fungicide and consists of two pairs of enantiomers [trans(2R, 4R)-, trans(2S, 4S)-configurations and cis(2R, 4S), cis(2S, 4R)-configurations]. The degradation of the enantiomers of (2RS, 4RS)- and (2RS, 4SR)-bromuconazole by phase I metabolism was investigated using rat, mouse, rabbit, dog and human liver microsomes. Bromuconazole isomers were quantified using HPLC-MS/MS (ESI+) after the separation on a combination of a reversed phase and a chiral analytical column. Moreover, the absolute configuration of four enantiomers had been determined based on the comparisons of the vibrational circular dichroism experimental spectra with the theoretical curve obtained by density functional theory calculations. The degradation of all four isomers followed first-order kinetics and the (2R, 4S)-bromuconazole displayed a significantly longer half-life during microsomal incubation than that of other antipodes. Moreover the metabolic rates of four isomers in human and mouse were much slower than those in rat, rabbit and dog, indicating species-specific differences in the metabolism of bromuconazole. The Vmax values for (2S, 4R)-bromuconazole were obviously higher than those of its antipode in all liver microsomes studied. The Vmax values for (2R, 4R)-bromuconazole were significantly higher than those for (2S, 4S)-bromuconazole in all liver microsomes studied except human. [ABSTRACT FROM AUTHOR]

The structural characterization of non-covalent complexes between nucleic acids and small molecules (ligands) is of a paramount significance to bioorganic research. Highly informative methods about nucleic acid/ligand complexes such as single crystal X-ray diffraction or NMR spectroscopy cannot be performed under biologically compatible conditions and are extensively time consuming. Therefore, in search for faster methods which can be applied to conditions that are at least similar to the naturally occurring ones, a set of polarization spectroscopy methods has shown highly promising results. Electronic circular dichroism (ECD) is the most commonly used method for the characterization of the helical structure of DNA and RNA and their complexes with ligands. Less common but complementary to ECD, is flow-oriented linear dichroism (LD). Other methods such as vibrational CD (VCD) and emission-based methods (FDCD, CPL), can also be used for suitable samples. Despite the popularity of polarization spectroscopy in biophysics, aside several highly focused reviews on the application of these methods to DNA/RNA research, there is no systematic tutorial covering all mentioned methods as a tool for the characterization of adducts between nucleic acids and small ligands. This tutorial aims to help researchers entering the research field to organize experiments accurately and to interpret the obtained data reliably.

The synthesis of chiral metal–organic frameworks (MOFs) is highly relevant for asymmetric heterogenous catalysis, yet very challenging. Chiral MOFs with MOF‐74 topology were synthesised by using post‐synthetic modification with proline. Vibrational circular dichroism studies demonstrate that proline is the source of chirality. The solvents used in the synthesis play a key role in tuning the loading of proline and its interaction with the MOF‐74 framework. In N,N′‐dimethylformamide, proline coordinates monodentate to the Zn2+ ions within the MOF‐74 framework, whereas it is only weakly bound to the framework when using methanol as solvent. Introducing chirality within the MOF‐74 framework also leads to the formation of defects, with both the organic linker and metal ions missing from the framework. The formation of defects combined with the coordination of DMF and proline within the framework leads to a pore blocking effect. This is confirmed by adsorption studies and testing of the chiral MOFs in the asymmetric aldol reaction between acetone and para‐nitrobenzaldehyde. [ABSTRACT FROM AUTHOR]

In this Minireview, we summarize our recent efforts to use vibrational circular dichroism (VCD) spectroscopy, the chiroptical version of IR spectroscopy, for the characterization of conformational preferences of asymmetric catalysts and complexes, formed upon the respective interactions or reactions of catalysts with substrates. After giving a brief overview of the general aspects of the technique, we showcase how VCD spectra of a chiral ion‐pairing catalyst could be used to confirm a conformational shifting mechanism that determines the enantioselectivity of the catalyst. Chiral thioureas serve as examples for hydrogen bonding organocatalysts for which we demonstrate that both conformational preferences of the catalysts as well as of the hydrogen‐bonded complexes with substrates can be obtained from a detailed computational spectra analysis. Jørgensen–Hayashi‐type prolinol ether catalysts serve as examples to introduce experimental challenges associated with catalysts that operate by covalent activation of reactants. [ABSTRACT FROM AUTHOR]

Recently, we reported a three-dimensional phase diagram for the gelation of cationic tripeptide glycylalanylglycine (GAG) in water–ethanol mixtures. We showed that the gel strength reaches an optimum for a peptide concentration of 200 mM and ethanol/water mixtures with ca. 55–60 mol% ethanol. An increase of the ethanol fraction causes a substantial upshift of the gel's softening temperature which is indicative of a reduced peptide solubility. We expect the formation of long crystalline fibrils which form the sample spanning network of the gel phase to precede the gelation process and that the fibril microstructure depends on the rate and concentration of peptide. We used UV circular dichroism (UVCD) spectroscopy to probe the kinetics of GAG fibril formation as a function of peptide concentration and ethanol fraction. We provide experimental evidence for the notion that the utilized CD signal reflects the three-dimensional assembly of peptides rather than a two-dimensional sheet structure. UVCD was also used to probe the melting of GAG fibrils with increasing temperature. FTIR and vibrational circular dichroism (VCD) spectroscopy were employed to characterize the structure of sheets with which the observed fibrils were formed. Fibrilization and gelation kinetics occur on a very similar time scale for very short gelation times (<7 min) observed at high peptide concentrations and/or ethanol fractions. Otherwise, gelation proceeds significantly slower than fibrilization. The trends in the UVCD spectral response parallel the trends in the storage modulus as a function of peptide concentration and ethanol fraction. IR and VCD profiles of amide I′ reveal that fibril structure and the respective chirality are both affected by peptide concentration and solvent composition. At high ethanol fractions, the VCD changes its sign suggesting a conversion from phase II to phase I. Generally, the latter is obtained only at temperatures below 15 °C. Altogether, our results reveal how GAG fibrilization and gelation are interrelated and how the gel properties can be tuned by changing the composition of the ternary GAG/water/ethanol mixture. [ABSTRACT FROM AUTHOR]