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This paper is dedicated to the quantum chemical package Jaguar, which is commercial software developed and distributed by Schrödinger, Inc. We discuss Jaguar's scientific features that are relevant to chemical research as well as describe those aspects of the program that are pertinent to the user interface, the organization of the computer code, and its maintenance and testing. Among the scientific topics that feature prominently in this paper are the quantum chemical methods grounded in the pseudospectral approach. A number of multistep workflows dependent on Jaguar are covered: prediction of protonation equilibria in aqueous solutions (particularly calculations of tautomeric stability and pKa), reactivity predictions based on automated transition state search, assembly of Boltzmann-averaged spectra such as vibrational and electronic circular dichroism, as well as nuclear magnetic resonance. Discussed also are quantum chemical calculations that are oriented toward materials science applications, in particular, prediction of properties of optoelectronic materials and organic semiconductors, and molecular catalyst design. The topic of treatment of conformations inevitably comes up in real world research projects and is considered as part of all the workflows mentioned above. In addition, we examine the role of machine learning methods in quantum chemical calculations performed by Jaguar, from auxiliary functions that return the approximate calculation runtime in a user interface, to prediction of actual molecular properties. The current work is second in a series of reviews of Jaguar, the first having been published more than ten years ago. Thus, this paper serves as a rare milestone on the path that is being traversed by Jaguar's development in more than thirty years of its existence. [ABSTRACT FROM AUTHOR]

Chiral hybrid perovskites (CHPs) with inherent chirality, dimensional tunability, and excellent semiconducting features are proved to be an ideal platform to study spin and helicity‐related physical phenomenon. However, due to their intrinsic thermodynamic unfavorability, there are many CHPs with exotic structures, such as superlattice‐type 2D heterostructures, which are covered by their transient lifespan caused by phase instability during the crystallization process. This limitation hinders the attempt to further explore and understand the chiral structure‐function relationship. Here, CHPs (R/SCPEA)2PbI4·(R/SCPEA)2FAPb2I7 (R/S1‐2, R/S‐CPEA = (R/S)‐1‐(4‐chlorophenyl)ethylammonium FA = formidinum) is obtained with asymmetric multiple‐quantum‐well architectures through kinetically‐controlled self‐assembly. Structural analysis identified the unique natural monolayer‐bilayer recurring heterostructures of 1–2 with sub‐nanometer accuracy and potentially non‐degenerate chiral environment. Such novel structures in 1–2 provide them fascinating multiple absorption‐emission features. Meanwhile, the chirality of 1–2 is confirmed by vibrational circular dichroism and angle‐dependent photocurrent measurement, provoking its potential in chiral optoelectronic devices. The work extends the understanding of CHP growth and will stimulate further exploration and synthesis of extraordinary chiral heterostructures, which may pave the way for the development of chiral optoelectronics and spintronics. [ABSTRACT FROM AUTHOR]

Hydantoins, a class of five-membered heterocyclic compounds, exhibit diverse biological activities. The aim of this study was to synthesize and characterize a series of novel 3,5-disubstituted hydantoins and to investigate their antiproliferative activity against human cancer cell lines. The new hydantoin derivatives 5a–i were prepared as racemic mixtures of syn- and anti-isomers via a base-assisted intramolecular amidolysis of C-3 functionalized β-lactams. The enantiomers of syn-5a and anti-hydantoins 5b were separated by preparative high-performance liquid chromatography (HPLC) using n-hexane/2-propanol (90/10, v/v) as the mobile phase. The absolute configuration of the four allyl hydantoin enantiomers 5a was assigned based on a comparison of the experimental electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) spectra with those calculated using density functional theory (DFT). The antiproliferative activity evaluated in vitro against three different human cancer cell lines: HepG2 (liver hepatocellular carcinoma), A2780 (ovarian carcinoma), and MCF7 (breast adenocarcinoma), and on the non-tumor cell line HFF1 (normal human foreskin fibroblasts) using the MTT cell proliferation assay. In silico drug-like properties and ADMET profiles were estimated using the ADMET Predictor ver. 9.5 and the online server admetSAR. Eighteen new 3,5-disubstituted hydantoins were synthesized and characterized. The compound anti-5c showed potent cytotoxic activity against the human tumor cell line MCF7 (IC50 = 4.5 µmol/L) and the non-tumor cell line HFF1 (IC50 = 12.0 µmol/L). In silico analyzes revealed that the compounds exhibited moderate water solubility and membrane permeability and are likely substrates for CYP3A4 and P-glycoprotein and have a high probability of antiarthritic activity. [ABSTRACT FROM AUTHOR]

The document is the contents list for an issue of the journal Chemical Communications. It includes various articles and communications on topics such as biocatalysis, stereochemistry of natural products, enzyme design, coordination-cage based catalysis, and more. The journal is published by The Royal Society of Chemistry, a leading chemistry community. The document provides a glimpse into the research and advancements in the field of chemistry. [Extracted from the article]

Secondary metabolites from land and marine (micro)organisms have been at the focus of the drug discovery process for many years. One of the reasons for this success is nature's incredible ability to create intricate molecular scaffolds. Such structural richness, however, makes the structural elucidation, and the absolute configuration assignment in particular, a challenging process. Vibrational circular dichroism (VCD) has emerged as one of the most reliable and versatile methods to unambiguously assign both the absolute configuration and conformations of chiral molecules in solution. Although VCD is no longer a curiosity in the field of molecular spectroscopy after 50 years since its first report, it is still underutilized by natural product chemists worldwide for varying reasons. Herein, we highlight the evolution of the application of VCD to natural product chemistry, focusing on its strengths as well as points that still need improvement. General guidelines for the correct application of VCD to stereochemical studies are also provided. [ABSTRACT FROM AUTHOR]

We recently reported on 8 different pentameric oligothiophenes, denoted proteophenes, with different amino acid substitution patterns along the conjugated thiophene backbone. The proteophenes were forming chiral both molecular (solvent dissolved) and self‐assembled nano‐architectonic structures, the latter having approximately 5–6 times greater ICD responses. Herein, two proteophenes, HS‐84‐E−E and HS‐84‐K−K, were further investigated in terms of binding to two chiral variants of insulin amyloid fibrils. Binding curves based on fluorescence revealed strong primary binding sites for both proteophenes and more unspecific secondary binding for especially the latter. Interestingly, their induced circular dichroism (ICD) responses were similar to or stronger than for their solvent form and showed a complicated alteration upon binding suggesting that the microstructure at the binding site governs the helical structure of the ligand. Hyperspectral fluorescence microscopy and FLIM revealed more details on the molecular binding in terms of proteophene emission decay‐times. Vibrational circular dichroism (VCD) analysis showed that VCD signal of amyloid fibrils was enhanced upon binding of proteophenes, suggesting changes in the amyloid microstructures. [ABSTRACT FROM AUTHOR]

Recently, the control of dynamic chirality has emerged as a powerful strategy to design chiral functional materials. In this context, we describe herein a molecular design in which a tethered configurationally stable binaphthyl chiral unit efficiently controls the dynamic chirality of donor‐acceptor fluorophores, involving diverse indolocarbazoles as electron donors and terephthalonitrile as an electron acceptor. The high conformational discrimination in such a molecular system suggested by density functional theory calculations is experimentally probed using electronic and vibrational circular dichroism and confirmed by the crystallization of these chiral molecules in gel and their single crystal X‐ray diffraction analysis. This work also highlights the positive effect of the configurationally stable chiral unit on the magnitude of the dissymmetry factors of the active dynamically chiral fluorophores, both in ground and excited states, through chiral perturbation. [ABSTRACT FROM AUTHOR]

Rotational circular dichroism (RCD) has not been observed yet, but it is expected to deliver information about chiral molecules useful in many branches of chemistry. In the past, rather weak RCD intensities were predicted for model diamagnetic molecules and a limited number of rotational transitions. Here, we review quantum-mechanical foundations and simulate entire spectral profiles, including larger molecules, open-shell molecular radicals, and high-momentum rotational bands. Contribution of the electric quadrupolar moment was considered, but it turned out that it does not contribute to field-free RCD. Two conformers of a model dipeptide provided clearly distinct spectra. The dissymmetry Kuhn parameter gK predicted for the diamagnetic molecules even for high-J transitions rarely exceeded 10−5, and the simulated RCD spectra were often biased to one sign. In the radicals, the coupling of the rotational angular momentum with the spin for some transitions raised gK to about 10−2, and the RCD pattern was more conservative. In the resultant spectra, many transitions had negligible intensities due to small populations of the involved states, and a convolution with a spectral function made the typical RCD/absorption ratios about 100-times smaller (gK ∼ 10−4). This is still comparable with values typical for electronic or vibrational circular dichroism, and paramagnetic RCD is thus likely to be measurable relatively easily. [ABSTRACT FROM AUTHOR]

Proline is a unique amino acid in that its side-chain is cyclised to the backbone, thus giving proline an exceptional rigidity and a considerably restricted conformational space. Polyproline forms two well-characterized helical structures: a left-handed polyproline helix (PPII) and a right-handed polyproline helix (PPI). Usually, sequences made only of prolyl residues are in PPII conformation, but even sequences not rich in proline but which are rich in glycine, lysine, glutamate, or aspartate have also a tendency to form PPII helices. Currently, the only way to study unambiguously PPII structure in solution is to use spectroscopies based on optical activity such as circular dichroism, vibrational circular dichroism and Raman optical activity. The importance of the PPII structure is emphasized by its ubiquitous presence in different organisms from yeast to human beings where proline-rich motifs and their binding domains are believed to be involved in vital biological processes. Some of the domains that are bound by proline-rich motifs include SH3 domains, WW domains, GYF domains and UEV domains, etc. The PPII structure has been demonstrated to be essential to biological activities such as signal transduction, transcription, cell motility, and immune response. [ABSTRACT FROM AUTHOR]

With the rapid development of high performance computers and computational methods, including software, an increasing number of experimental chemists have tried to use computational methods such as optical rotation (OR, including the matrix model), optical rotatory dispersion (ORD), electronic circular dichroism (ECD or CD), vibrational circular dichroism (VCD), and magnetic shielding constants--nuclear magnetic resonance (NMR)--to explain and/or assign absolute configuration (AC) for various compounds. Such reports in the field of natural products have increased dramatically. However, every method has its range of application. This leads, in some cases, to incorrect conclusions by researchers who are not familiar with these methods. In this review, we provide experimental chemists and researchers with more computational details and suitable suggestions, and especially hope that this experience may help readers avoid computational pitfalls. Finally, we discuss the use of simplified models to replace original complex structures with a long side chain. The fundamental basis for using models to represent complex chiral compounds, such as in OR calculations, is the existence of conformation pairs with near canceling conformer contributions that justify the use of models rather than the original compounds. Using examples, we here introduce the transition state (TS) calculation, which may benefit readers in this area for use and mastery for their AC study. This review will summarize the general concepts involved in the study of AC determinations. [ABSTRACT FROM AUTHOR]

Amyloid fibrils are supramolecular systems showing distinct chirality at different levels of their complex multilayered architectures. Due to the regular long‐range chiral organization, amyloid fibrils exhibit the most intense Vibrational Optical Activity (VOA) signal observed up to now, making VOA techniques: Vibrational Circular Dichroism (VCD) and Raman Optical Activity (ROA) very promising tools to explore their structures, handedness and intricate polymorphism. This concept article reviews up‐to‐date experimental studies on VOA applications to investigate amyloid fibrils highlighting its future potential in analyzing of these unique supramolecular systems, in particular in the context of biomedicine and nanotechnology. [ABSTRACT FROM AUTHOR]

Vibrational circular dichroism (VCD) spectra of chiral high‐spin organic radicals are expected to show a strong intensity enhancement and are thought to be difficult to predict using state‐of‐the‐art theoretical methods. Herein we show that the chiral triplet nitrene obtained from photochemical cleavage of N2 from enantiopure 2‐azido‐9H‐fluorenol does not feature extraordinarily strong intensities and that the experimental spectra match nicely with calculated ones. Thereby, this study demonstrates the general feasibility of studies on chiral high‐spin organics by matrix‐isolation VCD. [ABSTRACT FROM AUTHOR]

This article reports the synthesis of the two enantiomers of a water‐soluble cryptophane 3 enabling cesium and thallium complexation at neutral or basic pH. The two enantiomers of 3 were obtained in a two steps synthesis from cryptophane 4, a molecule decorated with three phenol groups and three other phenol groups protected by benzyl units. The two enantiomers of 4 were isolated from liquid chromatography using chiral stationary phase. The absolute configuration of the two enantiomers of 3 was determined by vibrational circular dichroism combined with theoretical calculations. Contrary to cryptophane 1 that present large spectroscopic changes upon cesium and thallium complexation, the electronic circular dichroism spectra of compound 3 exhibit moderate spectral changes suggesting that this compound cannot change the conformation of its linkers as easily as cryptophane 1. [ABSTRACT FROM AUTHOR]

Objective: Determine the structure, absolute configuration, and antiproliferative activity of a new furan diterpenoid isolated from the leaves of Coulteria velutina (Britton & Rose) Sotuyo & G.P.Lewis (Fabaceae). Methods: The structures of the natural product and those of 2 derivatives were established mainly by nuclear magnetic resonance spectroscopy, while their absolute configurations were established using vibrational circular dichroism involving comparison of the experimental and calculated spectra of a rigid derivative. Results: Isolation of (−)-(4 R,5 R,6 R,8 S,9 S,10 R,14 R)-6-[(E)- p -coumaroyloxy]vouacapan-18-oic acid (1), an undescribed secondary metabolite from the leaves of C velutina, is reported hereafter. Hydrolysis of 1 provided (+)-(4 R,5 R,6 R,8 S,9 S,10 R,14 R)-6-hydroxyvouacapan-18-oic acid (2), identical to a diterpenoid isolated from Caesalpinia echinata, but whose absolute configuration remained undetermined. Subsequent lactonization of 2 yielded (+)-(4 R,5 R,6 R,8 S,9 S,10 R,14 R)-vouacapan-6,18-olide (3). The absolute configurations of compounds 1 – 3 were established by vibrational circular dichroism studies of 3. In addition, the antiproliferative activity of the natural product 1 against HeLa, MDA-MB-231, Caco-2, and NIH/3T3 cell lines is reported. Conclusions: The leaves of C velutina yielded the new vouacapane 1. It showed weak antiproliferative activity against HeLa and MDA-MB-231 cancer cell lines (IC50 = 92.2 and 106.2 μg/mL, respectively), but was also weakly active against the NIH/3T3 healthy cell line (IC50 value of 127.6 µg/mL). Its absolute configuration was determined by vibrational circular dichroism analysis of the conformationally rigid compound 3. This derivative can be used as a reference for the absolute configuration of related vouacapanes. In addition, this is the first phytochemical investigation of C velutina. [ABSTRACT FROM AUTHOR]

Optically active left (M)‐ and right (P)‐handed helical syndiotactic poly(methyl methacrylate)s (M‐ and P‐st‐PMMAs) with a helicity memory enantioselectively encapsulated the racemic C60 derivatives, such as 3,4‐fulleroproline tert‐butyl ester (rac‐1) and tetraallylated C60 (rac‐2), as well as the C60‐bound racemic 310‐helical peptides (rac‐3) within their helical cavities to form peapod‐like inclusion complexes and a unique "helix‐in‐helix" superstructure, respectively. The enantiomeric excess (ee) and separation factor (enantioselectivity) (α) of the analyte 1 (ee = 23%–25% and α = 2.35–2.50) encapsulated within the helical cavities of the M‐ and P‐st‐PMMAs were higher than those of the analytes 2 and 3 (ee = 4.3%–6.0% and α = 1.28–1.50). The optically pure (S)‐ and (R)‐1 were found to more efficiently induce an excess one‐handed helical conformation in the st‐PMMA backbone than the optically pure (S)‐ and (R)‐1‐phenylethylamine, resulting in intense mirror‐image vibrational circular dichroism (VCD) spectra in the PMMA IR regions. The excess one‐handed helices induced in the st‐PMMAs complexed with (S)‐ and (R)‐1 were memorized after replacement with the achiral C60, and the complexes exhibited induced electric CDs in the achiral C60 chromophore regions. [ABSTRACT FROM AUTHOR]

We computed vibrational circular dichroism (VCD) and Raman optical activity (ROA) spectra for a test set of six chiral compounds using two standard density-functionals and an array of basis sets. We analysed the performance of property-oriented basis sets using a quadruple-zeta basis as a reference against four key metrics. We find little qualitative difference between the spectra produced by the larger basis sets (ORP, LPolX, aug-cc-pVTZ, and aug-cc-pVQZ), though their quantitative metrics exhibit wide variations. The smaller basis sets (rDPS, augD-3-21G, augT3-3-21G, Sadlej-pVTZ, and aug-cc-pVDZ) performed better for VCD rotatory strengths than for the corresponding ROA circular intensity differences (CIDs). However, this trend diminishes as the basis-set size is increased, lending validity to the conclusion that more robust property-oriented basis sets are required for ROA spectral generation than that of VCD. We observed improved performance in the mid-infrared region compared to the high-frequency regime, as well as overestimation of VCD rotatory strengths in the latter region as compared to the reference. We conclude that the ORP and LPol-ds basis sets are the most efficient and effective choices of basis set for the prediction of VCD and ROA spectra, as they provide both highly accurate results at reduced computational expense. [ABSTRACT FROM AUTHOR]

Chiral metamaterials play vital roles in manipulating the circular polarization of electromagnetic waves. Although planar chiral metamaterials are believed to have no true/intrinsic chirality, the design of structural anisotropy can still create enormous circular dichroism, while the mechanism is fully explored. Here, for the first time, it is observed that strong near‐field coupling induces less chiral response in chiral metamaterials. Selective exposure methods to manipulate the near‐field coupling strength, and experimentally validate the circular dichroism difference from tailored near‐field coupling effect are leveraged, which provides strong evidence for the assumption and can be utilized for the structural design framework. Besides, using the enhanced near‐field (over 750‐fold), surface‐enhanced vibrational circular dichroism (SEVCD) for glucose enantiomers, which shows a larger‐than‐one normalized sensitivity compared with metamaterials with chiral response is demonstrated. Furthermore, The potential of SEVCD by detecting a broadband signal using arrayed metamaterials is explored. These findings pave the way toward chiroptical nanophotonic designs for potential biomedical and healthcare applications. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Five diastereomers of ruthenium(II) complexes based on quinolinophaneoxazoline ligands were investigated by vibrational circular dichroism (VCD) in the mid‐IR and CH stretching regions. Diastereomers differ in three sources of chirality: the planar chirality of the quinolinophane moiety, the central chirality of an asymmetric carbon atom of the oxazoline ring, and the chirality of the ruthenium atom. VCD, allied to DFT calculations, has been found to be effective in disentangling the various forms of chirality. In particular, a VCD band is identified in the CH stretching region directly connected to the chirality of the metal. The analysis of the calculated VCD spectra is carried out by partitioning the complexes into fragments. The anharmonic analysis is also performed with a recently proposed reduced‐dimensionality approach: such treatment is particularly important when examining spectroscopic regions highly perturbed by resonances, like the CH stretching region. [ABSTRACT FROM AUTHOR]

The influence of phosphorus substitution of nitrogen in heterocyclic compounds on the vibrational spectroscopy as well as frontier molecular orbitals are analyzed. Nicotine with two nitrogen atoms in its structure is taken as the sample system to be studied computationally. By replacing the nitrogen atom in one or both rings of this molecule with phosphorus, three nicotine derivatives are created. The vibrational circular dichroism and infrared spectra of these four molecules in their monomer state, as well as the assemblies up to trimers are determined. The aforementioned spectra are calculated using static quantum chemical calculations employing a cluster‐weighted approach. The calculated gas phase spectra of nicotine are compared to their respective experimental spectra. It is observed that the nicotine derivatives with phosphorus in the methylpyrrolidine ring have considerably different gas phase and bulk phase vibrational circular dichroism spectra when compared to nicotine. The phosphorus substitution reduces the energy gap between the highest occupied molecular orbital and the lowest unoccupied molecular orbital as well as altering the polarizability and reactivity of the investigated molecules. [ABSTRACT FROM AUTHOR]

Peyssonnoside A is an unusual natural product consisting of a diterpene unit and a sulfonated monosaccharide. The experimental and theoretical comparison of Optical Rotatory Dispersion (ORD) and quantitative Nuclear Magnetic Resonance (NMR) data provided strong evidence for the stereochemistry of the diterpene unit. However, predicted Vibrational Circular Dichroism (VCD) spectra of Peyssonnoside A at the B3LYP/6-311++G(2d,2p) level showed poor correlation to the corresponding experimental spectra, preventing independent absolute configuration (AC) determination from VCD analysis. New calculations using the B3PW91 functional and the 6-311G(3df,2pd) basis set suggest that we can now independently and confidently assign the AC of Peyssonnoside A through VCD analyses. The use of f-polarization functions is responsible for the current successful assignment, compared to previously failed VCD analysis. This study highlights two important points: (a) the importance of using multiple levels of theories for satisfactorily reproducing the experimental spectra and (b) for quantitative comparisons using similarity indices, it is important to consider not only the VCD spectra but also the corresponding absorption spectra. [ABSTRACT FROM AUTHOR]

Chiral imidazole-based oxidovanadium tartrates (H2im)2[Δ,Λ-VIV2O2(R,R-H2tart)(R,R-tart)(Him)2]·Him (1, H4tart = tartaric acid, Him = imidazole) and [Λ,Λ-VIV2O2(R,R-tart)(Him)6]·4H2O (2) and their corresponding enantiomers (H2im)2[Λ,Δ-VIV2O2(S,S-H2tart)(S,S-tart)(Him)2]·Him (3) and [Δ,Δ-VIV2O2(S,S-tart)(Him)6]·4H2O (4) were obtained in alkaline solutions. Interestingly, the tartrates chelate with vanadium bidentately through α-alkoxy/α-hydroxy and α-carboxy groups and imidazole coordinates monodentately through nitrogen atom. It is worth noting that complexes 1 and 3 contain both protonated α-hydroxy and deprotonated α-alkoxy groups simultaneously, which have short V–Oα-alkoxy distances [1.976(4)av Å in 1–4] and long V–Oα-hydroxy distances [2.237(3)av Å in 1 and 2.230(2)av Å in 3]. There is an interesting strong intramolecular hydrogen bond [O(11)⋯O(1) 2.731(5) Å] between the two parts in 1 and 3. The protonated V–O distances are closer to the average bond distance in reported FeV-cofactors (FeV-cos, V–Oα-alkoxy 2.156av Å) in VFe proteins, which corresponds to the feasible protonation of coordinated α-hydroxy in R-homocitrate in V-nitrogenase, showing the homocitrate in the mechanistic model for nitrogen reduction as a secondary proton donor. Furthermore, vibrational circular dichroism (VCD) and IR spectra of 1–4 pointed out the disparity between the characteristic vibrations of the C–O and C–OH groups clearly. EPR experiment and theoretical calculations support +4 oxidation states for vanadium in 1–4. Solution 13C {¹H} NMR spectra and CV analyses exhibited the solution properties for 1 and 2, respectively, which indicates that there should be a rapid exchange equilibrium between the protonated and deprotonated species in solutions. [ABSTRACT FROM AUTHOR]

Metamaterials with localized surface plasmon resonances have been the subject of intense research for a wealth of applications ranging from active photonic devices to analytical sensing units that utilizes the local field enhancement to improve sensitivity and decrease acquisition time. Herein, we focus on the modelled properties of a series of spiral metastructures that present multiple chiral plasmon modes in the 1–10 μm mid‐IR spectral range and that could be utilized to enhance vibrational circular dichroism measurements to further identify molecular, supramolecular and structural chirality centres. Finite‐difference time‐domain electromagnetic modelling was conducted to calculate the infrared spectra of the metastructures in response to a circularly polarized excitation. Several geometric parameters were altered to further tune the position of the resonances. In addition, the near‐field distribution of the optical resonances was calculated providing a spatial snapshot of the chiral modes. Preliminary spiral structures were fabricated using electron beam lithography and their vibrational circular response was measured. [ABSTRACT FROM AUTHOR]

Recently, high-throughput quantum cascade laser-based vibrational circular dichroism (QCL-VCD) technology has reduced the measurement time for high-quality vibrational circular dichroism spectra from hours to a few minutes. This study evaluates QCL-VCD for chiral monitoring using flow-through measurement of a changing sample in a circulating loop. A balanced detection QCL-VCD system was applied to the enantiomeric pair R/S-1,1′-bi-2-naphthol in solution. Different mixtures of the two components were used to simulate a racemization process, collecting spectral data at a time resolution of 6 min, and over three concentration levels. The goal of this experimental setup was to evaluate QCL-VCD in terms of both molar and enantiomeric excess (EE) sensitivity at a time resolution relevant to chiral monitoring in chemical processes. Subsequent chemometric evaluation by partial least squares regression revealed a cross-validated prediction accuracy of 2.8% EE with a robust prediction also for the test data set (error = 3.5% EE). In addition, the data set was also treated with the least absolute shrinkage and selection operator (LASSO), which also achieved a robust prediction. Due to the operating principle of LASSO, the obtained coefficients constituted a few discrete spectral frequencies, which represent the most variance. This information can be used in the future for dedicated QCL-based instrument design, gaining a higher time resolution without sacrificing predictive capabilities. Graphical abstract This is a visual representation of the abstract. [ABSTRACT FROM AUTHOR]

Utilizing experimental and computational vibrational circular dichroism (VCD) spectroscopy, we explored the conformational preferences of a series of chiral C3‐symmetric octaazacryptands with tris(2‐aminoethyl)‐amine head groups derived from valine. While the spectra of the smallest azacryptand with p‐phenyl linkers and its elongated derivative with p‐biphenyls linker were found to match well with the computed spectra, the computed conformational preferences of the m‐biphenyl‐based azacryptand did not seem to reflect the conformations dominating in chloroform solution. A detailed analysis revealed that structural changes resulting in a collapsed cage structure gave a notably better match with the experiment. It could subsequently be concluded from the VCD analysis, that the octaazacryptands prefer a collapsed structure, which is not predicted by density functional theory (DFT) calculations as the global minimum structures. These findings are expected to have consequences also for future studies on inclusion complexes of such azacryptands. [ABSTRACT FROM AUTHOR]

Instrumental techniques able to identify and structurally characterize the aggregation states in thin films of chiral organic π‐conjugated materials, from the first‐order supramolecular arrangement up to the microscopic and mesoscopic scale, are very helpful for clarifying structure‐property relationships. Chiroptical imaging is currently gaining a central role, for its ability of mapping local supramolecular structures in thin films. The present review gives an overview of electronic circular dichroism imaging (ECDi), circularly polarized luminescence imaging (CPLi), and vibrational circular dichroism imaging (VCDi), with a focus on their applications on thin films of chiral organic dyes as case studies. [ABSTRACT FROM AUTHOR]

Chirality is a curious phenomenon that appears in various forms. While the concept of molecular (RS‐)chirality is ubiquitous in chemistry, there are also more intricate forms of structural chirality. One of them is the enantiomorphism of crystals, especially molecular crystals, that describes the lack of mirror symmetry in the unit cell. Its relation to molecular chirality is not obvious, but still an open question, which can be addressed with chiroptical tools. Vibrational circular dichroism (VCD) denotes chiral infrared (IR) spectroscopy that is susceptible to both, the molecular as well as the intermolecular space by means of vibrational transitions. When carried out in the solid state, VCD delivers a very rich set of non‐local contributions that are determined by crystal packing and collective motion. Since its discovery in the 1970s, VCD has become the method of choice for the determination of absolute configurations, but its applicability reaches beyond towards the study of different crystal forms and polymorphism. This brief review summarises the theoretical concepts of crystal chirality and how computations of solid‐state VCD can shed light into the intimate connection of chiral structure and vibrational optical activity. [ABSTRACT FROM AUTHOR]

An achiral chromophore can acquire a chiral spectroscopic signature when interacting with a chiral environment. This so-called induced chirality is documented in electronic or vibrational circular dichroism, which arises from the coupling between electric and magnetic transition dipoles. Here, we demonstrate that a chiroptical response is also induced within the electric dipole approximation by observing the asymmetric scattering of a photoelectron ejected from an achiral chromophore in interaction with a chiral host. In a phenol–methyloxirane complex, removing an electron from an achiral aromatic π orbital localised on the phenol moiety results in an intense and opposite photoelectron circular dichroism (PECD) for the two enantiomeric complexes with (R) and (S) methyloxirane, evidencing the long-range effect (~5 Å) of the scattering chiral potential. This induced chirality has important structural and analytical implications, discussed here in the context of growing interest in laser-based PECD, for in situ, real time enantiomer determination. An achiral molecule can acquire a chiral spectroscopic signature when interacting with a chiral host. Here, the authors report the asymmetry in the electron distribution following ionisation of phenol complexed by chiral methyloxirane, which reflects an induced chirality onto the achiral phenol. [ABSTRACT FROM AUTHOR]

Although VCD studies on allenes have been reported by other groups, [30] only two reports presented experimental VCD spectra in the C=C=C stretching region. Although a detailed understanding of the VCD properties of allenes requires more studies on other types of allenes (e.g., tri-and tetrasubstituted allenes), our findings should facilitate studies on chiral allenes. Keywords: vibrational circular dichroism; carbodiimides; allenes; axial chirality; structural analysis EN vibrational circular dichroism carbodiimides allenes axial chirality structural analysis 1839 1844 6 09/15/23 20231004 NES 231004 Graph 1 Introduction Vibrational circular dichroism (VCD) spectroscopy has been used to elucidate the stereochemistry and conformation of various natural products and synthetic molecules. [Extracted from the article]

The determination of the absolute configuration (AC) of an organic molecule is still a challenging task for which the combination of spectroscopic with quantum‐mechanical methods has become a promising approach. In this study, we investigated the accuracy of DFT methods (480 overall combinations of 15 functionals, 16 basis sets, and 2 solvation models) to calculate the VCD spectra of six chiral organic molecules in order to benchmark their capability to facilitate the determination of the AC. [ABSTRACT FROM AUTHOR]

The infrared (IR) and vibrational circular dichroism (VCD) spectra of methyl β‐D‐glucopyranose in water were measured. Both implicit and explicit solvation models were utilized to explain the observed spectra. The vast body of existing experimental and theoretical data suggested that about eight explicit water molecules are needed to account for the solvent effects, supported by the current Quantum Cluster Growth (QCG) analysis. Extensive manual and systematic conformational searches of the molecular target and its water clusters were carried out by using a recently developed conformational searching tool, conformer‐rotamer ensemble sampling tool (CREST), and the microsolvation model in the associated QCG code. The Boltzmann averaged IR and VCD spectra of the methyl β‐D‐glucopyranose‐(water)n (n = 8) conformers in the PCM of water provide better agreement with the experimental ones than those with n = 0, 1, and 2. The explicit solvation with eight water molecules was shown to greatly modify the conformational preference of methyl β‐D‐glucopyranose from its monomeric form. Further analyses show that the result is consistent with the existence of long‐lived methyl β‐D‐glucopyranose monohydrates with the additional explicit water effects being accounted for with the quantum mechanical treatment of the other seven close‐by water molecules in the PCM of water. [ABSTRACT FROM AUTHOR]

Amyloid fibrils form remarkable, multi-layered chiral supramolecular architectures. The proximity of interacting oscillators in the chiral fibril supramolecules is responsible for the unusual sensitivity of vibrational circular dichroism (VCD) for fibril formation. Surprisingly, up to now, such characteristics have not been shown for ROA, although it displays the same vibrational markers of fibrils as VCD, including the amide I band. Here, we report an exceptionally large enhancement of the ROA signal detected for mature amyloid fibrils and their prefibrillar states. Remarkably, the same ROA signal has been obtained for fibrils of homologous lysozymes and the dissimilar protein, insulin, indicating a possible common enhanced ROA spectrum, analogous to that for VCD for all amyloid fibrils investigated to date. The ROA signal is observed at earlier stages of fibril formation than VCD and provides access to a considerably broader range of vibrations. Further studies are necessary to verify the applicability of ROA for the analysis of amyloid fibrils. [ABSTRACT FROM AUTHOR]

This work describes an effective method to obtain chiral vinyl cyclopentenols with a high degree of enantioselectivity and diastereoselectivity through Heck desymmetrization of cyclopent‐3‐en‐1‐ylmethanol using vinyl triflates as coupling agents and chiral N,N ligands. This Heck vinylation protocol allowed the synthesis of several structurally complex cyclopentenols in isolated yields of up to 80 % in enantiomeric ratios of up to 97 : 3 and diastereoselectivities higher than 20 : 1 in most cases. Experiments using (E) or (Z) vinyl triflates, and desymmetrization of protected olefin 1‐(cyclopent‐3‐en‐1‐ylmethoxy)‐4‐nitrobenzene (17) were instrumental in rationalizing the observed diastereoselectivities of Heck products involving the interaction of vinyl triflate carbonyl and the hydroxyl group moiety of the substrate with the cationic Pd(II) complex. The absolute configuration of the vinylated Heck products was determined by Vibrational Circular Dichroism (VCD) spectroscopy. [ABSTRACT FROM AUTHOR]

Chirality transfer from the chiral molecule (R)‐1,2‐propylene oxide to the achiral anion of the 1‐ethyl‐3‐methylimidazolium bis(trifluoromethylsulfonyl)imide ionic liquid is observed. The chiral probe selectively affects one part of the binary ionic liquid, i. e., it has previously been shown experimentally and theoretically that this particular imidazolium cation can be affected by chirality transfer, but in the present system chirality is almost exclusively transferred to the anion and not to both parts of the solvent (anion and cation). This observation is of high relevance because of its selectivity and because anion effects are usually much more important in ionic liquid research than cation effects. From ab initio molecular dynamics simulations, a conformational analysis and dissected vibrational circular dichroism spectra are obtained to study the chirality transfer. While in the neat ionic liquid two mirror imaged trans conformers of the anion occur almost equally, we observe an excess of one of these conformers in the presence of the chiral solute, causing optical activity of the anion. Although the cis conformers are not tremendously affected by the chirality transfer, they gain in total population when (R)‐1,2‐propylene oxide is dissolved in the ionic liquid. [ABSTRACT FROM AUTHOR]

The fruitful interplay of high-resolution spectroscopy and quantum chemistry has a long history, especially in the field of small, semi-rigid molecules. However, in recent years, the targets of spectroscopic studies are shifting toward flexible molecules, characterized by a large number of closely spaced energy minima, all contributing to the overall spectrum. Here, artificial intelligence comes into play since it is at the basis of powerful unsupervised techniques for the exploration of soft degrees of freedom. Integration of such algorithms with a two-stage QM/QM′ (Quantum Mechanical) exploration/refinement strategy driven by a user-friendly graphical interface is the topic of the present paper. We will address in particular: (i) the performances of different semi-empirical methods for the exploration step and (ii) the comparison between stochastic and meta-heuristic algorithms in achieving a cheap yet complete exploration of the conformational space for medium sized chromophores. As test cases, we choose three amino acids of increasing complexity, whose full conformer enumeration has been reached only very recently. Next, we show that systems in condensed phases can be treated at the same level and with the same efficiency when employing a polarizable continuum description of the solvent. Finally, the challenging issue represented by the vibrational circular dichroism spectra of some rhodium complexes with flexible ligands has been addressed, showing that our fully unsupervised approach leads to remarkable agreement with the experiment. [ABSTRACT FROM AUTHOR]

TRAVIS ("Trajectory Analyzer and Visualizer") is a program package for post-processing and analyzing trajectories from molecular dynamics and Monte Carlo simulations, mostly focused on molecular condensed phase systems. It is an open source free software licensed under the GNU GPL, is platform independent, and does not require any external libraries. Nine years after the original publication of TRAVIS, we highlight some of the recent new functions and features in this article. At the same time, we shortly present some of the underlying algorithms in TRAVIS, which contribute to make trajectory analysis more efficient. Some modern visualization techniques such as Sankey diagrams are also demonstrated. Many analysis functions are implemented, covering structural analyses, dynamical analyses, and functions for predicting vibrational spectra from molecular dynamics simulations. While some of the analyses are known since several decades, others are very recent. For example, TRAVIS has been used to compute the first ab initio predictions in the literature of bulk phase vibrational circular dichroism spectra, bulk phase Raman optical activity spectra, and bulk phase resonance Raman spectra within the last few years. [ABSTRACT FROM AUTHOR]

Vibrational Circular Dichroism (VCD) spectra often differ strongly from one conformer to another, even within the same absolute configuration of a molecule. Simulated molecular VCD spectra typically require expensive quantum chemical calculations for all conformers to generate a Boltzmann averaged total spectrum. This paper reports whether machine learning (ML) can partly replace these quantum chemical calculations by capturing the intricate connection between a conformer geometry and its VCD spectrum. Three hypotheses concerning the added value of ML are tested. First, it is shown that for a single stereoisomer, ML can predict the VCD spectrum of a conformer from solely the conformer geometry. Second, it is found that the ML approach results in important time savings. Third, the ML model produced is unfortunately hardly transferable from one stereoisomer to another. Vibrational circular dichroism is a spectroscopic technique used to study conformational properties and determine absolute configurations of molecules, but spectra are laborious to interpret. Here, the authors use machine learning to assign absolute configurations and to predict conformer spectra solely from molecular geometries. [ABSTRACT FROM AUTHOR]

The enantioselective synthesis of isoindolones via Heck‐Mizoroki reactions of endocyclic enamides using a palladium‐bis(oxazoline) catalyst system is described. The N,N‐ligands, which are under‐represented in palladium‐catalyzed reactions involving aryl halides, proved to be an effective and low‐cost alternative to their phosphine‐based chiral ligand counterparts. The intramolecular Heck reaction of aryl iodides and endocyclic enamides enabled the construction of tricyclic isoindolones containing tertiary and quaternary chiral centers under mild conditions in yields up to 73 % and enantiomeric ratios up to 97 : 3. Vibrational circular dichroism (VCD) was instrumental in determining the absolute configuration of the enantioenriched isoindolones. [ABSTRACT FROM AUTHOR]

Chirality (C) is a fundamental symmetry property of objects. Detecting and distinguishing molecular chirality in the infrared spectrum is important in life sciences, biology, and chemistry. In this paper, we demonstrate an achiral metasurface based on a gaped dual-germanium-dimer array for enhanced mid-infrared chiral sensing under both circularly polarized light (CPL) and linearly polarized light (LPL) excitations. With the metasurface, strong electric and magnetic dipole resonances with large field enhancement can be generated, resulting in an accessible superchiral hotspot in the dimer gaps under both excitation modes. The maximum electric and magnetic field enhancements exceed 220 and 100 for the bare metasurface, and exceed 70 and 60 for the metasurface coated with a 50 nm chiral biolayer under both excitations, respectively. Importantly, a high volume-averaged C enhancement CE_ave of 241 (444) and CE_ave_bio of 161 (102) under CPL (LPL) excitation can be achieved for the bare metasurface and it coated with the chiral biolayer, respectively. These results may open up new possibilities for ultrasensitive vibrational circular dichroism (VCD) and rotational optical dispersion (ORD) spectroscopy in the mid-infrared range. [ABSTRACT FROM AUTHOR]

Amyloid fibrils are fascinating and complex structures with the multilayered chiral organization. Using the multimodal methodology, including VCD, ECD, cryo‐EM, and TEM, we characterized in detail different levels of organization (secondary structure/protofilament/mesoscopic structure) of amyloid fibrils prepared from proteins highly homologous in the structure (hen egg white and human lysozymes). Our results demonstrate that small changes in the native protein structure or preparation conditions translate into significant differences in the handedness and architecture of the formed fibrils at various levels of their complexity. In particular, fibrils of hen egg white and human lysozymes obtained in vitro at the same preparation conditions, possess different secondary structure, protofilament twist and ultrastructure. Yet, formed fibrils adopted a relatively similar mesoscopic structure, as observed in high‐resolution 3D cryo‐EM, scarcely used up to now for fibrils obtained in vitro in denaturing condition. Our results add to other puzzling experiments implicating the indeterministic nature of fibril formation. [ABSTRACT FROM AUTHOR]

The conformational landscapes of two highly flexible monosaccharide derivatives, namely phenyl β-D-glucopyranoside (ph-β-glu) and 4-(hydroxymethyl)phenyl β-D-glucopyranoside, also commonly known as gastrodin, were explored using a combined experimental and theoretical approach. For the infrared, Raman, and the associated vibrational optical activity (VOA), i.e., vibrational circular dichroism and Raman optical activity, experiments of these two compounds in DMSO and in water were carried out. Extensive and systematic conformational searches were performed using a recently developed conformational searching tool called CREST (conformer-rotamer ensemble sampling tool) in the two solvents. Fourteen and twenty-four low-energy conformers were identified at the DFT level for ph-β-glu and gastrodin, respectively. The spectral simulations of individual conformers were done at the B3LYP-D3BJ/def2-TZVPD level with the polarizable continuum model of the solvents. The VOA spectral features exhibit much higher specificity to conformational differences than their parent infrared and Raman. The excellent agreements achieved between the experimental and simulated VOA spectra allow for the extraction of experimental conformational distributions of these two carbohydrates in solution directly. The experimental percentage abundances based on the hydroxymethyl (at the pyranose ring) conformations G+, G-, and T for ph-β-glu were obtained to be 15%, 75%, and 10% in DMSO and 53%, 40%, and 7% in water, respectively, in comparison to the previously reported gas phase values of 68%, 25%, and 7%, highlighting the important role of solvents in conformational preferences. The corresponding experimental distributions for gastrodin are 56%, 22%, and 22% in DMSO and 70%, 21%, and 9% in water. [ABSTRACT FROM AUTHOR]

Triacetone triperoxide (TATP) and hexamethylene triperoxide diamine (HMTD) are cyclic peroxides that exhibit atropisomerism resulting from restricted rotation around three peroxide bonds. As a result, one pair of enantiomers with D3 symmetry and another pair of enantiomers with C2 symmetry can be identified. Previous studies, based on mass spectrometry data and computational results, have shown that conformations of TATP with D3 and C2 symmetry can be isolated. Assuming that enantiomer samples of TATP and HMTD can be obtained with sufficient enantiopurity, we investigated their chiroptical properties, namely, optical rotatory dispersion (ORD), vibrational circular dichroism (VCD), and Raman optical activity (VROA). ORD curves and VCD spectra are seen to be very similar for D3‐ and C2‐symmetric atropisomers with the same overall helicity. Predicted VROA results, however, show significant differences between D3‐ and C2‐symmetric atropisomers with the same overall helicity. The D3‐symmetric atropisomer is predicted to exhibit considerably larger magnitude vibrational optical activity signals than the C2‐symmetric atropisomer. [ABSTRACT FROM AUTHOR]

After cannabis, the most commonly used illicit substance worldwide is amphetamine and its derivatives, such as methamphetamine, with an ever-increasing number of synthetic modifications. Thus, fast and reliable methods are needed to identify them according to their spectral patterns and structures. Here, we have investigated the use of molecular spectroscopy methods to describe the 3D structures of these substances in a solution that models the physiological environment. The substances were analyzed by Raman and infrared (IR) absorption spectroscopy and by chiroptical methods, vibrational circular dichroism (VCD) and Raman optical activity (ROA). The obtained experimental data were supported by three different computational approaches based on density functional theory (DFT) and molecular dynamics (MD). Successful interpretation relies on good agreement between experimental and predicted spectra. The determination of the conformer populations of the studied molecules was based on maximizing the similarity overlap of weighted conformer spectra by a global minimization algorithm. Very good agreement was obtained between the experimental spectra and optimized-population weighted spectra from MD, providing a detailed insight into the structure of the molecules and their interaction with the solvent. The relative population of three amphetamine and six methamphetamine conformers was determined and is consistent with a previous NMR study. However, this work shows that only a few isolated conformers are not sufficient for the successful interpretation of the spectra, but the entire conformational space needs to be sampled appropriately and explicit interaction with the solvent needs to be included. [ABSTRACT FROM AUTHOR]

Vibrational circular dichroism (VCD) spectroscopy can generate the data required for the assignment of absolute configuration, but the spectra are hard to interpret. We have recorded VCD data for thirty pairs of small organic compounds and we use this database to validate a method for the automated analysis of VCD spectra and the assignment of absolute configuration: the Cai•factor (Configuration: absolute information). The analysis of the data demonstrates that the procedure is a reliable and time-efficient method for determination of absolute configuration, which gives both the assignment and a measure of confidence in the outcome, even when the spectra are imperfect. The majority of molecules tested have a high confidence score and all of these have the correct assignment. [ABSTRACT FROM AUTHOR]

Two transition metal complexes were synthesized with Ni(II) and Cu(II) using a tetradentate Schiff-base ligand, (R,R) and (S,S)-N,N′-Bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamine. The stereochemical properties of the ligand and the metal complexes were investigated using a combined experimental and theoretical approach. Multiple spectroscopic techniques, which include IR, vibrational circular dichroism (VCD), UV-Vis and electronic circular dichroism (ECD), as well as Raman and the newly discovered ECD-circularly polarized Raman (i.e., eCP-Raman) spectroscopies were utilized. The good agreement achieved between the experimental and simulated IR, VCD, UV-Vis and ECD spectra of the ligand allowed one to identify the presence of three main ligand conformers in solution, thanks, especially to the high VCD sensitivity to the conformations associated with the tertbutyl groups. The helicity of the metal complexes was identified to be M and P for those with the (R,R) and (S,S) ligands, respectively. Furthermore, eCP-Raman measurements were carried out for the two metal complexes under (near) resonance. Their induced solvent chiral Raman features were explained, and the potential application of eCP-Raman was discussed. [ABSTRACT FROM AUTHOR]

In this work we review research activities on a few of the most relevant structural aspects of bilirubin (BR) and biliverdin (BV). Special attention is paid to the exocyclic C=C bonds being in mostly Z rather than E configurations, and to the overall conformation being essentially different for BR and BV due to the presence or absence of the double C=C bond at C-10. In both cases, racemic mixtures of each compound of either M or P configuration are present in achiral solutions; however, imbalance between the two configurations may be easily achieved. In particular, results based on chiroptical spectroscopies, both electronic and vibrational circular dichroism (ECD and VCD) methods, are presented for chirally derivatized BR and BV molecules. Finally, we review deracemization experiments monitored with ECD data from our lab for BR in the presence of serum albumin and anesthetic compounds. [ABSTRACT FROM AUTHOR]

The structures and absolute configurations of two organic compounds, excoecoumarin A and excoecoumarin B, were studied by recording their electronic circular dichroism (ECD) spectra and performing quantum‐chemistry computations. The optical rotations and the nuclear magnetic resonance (NMR), ECD, vibrational circular dichroism (VCD), and ultraviolet (UV) spectra of candidate structures were computed using the B3LYP approach of the density functional theory. The structures and absolute configurations of excoecoumarins A and B are inferred from the agreement between the experimental and theoretical NMR, ECD, and UV spectra. Although a specific configuration can be assigned to excoecoumarin A, three structures are possible for excoecoumarin B. The computations indicated that the absolute configuration of excoecoumarin B can be further identified by acquiring the VCD spectra. In any case, the present study indicated that the structures reported previously should be revised. [ABSTRACT FROM AUTHOR]

Peyssonnoside A is an unusual natural product consisting of a diterpene unit and a sulfonated monosaccharide. The experimental and theoretical comparison of Optical Rotatory Dispersion (ORD) and quantitative Nuclear Magnetic Resonance (NMR) data provided strong evidence for the stereochemistry of the diterpene unit. However, predicted Vibrational Circular Dichroism (VCD) spectra of Peyssonnoside A at the B3LYP/6-311++G(2d,2p) level showed poor correlation to the corresponding experimental spectra, preventing independent absolute configuration (AC) determination from VCD analysis. New calculations using the B3PW91 functional and the 6-311G(3df,2pd) basis set suggest that we can now independently and confidently assign the AC of Peyssonnoside A through VCD analyses. The use of f-polarization functions is responsible for the current successful assignment, compared to previously failed VCD analysis. This study highlights two important points: (a) the importance of using multiple levels of theories for satisfactorily reproducing the experimental spectra and (b) for quantitative comparisons using similarity indices, it is important to consider not only the VCD spectra but also the corresponding absorption spectra.

It is very important to assign a stereogenic center in study of the chiral medicines.With the development of calculation methods and software,it is possible to use different theoretical methods to assign the absolute configuration of chiral compounds.Now,the methods are used for different calculation,such as specific optical rotation,optical rotatory dispersion,determinant in matrix of chiral compound,electronic circular dichroism and vibrational circular dichroism.The stereogenic centers can be determined by comparing the theoretical values with the experimental data.Until now,it has become a popular way by using two or more theoretical methods in absolute configuration determination.On the other hand,it is a key and popular method to use a simplified model to replace a complex chiral compound in various calculations.This review analyzed the fundamental science and introduced a new concept of “conformer pair” for the first time.