Comparison of the Electronic and Vibrational Optical Activity of a Europium(III) Complex

The geometry and the electronic structure of chiral lanthanide(III) complexes are traditionally probed by electronic methods, such as circularly polarised luminescence (CPL) and electronic circular dichroism (ECD) spectroscopy. The vibrational phenomena are much weaker. In the present study, however, significant enhancements of vibrational circular dichroism (VCD) and Raman optical activity (ROA) spectral intensities were observed during the formation of a chiral bipyridine–Eu^III complex. The ten‐fold enhancement of the vibrational absorption and VCD intensities was explained by a charge‐transfer process and the dominant effect of the nitrate ion on the spectra. A much larger enhancement of the ROA and Raman intensities and a hundred‐fold increase of the circular intensity difference (CID) ratio were explained by the resonance of the λ=532 nm laser light with the ⁷F₀ → ⁵D₀ transitions. This phenomenon is combined with a chirality transfer, and mixing of the Raman and luminescence effects involving low‐energy ⁷F states of europium. The results thus indicate that the vibrational optical activity (VOA) may be a very sensitive tool for chirality detection and probing of the electronic structure of Eu^III and other coordination compounds.     

Sol-gel phase transition of brucine-appended porphyrin gelator: a study by vibrational circular dichroism spectroscopy

A novel approach to study the sol-gel phase transition of a brucine–porphyrin based gelator, which uses vibrational circular dichroism (VCD) spectroscopy, is described. The gelation process leading to highly ordered chiral supramolecular assemblies was investigated in various solvents at the different temperatures and concentrations. The VCD spectra sensitively reveal the specific parts of molecule whose configuration is influenced by a sol-gel phase transition and chiral supramolecular aggregation and therefore indicate the parts of the molecule responsible for the chiral self-assembly formation. Temperature stability of the organogel studied is discussed on the basis of the VCD and IR absorption spectra. The scanning electron microscopy was used to visualize the structure of brucine–porphyrin conjugate in the gel phase.     

Preferred-handed helical conformation in organic–inorganic hybrid block copolymers with well-controlled stereoregularity

A novel block copolymer containing polyhedral oligomeric silsesquioxanes (POSS) features a well-controlled stereoregularity, that is, isotactic polymethacrylate-functionalized POSS-b-polymethyl methacrylate (it-PMAPOSS-b-PMMA), was prepared via controlled-anionic polymerization. The stereoregularity of each segment in the it-PMAPOSS-b-PMMA is evaluated using nuclear magnetic resonance (NMR) spectroscopy, which reveals an isotactic configuration in both the PMAPOSS and PMMA segments. The secondary structure of it-PMAPOSS-b-PMMA in a mixture with a small chiral dopant is clarified with electronic circular dichroism and vibrational circular dichroism measurements. By adding a chiral dopant, a controlled preferential helical conformation of the unilateral segment in achiral it-PMAPOSS-b-PMMA is achieved.     

应用电子圆二色光谱方法确定手性金属配合物的绝对构型

与电子能级跃迁相关的电子圆二色(ECD)光谱因其研究对象宽泛,与涉及振动能级的振动圆二色(VCD)光谱互补,已成为应用于手性立体化学研究的集成手性光谱的主流表征手段。本文概述了确定手性金属配合物绝对构型的三种主要方法,详细介绍了ECD光谱法在确定手性金属配合物绝对构型中的应用,其中着重强调了激子手性方法,并对集成手性光谱学未来的发展趋势做出了展望。     

Fluorescence detected circular dichroism (FDCD) for supramolecular host–guest complexes

Fluorescence-detected circular dichroism (FDCD) spectroscopy is applied for the first time to supramolecular host–guest and host–protein systems and compared to the more known electronic circular dichroism (ECD). We find that FDCD can be an excellent choice for common supramolecular applications, e.g. for the detection and chirality sensing of chiral organic analytes, as well as for reaction monitoring. Our comprehensive investigations demonstrate that FDCD can be conducted in favorable circumstances at much lower concentrations than ECD measurements, even in chromophoric and auto-emissive biofluids such as blood serum, overcoming the sensitivity limitation of absorbance-based chiroptical spectroscopy. Besides, the combined use of FDCD and ECD can provide additional valuable information about the system, e.g. the chemical identity of an analyte or hidden aggregation phenomena. We believe that simultaneous FDCD- and ECD-based chiroptical characterization of emissive supramolecular systems will be of general benefit for characterizing fluorescent, chiral supramolecular systems due to the higher information content obtained by their combined use.

Fluorescence-detected circular dichroism (FDCD) spectroscopy is applied for the first time to supramolecular host–guest and host–protein systems and compared to the more known electronic circular dichroism (ECD).     

Molecular origin for helical winding of fibrils formed by perfluorinated gelators

A chiral low-molecular weight gelator, N,N'-diperfluoroheptanoyl-1,2(R,R)- or -1,2(S,S)-diaminocyclohexane, was prepared to form a gel of acetonitrile. The conformation of the gelator in fibrils was determined by vibrational circular dichroism spectra, providing a molecular model for self-assembly in a helical fibril.     

Synthesis and Stereochemical Assignment of Crypto‐Optically Active 2H6‐Neopentane

The determination of the absolute configuration of chiral molecules is at the heart of asymmetric synthesis. Here we probe the spectroscopic limits for chiral discrimination with NMR spectroscopy in chiral aligned media and with vibrational circular dichroism spectroscopy of the sixfold‐deuterated chiral neopentane. The study of this compound presents formidable challenges since its stereogenicity is only due to small mass differences. For this purpose, we selectively prepared both enantiomers of ²H₆‐ 1 through a concise synthesis utilizing multifunctional intermediates. While NMR spectroscopy in chiral aligned media could be used to characterize the precursors to ²H₆‐ 1 , the final assignment could only be accomplished with VCD spectroscopy, despite the fleetingly small dichroic properties of 1 . Both enantiomers were assigned by matching the VCD spectra with those computed with density functional theory.     

Chiral benzimidazole-derived mono azacrowns: synthesis and enantiomer recognition studies with chiral amines and their ammonium salts

Benzimidazole fused chiral mono aza-15-crown-5 2, was obtained in a single step from (S)-(?)-2-(α-hydroxyethyl) benzimidazole 1. This new class of aza-crown has a unique structure with the chiral unit being held in a stable conformation due to adjacent benzimidazole ring contributing to its stereodiscrimination ability. The interactions between the host aza-crown and enantiomerically pure amine guests in ionic and neutral forms exhibited the enantio-discrimination ability. The preliminary evaluation of the chiral sensing was monitored using ¹H NMR and circular dichroism (CD) analysis of the complexes at their molar equivalence. The binding parameters were determined using electronic absorption spectroscopy.     

Electronic Structure and Circular Dichroism of Natural Alboatisins Isolated from Aerial Parts of Isodon Albopilosus: DFT and TDDFT Study

The stable conformations of a series of bioactive molecules, (?)-alboatisins A?C, are identified via Monte Carlo searching with the MMFF94 molecular mechanics force field. Then, the optical rotation (OR) values, vibrational circular dichroism (VCD), and electronic circular dichroism (ECD) spectra were calculated using the gradient-corrected density functional theory method. The vibrational and transition modes of molecular chirality were explored in terms of their microscopic origin. The calculated specific rotations are in agreement with the experimental values. From the OR analysis, it was concluded that optical rotation values areregulated by hydroxyl substitution. Vibrations occurring on the chiral skeleton may cause strong absorption in VCD spectra; VCD spectra are thus the spectral response to deformation vibrations on the chiral carbon skeleton. The lowest-energy negative Cotton effect is caused by σ→π^* transition. Frontier molecular orbital analysis showed that strong ECD absorptions are produced when the dominant transition on the chiral skeleton is asymmetric; ECD spectra show the result of transitions lacking asymmetry on the chiral skeleton.     

Entropy driven binding of the alkaloid chelerythrine to polyadenylic acid leads to spontaneous self-assembled structure formation

The binding thermodynamics and interaction of the putative anticancer alkaloid chelerythrine with polyadenylic acid were investigated by isothermal titration calorimetry, absorption and fluorescence spectroscopy, circular dichroism, differential scanning calorimetry and thermal melting experiments. The equilibrium binding constant was evaluated to be of the order of 10⁷ M⁻¹. Strong positive entropic and favorable enthalpic contributions to the binding were revealed. The binding affinity was enhanced within (10 to 100) mM Na⁺ concentration. Circular dichroism spectra confirmed that the increase in entropy change was caused by a strong conformational change in the RNA polynucleotide. Absorption and circular dichroism melting studies revealed that chelerythrine binding induced self-assembled duplex structure formation in poly(A) molecules resulting in a cooperative melting profile. This was further confirmed from differential scanning calorimetry data. The intercalation binding of the alkaloid involved strong energy transfer from the polynucleotide bases to the bound alkaloid molecules. The remarkably high entropy driven binding of the alkaloid induced spontaneous self-assembled structure formation in poly(A) and the associated binding affinity is the highest so far reported for a small molecule binding to poly(A).     

Preparation of cruciferous phytoalexin related metabolites, (−)-dioxibrassinin and (−)-3-cyanomethyl-3-hydroxyoxindole, and determination of their absolute configurations by vibrational circular dichroism (VCD)

Cruciferous phytoalexin related metabolites, (−)-dioxibrassinin (1) and (−)-3-cyanomethyl-3-hydroxyoxindole (2) were prepared from isatin as racemates and were resolved by chiral HPLC. Their absolute configurations were determined by the new chiroptical technique, vibrational circular dichroism (VCD), as well as by the conventional electronic circular dichroism (ECD). It is concluded that the absolute configurations of the naturally occurring (−)-1 and (−)-2 are both S.     

Absolute configuration assignment of caffeic acid ester derivatives from Tithonia diversifolia by vibrational circular dichroism: the pitfalls of deuteration

Recently, it was observed that infrared (IR) and vibrational circular dichroism (VCD) calculations including deuterated hydroxyl groups in phenolic and saccharide moieties improved significantly the agreement with experimental data obtained in methanol-d₄. In the present study, the relative and absolute configurations of three methanol-soluble caffeic acid ester derivatives 1–3, isolated from Tithonia diversifolia, were established by a combined use of experimental and calculated ¹³C NMR chemical shifts, as well as electronic circular dichroism (ECD) and VCD spectroscopies. Interestingly, the attempt to reproduce the deuteration pattern arising from possible isotopic exchange in methanol-d₄ solution led to nearly mirror image calculated VCD spectra for 1 when compared to the non-deuterated molecule with the same absolute configuration. This latter fact can potentially lead to absolute configuration misassignments. A closer inspection of the vibrational chiroptical properties of 1 revealed that the deuteration status of the tertiary hydroxyl group at C-2 is critical for the correct reproduction of experimental VCD data in protic solvents. Therefore, in the case of stereochemical analysis of polar chiral natural product molecules, a combination of VCD and ECD is recommended.     

Vibrational circular dichroism spectroscopy of chiral pheromones: frontalin (1,5-dimethyl-6,8-dioxabicyclo[3.2.1]octane)

Ab initio density functional theory (DFT) is used to predict the vibrational absorption and circular dichroism spectra of the insect pheromone 1,5-dimethyl-6,8-dioxabicyclo[3.2.1]octane: frontalin. Excellent agreement with experimental spectra is obtained for the structure in which the six-membered ring is in a chair conformation and the seven-membered ring is in a boat conformation. Vibrational circular dichroism (VCD) intensities, predicted on the basis of the previously determined absolute configuration, are in excellent agreement with experiment. We conclude that VCD spectroscopy, in combination with ab initio DFT, is now an efficient tool for determining the absolute configuration and/or conformation of chiral organic molecules, including pheromones.     

Clickable 9-azido-(9-deoxy)-Cinchona alkaloids: synthesis and conformation

The synthesis and conformational preferences of 9-azido-(9-deoxy)-Cinchona alkaloids constituting a novel class of Cinchona alkaloid derivatives of both natural and 9-epi configurations are described. One and two-step preparative syntheses of 9-azido-(9-deoxy)-Cinchona alkaloids have been developed, allowing for their easy access on a multigram scale. The stereochemical integrity of these azides has been confirmed from their circular dichroism and specific rotation data. The conformations of the 9-azido Cinchona alkaloids, deduced from both ¹H NMR and DFT calculations, show that this class of Cinchona derivatives largely reflect the conformational preferences of the corresponding Cinchona bases; this strategy, therefore, offers a defined chiral and clickable scaffold.     

Isolation and absolute configuration determination of alkaloids from Pandanus amaryllifolius

Seven new alkaloids belonging to three typical classes, isolated from an ethanolic extract of Pandanus amaryllifolius, were applied to establish the models in structural elucidation. The first type [pandanusines A and B (1 and 2)] was applied to alkaloids with a diazaspirocyclic ring system. The absolute stereochemistry of aminal carbon is determined by analysis of J-based configuration analysis and circular dichroism spectroscopy, which has never been revealed before. The second type [pandalizines C–E (3–5)], the stereochemistry of unusual indolizinone with chiral hydroxyl substitutions were determined by circular dichroism spectroscopy and vibrational circular dichroism experiments. The last type [norpandamarilactonines C and D (6 and 7)], a comparing model in determination of diastereomers of pyrrolidinyl α,β-unsaturated γ-lactone alkaloids was established. Our study provides solutions for a challenging subject in stereochemistry determination for three different types of Pandanus alkaloids.     

New chiral discotics with helical organization of the mesophase—liquid crystalline derivatives of dibenzotetraaza[14]annulene

Two optically pure derivatives of dibenzotetraaza[14]annulene, bearing four (S)- or (R)- 3,7-dimethyloctoxy peripheral chiral tails, respectively, and two hydroxybenzoyl meso substituents were synthesized using a convergent multi-step route. The structure of the products was determined by ¹H and ¹³C NMR spectroscopy, ESI-MS, and elemental analysis. The mesomorphic behavior of the two chiral compounds, deciphered by differential scanning calorimetry (DSC), small-angle X-ray diffractometry (SA-XRD), and polarizing optical microscopy (POM) investigations, revealed the induction of two lamello-columnar phases, i.e., columnar stacks confined in smectic layers, whose columns may be arranged either according to the pg rectangular planar symmetry (for the low-temperature phase) or without registry between vicinal layers (for the high-temperature mesophase). Evidence of a helical organization of the molecules in the mesophases was obtained using a combination of electronic circular dichroism (ECD) and SA-XRD results, Molecular Dynamics simulations and quantum-chemical calculations.     

Theoretical and experimental study of the absolute configuration of helical structure of (2R,3S)-Rubiginone A2 analog

A novel analogue of (2R,3S)-Rubiginone A₂ was synthesized as a chiral helical model compound via an eight-step procedure (2.7% overall yield). Quantum methods, such as density functional theory (DFT) at different basis sets of 6-311+(d), 6-311++G(2d,p), were used to compute its optical rotation and electronic circular dichroism at the B3LYP/6-311++G(2d,p) level in the gas phase and in solution using PCM model, respectively. UV corrections were performed in electronic circular dichroism (ECD) simulations to match the experimental ECD well. The suitable computational methods, e.g., B3LYP/6-311++G(2d,p)//B3LYP/6-311++G(2d,p) in the gas phase using zero-point energy in Boltzmann statistics, were found and suggested for optical rotation and circular dichroism computations that can be used for absolute configuration determination of chiral helical compounds.     

Towards an Observation of Active Conformations in Asymmetric Catalysis: Interaction‐Induced Conformational Preferences of a Chiral Thiourea Model Compound

The observation of the active species is the goal of most spectroscopic investigations on enantioselective organocatalysts in solution. Although NMR spectroscopy is widely applied, it has low sensitivity for conformational changes or the chiral nature of the interactions. In the present work, we exemplify the use of vibrational circular dichroism (VCD) spectroscopy for the characterization of a chiral thiourea model compound in nonpolar and polar solvents, as well as for a detailed analysis of its interaction with a model reactant. We discuss solvent‐induced conformational changes of the thiourea, and provide evidence for an unexpected binding topology between the thiourea and an acetate anion. The results clearly showcase the possibilities offered by using VCD spectroscopy in the characterization of chiral organocatalysts.     

Laser Mass Spectrometry with Circularly Polarized Light: Circular Dichroism of Cold Molecules in a Supersonic Gas Beam

An experiment on chiral molecules that combines circular dichroism (CD) spectroscopy, mass‐selective detection by laser mass spectrometry (MS), and cooling of molecules by using a supersonic beam is presented. The combination of the former two techniques (CD–laser‐MS) is a new method to investigate chiral molecules and is now used by several research groups. Cooling in a supersonic beam supplies a substantial increase in spectroscopic resolution, a feature that has not yet been used in CD spectroscopy. In the experiments reported herein, a large variation in the electronic CD of carbonyl 3‐methylcyclopentanone was observed depending on the excited vibrational modes in the n→π* transition. This finding should be of interest for the detection of chiral molecules and for the theoretical understanding of the CD of vibronic bands. It is expected that this effect will show up in other chiral carbonyls because the n→π* transition is typical for the carbonyl group.     

Homochiral Supramolecular M2L4 Cages by High‐Fidelity Self‐Sorting of Chiral Ligands

A 1,1′‐binaphthyl‐based bis(pyridine) ligand ( 1 ) was prepared in racemic and enantiomerically pure form to study the formation of [Pd₂( 1 )₄] complexes upon coordination to palladium(II) ions with regard to the degree of chiral self‐sorting. The self‐assembly process proceeds in a highly selective narcissistic self‐recognition manner to give only homochiral supramolecular M₂L₄ cages, which were characterized by ESI‐MS, NMR, and electronic circular dichroism (ECD) spectroscopy, as well as by single‐crystal XRD analysis.