Chiral Molecular Structure Research Articles

Laser-induced electron diffraction: Imaging of a single gas-phase molecular structure with one of its own electrons.

Among the many methods to image molecular structure, laser-induced electron diffraction (LIED) can image a single gas-phase molecule by locating all of a molecule's atoms in space and time. The method is based on attosecond electron recollision driven by a laser field and can reach attosecond temporal resolution. Implementation with a mid-IR laser and cold-target recoil ion-momentum spectroscopy, single molecules are measured with picometer resolution due to the keV electron impact energy without ensemble averaging or the need for molecular orientation. Nowadays, the method has evolved to detect single complex and chiral molecular structures in 3D. The review will touch on the various methods to discuss the implementations of LIED toward single-molecule imaging and complement the discussions with noteworthy experimental findings in the field.

Expression of chiral molecular and supramolecular structure on enantioselective catalytic activity

Understanding the structure-function relationships encoded on chiral catalysts is important for investigating the fundamental principles of catalytic enantioselectivity. Herein, the synthesis and self-assembly of naphthalene substituted bis-l/d-histidine amphiphiles (bis-l/d-NapHis) in DMF/water solution mixture is reported. The resulting supramolecular assemblies featuring well-defined P/M nanoribbons (NRs). With combination of the (P/M)-NR and metal ion catalytic centers (Mn+ = Co2+, Cu2+, Fe3+), the (P)-NR-Mn+ as chiral supramolecular catalysts show catalytic preference to 3,4-dihydroxy-S-phenylalanine (S-DOPA) oxidation while the (M)-NR-Mn+ show enantioselective bias to R-DOPA oxidation. In contrast, their monomeric counterparts bis-l/d-NapHis-Mn+ display an inverse and dramatically lower catalytic selectivity in the R/S-DOPA oxidation. Among them, the Co2+-coordinated supramolecular nanostructures show the highest catalytic efficiency and enantioselectivity (select factor up to 2.70), while the Fe3+-coordinated monomeric ones show nearly racemic products. Analysis of the kinetic results suggests that the synergistic effect between metal ions and the chiral supramolecular NRs can significantly regulate the enantioselective catalytic activity, while the metal ion-mediated monomeric bis-l/d-NapHis were less active. The studies on association constants and activation energies reveal the difference in catalytic efficiency and enantioselectivity resulting from the different energy barriers and binding affinities existed between the chiral molecular/supramolecular structures and R/S-DOPA enantiomers. This work clarifies the correlation between chiral molecular/supramolecular structures and enantioselective catalytic activity, shedding new light on the rational design of chiral catalysts with outstanding enantioselectivity.

Chiral organic molecular structures supported by planar surfaces.

We employ the molecular dynamics simulations to study the dynamics of acetanilide (ACN) molecules placed on a flat surface of planar multilayer hexagonal boron nitride. We demonstrate that the ACN molecules, known to be achiral in the three-dimensional space, become chiral after being placed on the substrate. Homochirality of the ACN molecules leads to stable secondary structures stabilized by hydrogen bonds between peptide groups of the molecules. By employing molecular dynamics simulations, we reveal that the structure of the resulting hydrogen-bond chains depends on the isomeric composition of the molecules. If all molecules are homochiral (i.e., with only one isomer being present), they form secondary structures (chains of hydrogen bonds in the shapes of arcs, circles, and spirals). If the molecules at the substrate form a racemic mixture, then no regular secondary structures appear, and only curvilinear chains of hydrogen bonds of random shapes emerge. A hydrogen-bond chain can form a zigzag array only if it has an alternation of isomers. Such chains can create two-dimensional (2D) regular lattices or 2D crystals. The melting scenarios of such 2D crystals depend on density of its coverage of the substrate. At 25% coverage, melting occurs continuously in the temperature interval 295-365K. For a complete coverage, melting occurs at 415-470 K due to a shift of 11% of all molecules into the second layer of the substrate.

Interplay of structural chirality, electron spin and topological orbital in chiral molecular spin valves

Chirality has been a property of central importance in physics, chemistry and biology for more than a century. Recently, electrons were found to become spin polarized after transmitting through chiral molecules, crystals, and their hybrids. This phenomenon, called chirality-induced spin selectivity (CISS), presents broad application potentials and far-reaching fundamental implications involving intricate interplays among structural chirality, topological states, and electronic spin and orbitals. However, the microscopic picture of how chiral geometry influences electronic spin remains elusive, given the negligible spin-orbit coupling (SOC) in organic molecules. In this work, we address this issue via a direct comparison of magnetoconductance (MC) measurements on magnetic semiconductor-based chiral molecular spin valves with normal metal electrodes of contrasting SOC strengths. The experiment reveals that a heavy-metal electrode provides SOC to convert the orbital polarization induced by the chiral molecular structure to spin polarization. Our results illustrate the essential role of SOC in the metal electrode for the CISS spin valve effect. A tunneling model with a magnetochiral modulation of the potential barrier is shown to quantitatively account for the unusual transport behavior.

Cobalt-Induced Phase Transformation of Ni3Ga4 Generates Chiral Intermetallic Co3Ni3Ga8

The scientific community has found immense difficulty to focus on the generation of chiral intermetallics compared to the chiral molecular structure, probably due to the technical difficulty in producing them as no general controlled protocol is available. Herein, using a conventional metal flux technique, we have discovered a new ternary intermetallic Co3Ni3Ga8, substituting Co at the Ni sublattice in a highly symmetric Ni3Ga4 (Ia3̅d). Co3Ni3Ga8 crystallizes in the I4132 space group, a Sohncke type, and can host the chiral structure. To the best of our knowledge, this is the first report of a ternary intermetallic crystallizing in this space group. The chiral structure of Co3Ni3Ga8 is comprehensively mapped by various techniques such as single-crystal X-ray diffraction (XRD), synchrotron powder XRD, X-ray absorption spectroscopy (XAS), scanning transmission electron microscopy (STEM) and theoretically studied using density functional theory. The discovery of this chiral compound can inspire the researchers to design hidden ternary chiral intermetallics to study the exotic electrical and magnetic properties.

Bright Organic Mechanoluminescence and Remarkable Mechanofluorochromism from Circularly Polarized TADF Enantiomers with Aggregation-Induced Emission Properties.

The development of circularly polarized thermally activated delayed fluorescence (CP-TADF) luminogens with stimuli-response characteristics remains challenging. Herein, a pair of organic enantiomers, S-CzTA and R-CzTA, with aggregation-induced emission properties, have been successfully developed by introducing chiral 1,2,3,4-tetrahydronaphthalene and carbazole to phthalimide. They present CP-TADF properties in toluene solutions, giving dissymmetric factors of 0.84×10-3 and -1.03×10-3 , respectively. In the crystalline state, both S-CzTA and R-CzTA can emit intense blue TADF and produce very bright sky-blue mechanoluminescence (ML) and remarkable mechanofluorochromism (MFC) under the stimuli of mechanical force. Single-crystal analysis and theoretical calculation results suggest that their ML activities are probably associated with their chiral and polar molecular structures and unique non-centrosymmetric molecular packing modes. Furthermore, the MFC properties of the enantiomers likely originate from the destruction of crystal structure, leading to the planarization of molecular conformation. This work may provide helpful guidance for developing new CP-TADF materials with force-stimuli-responsive properties.

Stereoisomerism in Tetrametallic Propeller‐Like Complexes: A Solid‐State and Solution NMR Study on a Tetragallium(III) Derivative

AbstractTetragallium(III) complex in [Ga4(L4‐Py)2(dpm)6] ⋅ EtOH, with H3L4‐Py=2‐(hydroxymethyl)‐2‐(pyridin‐4‐yl)propane‐1,3‐diol and Hdpm=dipivaloylmethane, was investigated as a diamagnetic analogue of tetrametallic, propeller‐like single‐molecule magnets (SMMs). The chiral molecular structure partitions the six CH2 protons of each tripodal (L4‐Py)3− ligand into two diastereotopic sets. The two signals were clearly detected by 1H NMR spectroscopy in C6D6, proving that Λ and Δ enantiomers interconvert slowly over NMR timescale. Density functional theory calculations provided quantitative agreement with the observed values of chemical shifts and scalar coupling constants across both geminal and long‐range interaction pathways. The solid‐state structure suggests the occurrence of a lower symmetry stereoisomer (27 mol%), which was clearly identified in the NMR spectra. Since high spin Fe3+ forms distinctly more inert complexes than Ga3+, comparable or greater configurational stability is expected for the isostructural FeIII4, FeIII3CrIII, and FeIII3VIII SMMs, which are difficult to investigate by solution NMR because of the strong paramagnetism.

Chiral Molecular Structure Determination for a Desired Compound Just from Its Molecular Formula and Vibrational Optical Activity Spectra.

A novel proof-of-concept model for chiral molecular structure determination using just the molecular formula and vibrational optical activity (VOA) spectra is presented. To verify this concept, the molecular formula of a desired compound is used to generate all possible chiral structural isomers and their VOA spectra are predicted. The similarity analyses of predicted VOA spectra were then carried out in two different ways: (a) similarity between VOA spectrum of one structural isomer with those of the rest, referred to as cross-correlations; (b) similarity between VOA spectra of all chiral structural isomers with the experimental VOA spectra of the desired compound. Three different molecular formulae, C4H8O, C3H5ClO, and C6H10O, and their chiral structural isomers (6, 9, and 75 respectively), were investigated. In each case, the correct chiral molecular structure of the desired compound was identified without ambiguity. Cross-correlation analysis revealed the uniqueness of VOA spectra in deducing the chiral molecular structure solely from its molecular formula. Different chiral structural isomers associated with the molecular formula CH3NO2 were also found to have no significant cross-correlations between their VOA spectra, opening a pathway to detect and identify the elusive chiral N-hydroxyoxaziridine from its VOA spectra.

A versatile messenger for chirality communication: asymmetric silica framework

Asymmetric tetrahedral carbon is the basic structural unit of many organic compounds in life and its molecular chirality plays a key role in regulating biological functions. Silica (SiO2) is highly earth abundant and its basic unit is also the tetrahedral form of SiO4. However, much less attention has been paid to the molecular-scale chirality of SiO2 frameworks with repeating SiO4 units because it is challenging to enantioselectively control the molecular structures of SiO2. Research into the chiral molecular structures of SiO2 deserves to be a significant topic for understanding widespread chiral phenomena and for exploring the chiral properties hidden in inorganic matter. This review highlights the asymmetric synthesis strategies that endow SiO2 with chirality transferred from asymmetric carbon at the molecular scale. The chirality transfer ability of SiO2 is also demonstrated for the construction of various inorganic and/or organic chiral materials with a wide range of applications in asymmetric synthesis, circularly polarized luminescence and Raman scattering-based chiral recognition.

Vibrational origin of exchange splitting and ”chiral-induced spin selectivity

Electron exchange and correlations emerging from the coupling between ionic vibrations and electrons are addressed. Spin-dependent electron-phonon coupling originates from the spin-orbit interaction, and it is shown that such electron-phonon coupling introduces exchange splitting between the spin channels in the structure. By application of these results to a model for a chiral molecular structure mounted between metallic leads, the chirality induced spin selectivity is found to become several tens of percents using experimentally feasible parameters.

Helicity Control in the Aggregation of Achiral Squaraine Dyes in Solution and Thin Films.

Squaraine dyes are well known for their strong absorption in the visible regime. Reports on chiral squaraine dyes are, however, scarce. To address this gap, we here report two novel chiral squaraine dyes and their achiral counterparts. The presented dyes are aggregated in solution and in thin films. A detailed chiroptical study shows that thin films formed by co‐assembling the chiral dye with its achiral counterpart exhibit exceptional photophysical properties. The circular dichroism (CD) of the co‐assembled structures reaches a maximum when just 25 % of the chiral dye are present in the mixture. The solid structures with the highest relative CD effect are achieved when the chiral dye is used solely as a director, rather than the structural component. The chiroptical data are further supported by selected spin‐filtering measurements using mc‐AFM. These findings provide a promising platform for investigating the relationship between the dissymmetry of a supramolecular structure and emerging material properties rather than a comparison between a chiral molecular structure and an achiral counterpart.

Nanophotonic Platforms for Chiral Sensing and Separation.

Chirality in Nature can be found across all length scales, from the subatomic to the galactic. At the molecular scale, the spatial dissymmetry in the atomic arrangements of pairs of mirror-image molecules, known as enantiomers, gives rise to fascinating and often critical differences in chemical and physical properties. With increasing hierarchical complexity, protein function, cell communication, and organism health rely on enantioselective interactions between molecules with selective handedness. For example, neurodegenerative and neuropsychiatric disorders including Alzheimer's and Parkinson's diseases have been linked to distortion of chiral-molecular structure. Moreover, d-amino acids have become increasingly recognized as potential biomarkers, necessitating comprehensive analytical methods for diagnosis that are capable of distinguishing l- from d-forms and quantifying trace concentrations of d-amino acids. Correspondingly, many pharmaceuticals and agrochemicals consist of chiral molecules that target particular enantioselective pathways. Yet, despite the importance of molecular chirality, it remains challenging to sense and to separate chiral compounds. Chiral-optical spectroscopies are designed to analyze the purity of chiral samples, but they are often insensitive to the trace enantiomeric excess that might be present in a patient sample, such as blood, urine, or sputum, or pharmaceutical product. Similarly, existing separation schemes to enable enantiopure solutions of chiral products are inefficient or costly. Consequently, most pharmaceuticals or agrochemicals are sold as racemic mixtures, with reduced efficacy and potential deleterious impacts.Recent advances in nanophotonics lay the foundation toward highly sensitive and efficient chiral detection and separation methods. In this Account, we highlight our group's effort to leverage nanoscale chiral light-matter interactions to detect, characterize, and separate enantiomers, potentially down to the single molecule level. Notably, certain resonant nanostructures can significantly enhance circular dichroism for improved chiral sensing and spectroscopy as well as high-yield enantioselective photochemistry. We first describe how achiral metallic and dielectric nanostructures can be utilized to increase the local optical chirality density by engineering the coupling between electric and magnetic optical resonances. While plasmonic nanoparticles locally enhance the optical chirality density, high-index dielectric nanoparticles can enable large-volume and uniform-sign enhancements in the optical chirality density. By overlapping these electric and magnetic resonances, local chiral fields can be enhanced by several orders of magnitude. We show how these design rules can enable high-yield enantioselective photochemistry and project a 2000-fold improvement in the yield of a photoionization reaction. Next, we discuss how optical forces can enable selective manipulation and separation of enantiomers. We describe the design of low-power enantioselective optical tweezers with the ability to trap sub-10 nm dielectric particles. We also characterize their chiral-optical forces with high spatial and force resolution using combined optical and atomic force microscopy. These optical tweezers exhibit an enantioselective optical force contrast exceeding 10 pN, enabling selective attraction or repulsion of enantiomers based on the illumination polarization. Finally, we discuss future challenges and opportunities spanning fundamental research to technology translation. Disease detection in the clinic as well as pharmaceutical and agrochemical industrial applications requiring large-scale, high-throughput production will gain particular benefit from the simplicity and relative low cost that nanophotonic platforms promise.

Dissymmetry Factor Spectral Analysis Can Provide Useful Diastereomer Discrimination: Chiral Molecular Structure of an Analogue of (-)-Crispine A.

(1R,10bR)-1′-((R)-1,2-Dihydroxyethyl)-1-hydroxy-8,9-dimethoxy1,5,6,10b-tetrahydropyrrolo [2,1-a]isoquinolin-3(2H)-one, an analogue of (−)-crispine A, with three stereogenic centers is synthesized and its absolute configuration (AC) established using the combined information derived from the synthetic scheme and single crystal X-ray diffraction data. The experimental chiroptical spectra (namely, optical rotatory dispersion (ORD), electronic circular dichroism (ECD), and vibrational circular dichroism (VCD)) and the corresponding quantum chemical (QC) predicted spectra for all diastereomers are used to evaluate the AC. The AC of the synthesized compound could be correctly established using any one of the three chiroptical spectroscopic methods (ORD, ECD, or VCD) when the relative configuration is constrained to be that derived from X-ray data or when the ACs of two of the chiral centers are constrained to be those derived from the synthetic scheme. In the absence of this outside information, the QC predicted ORD, ECD, and VCD for incorrect diastereomers are also found to satisfactorily reproduce the corresponding experimental spectra. Nevertheless, incorrect diastereomers could be eliminated when combined electronic dissymmetry factor (EDF) and vibrational dissymmetry factor (VDF) spectral analyses are included, leaving the correct diastereomer as the sole choice. Thus, the combined EDF and VDF spectral analysis is seen to be a helpful diastereomer discrimination tool.

Chiral Molecular Structures of Substituted Indans: Ring Puckering, Rotatable Substituents, and Vibrational Circular Dichroism.

The chiral molecular structures of four different substituted indans, namely, (S)-1-methylindan, (R)-1-methylindan-1-d, (R)-1-aminoindan, and (S)-1-indanol, were investigated using experimental vibrational absorption and vibrational circular dichroism spectra and corresponding spectra predicted using quantum chemical (QC) calculations. All of these molecules possess two ring puckering conformations, with ring puckering leading to the pseudoequatorial substituent being approximately four times more abundant over that leading to the pseudoaxial substituent. The amino group in 1-aminoindan has three conformations arising from the rotation of NH2 group, for each ring puckering conformation, resulting in a total of six conformations. Whereas 1-indanol in the nonhydrogen-bonding solvent CCl4 also has six conformations similar to those of 1-aminoindan, 1-indanol in the hydrogen-bonding solvent DMSO-d6 adopts numerous conformations, of which 30 conformers are considered to have at least ∼1% or more population. In DMSO solution, ring puckering leading to pseudoequatorial substituent accounts for 77% population and 23% for pseudoaxial substituent. The QC spectra predicted for the geometry optimized conformers are found to be in excellent quantitative agreement with corresponding experimental spectra in all of the molecules considered. The procedures suggested in this work are hoped to provide successful pathways for future chiral molecular structural analyses.

Chiral Stationary Phases and their Relationship with Enantiomer Structures in Enantioseparation Research of Analytical Laboratory

Chiral stationary phases (CSPs) and molecular structure of enantiomers are two independent but related aspects in enantioseparation, which are discussed on the basis of the experimental data from the previous study. Two enantioseparation experiments are performed to illustrate the relationship between enantiomer structures and chiral stationary phases, one is the resolution of mandelic acid derivatives and the other is about prasugrel. Thermodynamic mechanism and theoretical study with computational chemistry method is helpful to understand the interactions of enantiomer and CSPs.

Determination of the Absolute Configurations of Chiral Drugs Using Chiroptical Spectroscopy.

Chiroptical spectroscopy has emerged as a promising tool for the determination of absolute configurations and predominant conformations of chiral molecules in academic laboratories. This promise has led to the adaption of chiroptical spectroscopic methods as valuable tools in chiral drug discovery research programs of the pharmaceutical industry. Most major pharmaceutical companies have invested in in-house chiroptical spectroscopy applications and reported successful outcomes. In the context of continuously increasing applications of chiroptical spectroscopy for chiral molecular structure determination, a review of recent developments and applications for chiral drugs is presented in this manuscript.

Communication: Probing the absolute configuration of chiral molecules at aqueous interfaces.

We demonstrate that the enantiomers of chiral macromolecules at an aqueous interface can be distinguished with monolayer sensitivity using heterodyne-detected vibrational sum-frequency generation (VSFG). We perform VSFG spectroscopy with a polarization combination that selectively probes chiral molecular structures. By using frequencies far detuned from electronic resonances, we probe the chiral macromolecular structures with high surface specificity. The phase of the sum-frequency light generated by the chiral molecules is determined using heterodyne detection. With this approach, we can distinguish right-handed and left-handed helical peptides at a water-air interface. We thus show that heterodyne-detected VSFG is sensitive to the absolute configuration of complex, interfacial macromolecules and has the potential to determine the absolute configuration of enantiomers at interfaces.

ChemInform Abstract: Comparison of Experimental and Calculated Chiroptical Spectra for Chiral Molecular Structure Determination

AbstractReview: 40 refs.

Comparison of Experimental and Calculated Chiroptical Spectra for Chiral Molecular Structure Determination

For three different chiroptical spectroscopic methods, namely, vibrational circular dichroism (VCD), electronic circular dichroism (ECD), and Raman optical activity (ROA), the measures of similarity of the experimental spectra to the corresponding spectra predicted using quantum chemical theories are summarized. In determining the absolute configuration and/or predominant conformations of chiral molecules, these similarity measures provide numerical estimates of agreement between experimental observations and theoretical predictions. Selected applications illustrating the similarity measures for absorption, circular dichroism, and corresponding dissymmetry factor (DF) spectra, in the case of VCD and ECD, and for Raman, ROA, and circular intensity differential (CID) spectra in the case of ROA, are presented. The analysis of similarity in DF or CID spectra is considered to be much more discerning and accurate than that in absorption (or Raman) and circular dichroism (or ROA) spectra, undertaken individually.

Photoswitchable molecular switches featuring both axial and tetrahedral chirality

In this study, we develop a kind of novel photoswitchable chiral azo switches bearing both axially chiral binaphthyl center and single tetrahedrally chiral center with different configurations. The influence of the configuration of the tetrahedrally chiral centers and the introduction of a rigid structure on the helical twisting power (HTP) of the chiral azo switch was addressed in detail. Our results demonstrate that the import of the tetrahedrally chiral center dramatically decreased the HTP of the axially chiral azo switch, while the rigid long core increased the HTP. According to a molecular simulation based on Gaussian03 calculations at the B3LYP/6-31G(d) level, both the molecular configuration and the molecular aspect ratio were found to be the key factors influencing the HTP of the chiral azo switch. Finally, we utilize the above chiral azo switch to fabricate a photo-addressed, flexible liquid crystal device. This work provides an insight into the relationship between the chiral effect and molecular structure of chiral switches and their potential applications for photonic and display fields.