Conventional Circular Dichroism Research Articles

Trace-Amount Detection of Chiral Molecules Based on Plasmonic Racemic Arrays Fabricated via Direct Laser Writing.

Superchiral fields, supported by chiral plasmonic structures, have shown outstanding performance for chiral molecule sensing via enhanced chiral light-matter interaction. However, this sensing capability cannot fully reveal the chiral origin of the molecules as the chiroptic response of the molecules is intertwined with the chiroptic response of the chiral plasmonic nanostructures, which can potentially be excluded by using a plasmonic racemic mixture. Such a plasmonic racemic mixture is not easily attainable, as it normally requires complex fabrication and expensive instrumentation, whose structural fineness is limited by the fabrication precision. Here, we demonstrate trace-amount chiral molecule detection with plasmonic racemic arrays fabricated by direct laser writing with vector beams, which is facile, cost-effective, and highly controllable. The racemic arrays present no inherent circular differential scattering but a large local superchiral field, which reflects the intrinsic chiral features of the chiral molecules. They are further applied to discriminate enantiomers of phenylalanine with a limit of detection (LOD) of 10.0 ± 2.8 μM, which is an order of magnitude smaller than the LOD of conventional circular dichroism spectroscopy. The strong local superchiral field provided by the plasmonic racemic arrays enlightens the design of a superior sensing platform, which holds promising applications for biomedical detection and enantioselective drug development.

Use of Synchrotron Radiation Circular Dichroism to Analyze the Interaction and Insertion of Proteins into Bacterial Outer Membrane Vesicles.

Circular dichroism (CD) is a spectroscopic technique commonly used for the analysis of proteins. Particularly, it allows the determination of protein secondary structure content in various media, including the membrane environment. In this chapter, we present how CD applications can be used to analyze the interaction of proteins with bacterial outer membrane vesicles (OMVs). Most CD studies characterizing the structure of proteins inserted into membranes rely on artificial lipid bilayers, mimicking natural membranes. Nevertheless, these artificial models lack the important features of the true membrane, especially for the outer membrane of Gram-negative bacteria. These features include lipid diversity, glycosylation, and asymmetry. Here, we show how to analyze the interactions of proteins, either integral or peripheral, with OMVs in solution and with supported membranes of OMVs, using conventional CD and orientated circular dichroism (OCD). We explain how to decipher the spectroscopic signals to obtain information on the molecular structure of the protein upon its interaction with an OMV and through its potential insertion into an OMV membrane.

Spatially Correlated Chirality in Chiral Two-Dimensional Perovskites Revealed by Second-Harmonic-Generation Circular Dichroism Microscopy.

Understanding the chiral mechanism of chiral hybrid perovskites is a prerequisite for developing relevant chiroptoelectronic applications. Although conventional circular dichroism (CD) spectroscopy can be used to characterize chirality in chiral perovskites, it has a low signal-to-noise ratio and can provide only information about macroscopic chirality. Herein, with the aim of revealing the microscopic chiral mechanism in chiral perovskites, we utilize a spacer cation alloying strategy to construct chiral two-dimensional perovskites. For the first time, we demonstrate second-harmonic-generation CD microarea imaging in chiral perovskite thin films to unveil their spatially correlated chirality. In combination with theoretical calculations, it is revealed that the spatially correlated chirality is caused by localized out-of-plane supramolecular orientations. This work will not only advance the understanding of the mechanism of chiroptical activity in chiral perovskites but also provide inspiration for the rational design and synthesis of perovskites for chirality-related nonlinear optoelectronic devices.

Theoretical and experimental analysis of circularly polarized luminescence spectrophotometers for artifact-free measurements using a single CCD camera

Circularly polarized luminescence (CPL) is a fast growing research field as a complementary chiroptical spectroscopy alternative to the conventional circular dichroism or in the quest of devices producing circularly polarized light for different applications. Because chiroptical signals are generally lower than 0.1%, conventional chiral spectroscopies rely on polarization time modulation requiring step-by-step wavelength scanning and a long acquisition time. High throughput controls motivated the development of CPL spectrophotometers using cameras as detectors and space polarization splitting. However, CPL measurements imposes careful precautions to minimize the numerous artifacts arising from experimental imperfections. Some previous work used complex calibration procedure to this end. Here we present a rigorous Mueller analysis of an instrument based on polarizations space splitting. We show that by using one camera and combining spatial and temporal separation through two switchable circular polarization encoding arms we can record accurate CPL spectra without the need of any calibration. The measurements robustness and their fast acquisition times are exemplified on different chiral emitters.

Adjuvant effect of mesoporous silica SBA-15 on anti-diphtheria and anti-tetanus humoral immune response

Routine immunization against diphtheria and tetanus has drastically reduced the incidence of these diseases worldwide. Anti-diphtheria/tetanus vaccine has in general aluminum salt as adjuvant in its formulation that can produce several adverse effects. There is a growing interest in developing new adjuvants. In this study, we evaluated the efficiency of SBA-15 as an adjuvant in subcutaneous immunization in mice with diphtheria (dANA) and tetanus (tANA) anatoxins as well as with the mixture of them (dtANA). The tANA molecules and their encapsulation in SBA-15 were characterized using Small-Angle X-ray Scattering (SAXS), Dynamical Light Scattering (DLS), Nitrogen Adsorption Isotherm (NAI), Conventional Circular Dichroism (CD)/Synchrotron Radiation Circular Dichroism (SRCD) Spectroscopy, and Tryptophan Fluorescence Spectroscopy (FS). The primary and secondary antibody response elicited by subcutaneous immunization of High (HIII) and Low (LIII) antibody responder mice with dANA, tANA, or dtANA encapsulated in the SBA-15 were determined. We demonstrated that SBA-15 increases the immunogenicity of dANA and tANA antigens, especially when administered in combination. We also verified that SBA-15 modulates the antibody response of LIII mice, turning them into high antibody responder. Thus, these results suggest that SBA-15 may be an effective adjuvant for different vaccine formulations.

Ultrathin Suspended Chiral Metasurfaces for Enantiodiscrimination (Adv. Mater. 37/2022)

Metasurfaces A self-aligned suspended chiral bilayer metasurface via single-step electron-beam lithography is reported by Tun Cao, Yan Jun Liu, and co-workers in article number 2203956. A huge optical chirality of 221° μm−1 is achieved by the free-standing metasurfaces with overall thickness of 100 nm. The bilayer metasurface demonstrates label-free discrimination of chiral molecules at zeptomole level, with sensitivity orders of magnitude larger than conventional circular dichroism spectroscopy.

Ultrathin Suspended Chiral Metasurfaces for Enantiodiscrimination.

Chiral metasurfaces can exhibit a strong circular dichroism, but it is limited by the complicated fabrication procedure and alignment errors. Here, a new type of self-aligned suspended chiral bilayer metasurface with only one-step electron beam lithography exposure is demonstrated. A significant optical chirality of 221°µm-1 can be realized using suspended metasurfaces with a thickness of 100nm. Furthermore, this study experimentally demonstrates that such a structure is capable of label-free discrimination of the chiral molecules at zeptomole level, exhibiting a much higher sensitivity (orders of magnitude) compared to the conventional circular dichroism spectroscopy. The fundamental principles for chiral sensing using molecules-metasurfaces interactions are explored. Benefiting from the giant chiroptical response, the proposed metadevice may offer promising applications for ultrathin circular polarizers, chiral molecular detectors, and asymmetry information processing.

Plasmonic Enhancement of Chiroptical Property in Enantiomers Using a Helical Array of Magnetoplasmonic Nanoparticles for Ultrasensitive Chiral Recognition.

Recognition of enantiomeric molecules is essential in pharmaceutical and biomedical applications. In this Article, a novel approach is introduced to monitor chiral molecules via a helical magnetic field (hB), where chiral-inactive magnetoplasmonic nanoparticles (MagPlas NPs, Ag@Fe3O4 core-shell NPs) are assembled into helical nanochain structures to be chiral-active. An in-house generator of hB-induced chiral NP assembly, that is, a plasmonic chirality enhancer (PCE), is newly fabricated to enhance the circular dichroism (CD) signals from chiral plasmonic interaction of the helical nanochain assembly with circularly polarized light, reaching a limit of detection (LOD) of 10-10 M, a 1000-fold enhancement as compared to that of conventional CD spectrometry. These enhancements were successfully observed from enantiomeric molecules, oligomers, polymers, and drugs. Computational simulation studies also proved that total chiroptical properties of helical plasmonic chains could be readily changed by modifying the chiral structure of the analytes. The proposed PCE has the potential to be used as an advanced tool for qualitative and quantitative recognition of chiral materials, enabling further application in pharmaceutical and biomedical sensing and imaging.

In Situ Monitored Vortex Fluidic-Mediated Protein Refolding/Unfolding Using an Aggregation-Induced Emission Bioprobe.

Protein folding is important for protein homeostasis/proteostasis in the human body. We have established the ability to manipulate protein unfolding/refolding for β-lactoglobulin using the induced mechanical energy in the thin film microfluidic vortex fluidic device (VFD) with monitoring as such using an aggregation-induced emission luminogen (AIEgen), TPE-MI. When denaturant (guanidine hydrochloride) is present with β-lactoglobulin, the VFD accelerates the denaturation reaction in a controlled way. Conversely, rapid renaturation of the unfolded protein occurs in the VFD in the absence of the denaturant. The novel TPE-MI reacts with exposed cysteine thiol when the protein unfolds, as established with an increase in fluorescence intensity. TPE-MI provides an easy and accurate way to monitor the protein folding, with comparable results established using conventional circular dichroism. The controlled VFD-mediated protein folding coupled with in situ bioprobe AIEgen monitoring is a viable methodology for studying the denaturing of proteins.

Circular dichroism spectroscopy and chiral sensing in optical fibers.

Chirality is a property of broken mirror symmetry and detecting the handedness of chiral material in small quantities is an important problem in biology and biochemistry. Here, we present a waveguide-based method to measure chirality and distinguish the enantiomers of molecules. A bi-isotropic core in an optical waveguide lifts the degeneracy of modes in a cylindrically symmetric structure. This modal degeneracy lifting is exploited to measure the chirality of the core. The proposed sensor can determine the value of the chirality parameter of the material under test and it can be utilized for various materials with nonzero chirality parameter in different frequency bands. This approach improves the circular dichroism (CD) response and outperforms conventional CD spectroscopy methods by increasing their differential output signal. To compare the results with conventional CD spectroscopy, the CD parameter is adapted to optical waveguides.

Total Angular Momentum Dichroism of the Terahertz Vortex Beams at the Antiferromagnetic Resonances.

Terahertz vortex beams with different superposition of the orbital angular momentum l=±1, ±2, ±3, and ±4 and spin angular momentum σ=±1 were used to study antiferromagnetic (AFM) resonances in TbFe_{3}(BO_{3})_{4} and Ni_{3}TeO_{6} single crystals. In both materials we observed a strong vortex beam dichroism for the AFM resonances that are split in external magnetic field. The magnitude of the vortex dichroism is comparable to that for conventional circular dichroism due to σ. The selection rules at the AFM resonances are governed by the total angular momentum of the vortex beam: j=σ+l. In particular, for l=±2, ±3, and ±4 the sign of l is shown to dominate over that for conventional circular polarization σ.

Enhancing Circular Dichroism Signals with Vector Beams.

Circular dichroism (CD) is broadly employed for distinguishing molecular chiralities. However, its practical application is often limited by the weak magnitude of chiral signal. We propose to use azimuthally and radially polarized vector beams to probe CD spectra. By taking advantage of the strong longitudinal components of the vector beams, the transmitted light can be detected in the radial direction. The resulting CD signal is several orders of magnitude stronger than conventional CD signal with plane waves. Quantitative analysis and numerical simulations show that the enhancement factor is independent of molecular properties and can be increased by decreasing the path length of the sample cuvette and the interaction cross section between the light beam and molecular sample. The proposed novel CD spectroscopy is feasible with the current optical technology.

Gigantic vortical differential scattering as a monochromatic probe for multiscale chiral structures

Spin angular momentum of light is vital to investigate enantiomers characterized by circular dichroism (CD), widely adopted in biology, chemistry, and material science. However, to discriminate chiral materials with multiscale features, CD spectroscopy normally requires wavelength-swept laser sources as well as wavelength-specific optical accessories. Here, we experimentally demonstrate an orbital-angular-momentum-assisted approach to yield chiroptical signals with monochromatic light. The gigantic vortical differential scattering (VDS) of ∼120% is achieved on intrinsically chiral microstructures fabricated by femtosecond laser. The VDS measurements can robustly generate chiroptical properties on microstructures with varying geometric features (e.g., diameters and helical pitches) and detect chiral molecules with high sensitivity. This VDS scheme lays a paradigm-shift pavement toward efficiently chiroptical discrimination of multiscale chiral structures with photonic orbital angular momentum. It simplifies and complements the conventional CD spectroscopy, opening possibilities for measuring weak optical chirality, especially on mesoscale chiral architectures and macromolecules.

Chiral discrimination by recollision enhanced femtosecond laser mass spectrometry

Chiral molecules and their interactions are critical in a variety of chemical and biological processes. Circular dichroism (CD) is the most widely used optical technique to study chirality, often performed in a solution phase. However, CD has low-efficiency on the order of 0.01–1%. Therefore, there is a growing need to develop high-efficiency chiroptical techniques, especially in gas-phase, to gain background-free in-depth insight into chiral interactions. By using mass spectrometry and strong-field ionization of limonene with elliptically polarized light, we demonstrate an efficient chiral discrimination method that produces a chiral signal of one to two orders of magnitude higher than the conventional CD. The chiral response exhibits a strong dependence on wavelength in the range of 1,300–2,400 nm, where the relative abundance of the ion yields alternates between the two enantiomers. The origin of enhanced enantio-sensitivity in intense laser fields is attributed to two mechanisms that rely on the recollision dynamics in a chiral system: (1) the excited ionic state dynamics mediated either by the laser field or by the recollision process, and (2) non-dipole effects that alter the electron’s trajectories. Our results can serve as a benchmark for testing and developing theoretical tools involving non-dipole effects in strong-field ionization of molecules.

Chirality detection of surface desorption products using photoelectron circular dichroism.

Chirality detection of gas-phase molecules at low concentrations is challenging as the molecular number density is usually too low to perform conventional circular dichroism absorption experiments. In recent years, new spectroscopic methods have been developed to detect chirality in the gas phase. In particular, the angular distribution of photoelectrons after multiphoton laser ionization of chiral molecules using circularly polarized light is highly sensitive to the enantiomeric form of the ionized molecule [multiphoton photoelectron circular dichroism (MP-PECD)]. In this paper, we employ the MP-PECD as an analytic tool for chirality detection of the bicyclic monoterpene fenchone desorbing from a Ag(111) crystal. We record velocity-resolved kinetics of fenchone desorption on Ag(111) using pulsed molecular beams with ion imaging techniques. In addition, we measure temperature-programmed desorption spectra of the same system. Both experiments indicate weak physisorption of fenchone on Ag(111). We combine both experimental techniques with enantiomer-specific detection by recording MP-PECD of desorbing molecules using photoelectron imaging spectroscopy. We can clearly assign the enantiomeric form of the desorption product fenchone in sub-monolayer concentration. The experiment demonstrates the combination of MP-PECD with surface science experiments, paving the way for enantiomer-specific detection of surface reaction products on heterogeneous catalysts for asymmetric synthesis.

Circular Dichroism Spectroscopy Identifies the β-Adrenoceptor Agonist Salbutamol As a Direct Inhibitor of Tau Filament Formation in Vitro.

Potential drug treatments for Alzheimer's disease (AD) may be found by identifying compounds that block the assembly of the microtubule-associated protein tau into neurofibrillar tangles associated with neuron destabilization and cell death. Here, a small library of structurally diverse compounds was screened in vitro for the ability to inhibit tau aggregation, using high-throughput synchrotron radiation circular dichroism as a novel tool to monitor the structural changes in the protein as it assembles into filaments. The catecholamine epinephrine was found to be the most effective tau aggregation inhibitor of all 88 screened compounds. Subsequently, we tested chemically similar phenolamine drugs from the β-adrenergic receptor agonist class, using conventional circular dichroism spectroscopy, thioflavin T fluorescence, and transmission electron microscopy. Two compounds, salbutamol and dobutamine, used widely in the treatment of respiratory and cardiovascular disease, impede the aggregation of tau in vitro. Dobutamine reduces both the rate and yield of tau filament formation over 24 h; however, it has little effect on the structural transition of tau into β-sheet structures over 24 h. Salbutamol also reduces the yield and rate of filament formation and additionally inhibits tau's structural change into β-sheet-rich aggregates. Salbutamol has a good safety profile and a half-life that facilitates permeation through the blood-brain barrier and could represent an expediated approach to developing AD therapeutics. These results provide the motivation for the in vivo evaluation of pre-existing β-adrenergic receptor agonists as a potential therapy for AD through the reduction of tau deposition.

Circular Phase-Dichroism of Chiral Metasurface Using Birefringent Interference.

Circular phase-dichroism (CPD) has been suggested for the characterization of chiral metasurfaces in supplementing the conventional circular dichroism (CD). Conventional CD probes the bulk properties while the CPD, reported recently in 2D chiral metasurfaces using an air-gap Fabry-Perot setup, is based on the surface properties. Here we propose and demonstrate a robust birefringent interference approach to obtain the CPD by replacing the air-gap with a uniaxial birefringent material in which interference is realized by the difference in the refractive indexes for the ordinary and extraordinary components of the material. We measure the transmission phases of metasurfaces fabricated on birefringent sapphire substrates and obtain clear CPDs for chiral metasurfaces but vanishing for achiral metasurfaces. Importantly, our approach can be applied to metasurfaces fabricated on nonbirefringent substrates by add-on birefringent materials. We confirm our results by a Jones matrix method using data obtained from full-wave simulations, and good agreements with experiments are obtained.

Measuring circular phase-dichroism of chiral metasurface

Abstract The ability of chiral media to differentiate circularly polarized light is conventionally characterized by circular dichroism (CD) which is based on the difference in the absorption of the incident light for different polarizations. Thus, CD probes the bulk properties of chiral media. Here, we introduce a new approach termed as circular phase-dichroism that is based on the surface properties and is defined as the difference of the reflection phase for different circularly polarized incident lights in characterizing chiral media. As a demonstration, we measure the reflection phase from planar chiral sawtooth metasurface for circularly polarized light in the visible range using a simple Fabry Perot interference technique. The measured circular phase-dichroism is also crosschecked by conventional CD measurement of the transmitted light and by full-wave simulations. Our results demonstrate the potential applications of circular phase-dichroism in sensing and metasurface characterizations.

Measurement of Circular Dichroism Spectra without Control of a Phase Modulator using Retardation Domain Analysis

This study investigated the measurement of circular dichroism (CD) spectra without controlling a phase modulator. In a conventional CD system, the peak retardation of the phase modulator must remain constant over the observed wavelength range. Thus, the phase modulator must be controlled to maintain an appropriate modulation degree at an observed wavelength. In contrast, CD obtained using retardation domain analysis is not affected by peak retardation. Consequently, CD spectra can be measured without control of the phase modulator, which was experimentally demonstrated in this study. Additionally, linear dichroism spectra were obtained using retardation domain analysis.

Circular-Dichroism and Synchrotron-Radiation Circular-Dichroism Spectroscopy as Tools to Monitor Protein Structure in a Lipid Environment.

Circular-dichroism (CD) spectroscopy is a powerful tool for the secondary-structure analysis of proteins. The structural information obtained by CD does not have atomic-level resolution (unlike X-ray crystallography and NMR spectroscopy), but it has the great advantage of being applicable to both nonnative and native proteins in a wide range of solution conditions containing lipids and detergents. The development of synchrotron-radiation CD (SRCD) instruments has greatly expanded the utility of this method by extending the spectra to the vacuum-ultraviolet region below 190nm and producing information that is unobtainable by conventional CD instruments. Combining SRCD data with bioinformatics provides new insight into the conformational changes of proteins in a membrane environment.