Chiral Solutions Research Articles

Preparation of Chiral Stationary Phase Based on 1,1'-bi-2-Naphthol for Chiral Enantiomer Separation.

Two enantiomeric novel chiral stationary phases (CSPs) R-3-Amide-BINOL CSP (CSP-1) and S-3-Amide-BINOL CSP (CSP-2) were prepared using (R/S)-1,1'-bi-2-naphthol (BINOL) derivatives as chiral selectors. The structure of CSPs was characterized by nuclear magnetic resonance, scanning electron microscope and elemental analysis. Four chiral solutes were selected under normal phase HPLC conditions to evaluate the chiral separation ability of the two novel CSPs. The effects of mobile phase and acidic additives on enantiomeric separation were investigated. The combination of molecular docking simulation and experimental data has elucidated the crucial role of hydrogen bonds and π-π interactions formed between the analyte and CSP in chiral recognition, and different configurations of CSP can cause enantiomeric elution sequence reversal, indicating that the configuration of chiral selectors in CSP has a significant impact on chiral recognition ability.

Exploring the Effects of Optically Active Solvents in Chiral Chromatography on Polysaccharide-Based Columns.

Exploring the effectiveness of optically active solvents as mobile-phase modifiers in chiral liquid chromatography (LC) can offer an additional new tool to tune the chiral selectivity. Hence, the potential of l-ethyl lactate (LEL), a biobased solvent of this nature, was explored for its distinctive interactions with both the mobile phase and analytes, as anticipated from its chiral nature. The findings reveal that LEL provides distinct selectivity compared to commonly used modifiers in chiral LC. Reversed-phase LC (RPLC)-type chiral separations were therefore compared under various conditions whereby LEL was partially or completely replacing common achiral solvents such as acetonitrile (ACN) and methanol (MeOH). An increase in chiral resolution was obtained in 8 of 16 test compounds. For 5 of them a decrease was obtained, and 3 test solutes did not offer satisfactory results under any of the tested conditions on the polysaccharide columns. When LEL was combined with methanol instead of ACN, worse results were obtained, presumably due to its protic nature. Moreover, LEL demonstrates excellent compatibility with salt additives and is fully miscible with aqueous phases. Interestingly, a steeper increase in chiral resolution is observed for LEL, as compared to ACN at lower temperatures. While LEL is somewhat hindered by its higher UV absorbance, it paves the way toward more simplified chiral screening platforms, whereby chiral solutions can be found for fewer columns and greener solvents such as LEL are incorporated. Finally, to elucidate the impact of chiral interactions between the solvent and analytes, the influence of d-ethyl lactate (DEL) was compared with that of LEL. The results revealed different interactions between the stereoisomers of ethyl lactate (EL) and chiral analytes, demonstrating an influence of optically active solvents on enantioseparations.

Optical directional differential operation enabled visual chirality detection.

Directional differential operation can extract the changes of directional information from complex signals, and plays an important role in target recognition and texture image processing. Here, we propose an optical directional differential operation based on large cross-polarization rotation, and realize the visual detection of chiral enantiomers. By using cross-polarization rotation in a specified direction, we design a corresponding directional spatial spectral transfer function whose transmission efficiency increases as the incident angle approaches the Brewster angle. The differential direction can be adjusted by changing the initial polarization state, and can be used to detect the concentration of chiral solutions. Finally, we apply the directional differential operation to achieve the visual detection of chiral enantiomers.

Heat of Dilution and Racemization of Chiral Amino Acid Solutions

Chiral interactions play a crucial role in both chemistry and biology. Understanding the behavior of chiral molecules and their interactions with other molecules is essential, and chiral interactions in solutions are particularly important for studying chiral compounds. Chirality influences the physical and chemical properties of molecules, including solubility, reactivity, and biological activity. In this work, we used isothermal titration calorimetry (ITC), a powerful technique for studying molecular interactions, including chiral interactions in solutions. We conducted a series of ITC measurements to investigate the heat of dilution and the heat of racemization of several amino acids (Asparagine, Histidine, Serine, Alanine, Methionine, and Phenylalanine). We also performed ITC measurements under different solute concentrations and temperatures to examine the effects of these parameters on chiral interactions, as well as the heat of dilution and racemization. The results of our measurements indicated that the heat of dilution, specifically the interactions between the solvent (water) and solute (chiral molecules), had a significant impact compared to the chiral interactions in the solution, which were found to be negligible. This suggests that the interactions between chiral molecules and the solvent play a more dominant role in determining the overall behavior and properties of the system. By studying chiral interactions in solutions, we can gain valuable insights into the behavior of chiral compounds, which can have implications in various fields, including drug design, chemical synthesis, and biological processes.

Stability analysis and soliton solutions of the (1+1)-dimensional nonlinear chiral Schrödinger equation in nuclear physics

The nonlinear Schrödinger equation equation is one of the most important physical models used in optical fiber theory to explain the transmission of an optical soliton. The field of chiral soliton propagation in nuclear physics is very interesting because of its numerous applications in communications and ultra-fast signal routing systems. The (1+1)-dimensional chiral dynamical structure that describes the soliton behaviour in data transmission is dealt with in this work using a variety of in-depth analytical techniques. This work has applications in particle physics, ionised science, nuclear physics, optics, and other applied mathematical sciences. We are able to develop a variety of solutions to demonstrate the behaviour of solitary wave structures, periodic soliton solutions, chiral soliton solutions, and bell-shaped soliton solutions with the use of applied techniques. Moreover, in order to verify the scientific calculations, the stability analysis for the observed solutions of the governing model is taken into consideration. In addition, the 3-dimensional, contour, and 2-dimensional visuals are supplied for a better understanding of the behaviour of the solutions. The employed strategies are dependable, uncomplicated, and effective; yet have not been utilised with the governing model in the literature that is now accessible. The resulting outcomes have impressive applications across a large number of study areas and computational physics phenomena representing real-world scenarios. The methods applied in this model are not utilized on the given models in previous literature so we can say that these describe the novelty of the work.

Plasmon-enhanced chiral absorption through electric dipole–electric quadrupole interaction

Enantioselective interactions of chiral molecules include distinct absorptions to opposite-handed circularly polarized light, known as chiral absorption. Traditionally, chiral absorption has been primarily attributed to electric dipole (ED) and magnetic dipole (MD) interaction with molecular chirality. However, this approach falls short for large molecules that support high-order multipolar components, such as electric quadrupole (EQ) moment. Here, we introduce a theoretical model to study the chiral absorption of large molecules in the presence of plasmonic nanostructures. This model considers both ED–MD interaction and ED–EQ interaction enhanced by a resonant structure. We numerically study such interactions of the chiral molecular solution in the vicinity of an achiral plasmonic nano-resonator. Our results show the distinct spectral information of the chiral medium on- and off-resonance of the resonator.

Optical Rotation Predictions for Rigid Chiral Solute-Achiral Solvent 1:1 Complexes with the PCM Model

We computed specific optical rotations (ORs) in solution for forty-two solute–solvent combinations, involving seventeen chiral solutes and eight achiral solvents, using cam-B3LYP/aug-cc-PVTZ. Explicit solvent effects were considered by calculating Boltzmann-averaged ORs from multiple conformers of a 1:1 solute–solvent complex, with additional implicit solvation. The PCM solvation model correctly predicted OR signs for all combinations, while the “1:1 complex plus PCM“ schemes misjudged it in two cases. Norbornenone in cyclohexane displayed the largest absolute deviation, indicating an inadequate description of the cam-B3LYP functional’s delocalized electronic structure. Incorrect OR signs for fenchone in methanol with the ”1:1 complex plus PCM“ schemes underscored the limitations of our simplistic scheme, which incorporates explicit effects by averaging one-to-one interactions between solute and solvent. Considering computational costs, the ”1:1 complex plus PCM“ scheme may not be the optimal choice for our test set, as the PCM model alone suffices for accurate specific OR calculations in solution.

The synergistic effect of typical chiral organic acids and solution chemistry conditions on the transport of 2-arylpropionic acid chiral derivatives in porous media

The hazards of man-made chiral compounds are of great public concern, with reports of worrying stereoselective compounds and an urgent need to assess their transport. This study evaluated the transport of 2-arylpropionic acid derivatives enantiomers (2-APA) in porous media under a variety of solution chemistry conditions via column packing assays. The results revealed the introduction of Malic acid (MA) enantiomers enhanced the mobility of 2-APA enantiomers, but the enhancement effect was different for different 2-APA enantiomers. Batch sorption experiments confirmed that the MA enantiomers occupied the sorption site of the quartz sand, thus reducing the deposition of the 2-APA enantiomer. Homo- or heterochirality between 2-APA and MA dominates the transport of 2-APA enantiomers, with homochirality between them triggering stronger retention and vice versa. Further evaluating the effect of solution chemistry conditions on the transport of 2-APA enantiomers, increased ionic strength attenuated the mobility of 2-APA enantiomers, whereas introduced coexisting cations enhanced the retention of 2-APA enantiomers in the column. The redundancy analyses corroborated these solution chemistry conditions were negatively correlated with the transport of 2-APA enantiomers. The coupling of pH and these conditions reveals electrostatic forces dominate the transport behavior and stereoselective interactions of 2-APA enantiomers. Distinguishing the transport of enantiomeric pair helps to understand the difference in stereoselectivity of enantiomers and promises to remove the more hazardous one.

High-sensitivity determination of ethanol concentration based on weak measurement system with Faraday effect

A high-sensitivity detection method is proposed for ethanol concentration based on weak measurement system with Faraday effect, and the improvement law of the sensitivity is studied. Different from chiral solution determination, the post-selection angle of the system is modified by the Faraday rotation angle of ethanol solution. The amplified photonic spin Hall effect acts as a probe for detecting the ethanol concentration in the system, and the sensitivity of ethanol concentration increases linearly with the increasing magnetic field intensity. Then we use the method to determine the ethanol concentration of commercial liquor, whose determination values are consistent with the label values and Raman spectroscopy results. Compared to other methods such as Raman spectrometry, the method has the advantages of real time, non-invasiveness, low cost and high sensitivity. Finally, the sensitivity of ethanol concentration can be further improved by designing of a suitable BK7-medium structure, and the sensitivity of 9.72 /vol% is achievable for the range 0 vol% ∼100 vol% of ethanol solutions.

Spatially Resolved Anisotropic Natural Abundance Deuterium 2D-NMR Spectroscopy Using Bimesophasic Lyotropic Chiral Systems.

In this paper, we describe, for the first time, the combined and original use of spatially resolved anisotropic natural abundance deuterium (ANAD) 2D-NMR experiments and bimesophasic lyotropic chiral systems to extract two independent sets of anisotropic parameters such as 2H-RQCs from a single NMR sample. As a pioneering example, we focus on a mixture of immiscible polypeptides (PBLG) and polyacetylene helical polymers (L-MSP) dissolved in weakly polar organic solvents (chloroform). Nondeuterated (D)-(+)-camphor is used as a model chiral solute. By providing two series of 2H-RQCs, this new analytical approach paves the way for applications in 3D structure elucidation with increased reliability and also opens up original investigations in terms of spectral enantiomeric discriminations and mixing of helical polymers.

Oxidation Analysis of l-Cysteine with a Chiral Sensor Based on Quantum Weak Measurement.

l-Cysteine, distinguished by its possession of reactive sulfhydryl groups within its molecular structure, plays a significant role in both biological systems and the pharmaceutical industry. It stands not only as a natural component integral to the constitution of glutathione but also as the principal precursor for the synthesis of l-cystine through an oxidation reaction. This study endeavors to introduce a novel approach to l-cysteine analysis, capitalizing on its optical activity, whereby an optical rotation detection system grounded in the principles of quantum weak measurement is proffered. The optical rotation angle corresponding to the concentration of chiral solutions can be accurately ascertained through spectral analysis. In practical implementation, a chiral sensing system, boasting a sensitivity of 372 nm/rad, was meticulously constructed, leveraging the concept of weak value amplification. Then, the real-time monitoring of chemical reactions involving l-cysteine and dimethyl sulfoxide was performed. Under the specific experimental conditions outlined in this investigation, it was observed that the oxidation process culminated within approximately 12 h. The application of weak measurement-based chiral sensors holds immense potential, providing robust technical support for real-time monitoring in fields such as chiral analysis and the synthesis of chiral pharmaceutical compounds.

Pairing effect on critical spin in chiral rotation

The critical spin Ic (or critical frequency ħωc) represents the minimum spin (or rotational frequency) required for stable chiral solutions in nuclear systems. The effect of pairing on the critical spin has been examined for the particle-hole configuration π(1h11/2)⊗ν(1h11/2)−1 with a triaxial deformation parameter of γ=30∘ using the particle rotor model, which treats the total angular momentum as a good quantum number. Increasing pairing interaction keeps the critical spin Ic constant, but decreases the critical rotational frequency ħωc. This is due to that the enhanced pairing interaction causes valence nucleons angular momenta to align preferentially along the medium axis, resulting in a larger effective collective moment of inertia and facilitating the emergence of chiral rotation at a lower frequency. However, even with an increase in pairing gap from 0.0 to 2.0MeV, the resulting increase in medium axis alignment is less than 1ħ, which is insufficient to change the value of the critical spin Ic. This study suggests that the critical spin remains robust against the influence of pairing interaction.

Plasmon-enhanced circular dichroism spectroscopy of chiral drug solutions.

We investigate the potential of surface plasmon polaritons at noble metal interfaces for surface-enhanced chiroptical sensing of dilute chiral drug solutions with nl volume. The high quality factor of surface plasmon resonances in both Otto and Kretschmann configurations enables the enhancement of circular dichroism differenatial absorption thanks to the large near-field intensity of such plasmonic excitations. Furthermore, the subwavelength confinement of surface plasmon polaritons is key to attain chiroptical sensitivity to small amounts of drug volumes placed around ≃100 nm by the metal surface. Our calculations focus on reparixin, a pharmaceutical molecule currently used in clinical studies for patients with community-acquired pneumonia, including COVID-19 and acute respiratory distress syndrome. Considering realistic dilute solutions of reparixin dissolved in water with concentration ≤5 mg/ml and nl volume, we find a circular-dichroism differential absorption enhancement factor of the order ≃20 and chirality-induced polarization distortion upon surface plasmon polariton excitation. Our results are relevant for the development of innovative chiroptical sensors capable of measuring the enantiomeric imbalance of chiral drug solutions with nl volume.

Selective Chirality Transfer to the Bis(trifluoromethylsulfonyl)imide Anion of an Ionic Liquid.

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.

Influence of Solvent Properties on the Measurement Accuracy of Specific Rotation of Chiral Molecular Solutions Based on Photonic Spin Hall Effect

Chirality distinguishing of biomolecules has attracted much attention in numerous fields. When detecting the chirality of molecules based on the optical rotation characteristics, the detection accuracy of specific rotation is closely related to solvent properties. Herein, taking amino acids as an example, in the case of changing the type, potential of hydrogen value, and concentration of solvents, respectively, the specific rotation is measured using spin Hall effect of light based on weak measurement. The results indicate that the specific rotation values of chiral molecules are different in different types of solvents. When phosphate buffered saline is used as the solvent, the detection sensitivity of chiral molecules is higher under alkaline conditions. When the pH value is fixed, the detection performance under the solvent concentration of 0.1 m is better than that of 0.01 or 0.001 m. The study shows that the solvent properties affect the specific rotation detection of chiral molecular solutions. Proper solvent properties can improve its accuracy, which is of great significance to promote the sensitivity of chiral discrimination.

Anisotropic 1 H STD-NMR Spectroscopy: Exploration of Enantiomer-Polypeptide Interactions in Chiral Oriented Environments.

The front cover artwork is provided by Dr. Philippe Lesot's group (NMR in Oriented Media, ICMMO, UMR CNRS 8182) at Université Paris-Saclay, France. The image shows four pieces of a puzzle: the magnet of an NMR spectrometer, the principle of the 1 H STD-NMR experiment and the 3D helical structure of the poly-γ-benzyl-L-glutamate polymer leading to a chiral liquid-crystalline phase that discriminates the enantiomers of a model chiral solute (1-phenethyl alcohol). Putting these pieces of the puzzle together allows us to identify the hydrogen sites of each enantiomer interacting with the polypeptide side chain. These new outcomes are a further step towards a global understanding of the chiral recognition that occurs in such media. Read the full text of the Research Article at 10.1002/cphc.202200508.

Cover Feature: Chirality Transfer from an Innately Chiral Nanocrystal Core to a Nematic Liquid Crystal 2: Lyotropic Chromonic Liquid Crystals (ChemPhysChem 3/2023)

The Cover Feature illustrates the formation of homochiral nematic lyotropic chromonic liquid crystal tactoids formed by disodium cromoglycate in water by the addition of cromoglycate surface-modified cellulose nanocrystals (CNCs) as chiral solutes. Using CNCs with an inherently chiral core reveals that biorenewable chiral solutes can serve as suitably powerful and increasingly multipurpose chiral additives. More information can be found in the Research Article by Diana P. N. Gonçalves, Timothy Ogolla, and Torsten Hegmann.

Enantioselectivity of chiral dihydromyricetin in multicomponent solid solutions regulated by subtle structural mutation.

Multicomponent crystals of a chiral drug with non-chiral components have attracted increasing attention in the application of enantiomer purification and regulation of the physicochemical properties of crystalline materials. Crystalline solid solutions provide opportunities for fine-tuning material properties because of continuously adjustable component stoichiometry ratios. The synthesis, crystal structure, thermodynamics and solid-state enantioselectivity of a series of multicomponent crystals of chiral dihydromyricetin (DMY) with caffeine (CAF) or theophylline (THE) were investigated and the results reveal how the subtle change of molecular structure of the coformer dictates the enantiomer selectivity in multicomponent cocrystals. A series of multicomponent cocrystal solvates of chiral DMY with CAF and THE were synthesized by the slurry cocrystallization method in acetonitrile. Although most racemic mixtures crystallize as racemic compounds or conglomerates, both DMY-CAF and DMY-THE crystallize as chiral solid solutions, unveiled by pseudo-binary melt phase diagrams and pseudo-ternary solution phase diagrams. Crystal structures of Rac-DMY-CAF, R,R-DMY-CAF, Rac-DMY-THE and R,R-DMY-THE are reported for the first time via single-crystal X-ray diffraction, displaying two distinct types of solid solution differing in mixing scale of enantiomers spanning several orders of magnitude. Surprisingly, this remarkable impact on enantiomer discrimination was simply achieved by the reduction of a methyl group of CAF to the THE coformer, which was further rationalized from their crystal structures and intermolecular interactions. Collectively, this work has demonstrated that a subtle change in the molecular structure of a coformer can regulate enantioselectivity in crystalline materials, guiding the purification of chiral racemic compounds via the cocrystallization method and the design of solid-solution crystalline materials.

Poly(carboxyethyl acrylate-co-ethylene glycol dimethacrylate) precursor monolith with bonded (S)-(-)-1-(2-naphthyl) ethylamine ligands for use in chiral and achiral separations by capillary electrochromatography

In this research report, the previously developed poly(carboxyethyl acrylate-co-ethylene glycol dimethacrylate) precursor monolith (referred to as carboxy monolith) is further exploited in the preparation of a chiral stationary phase for enantiomeric separations. The carboxy monolith precursor was subjected to post polymerization functionalization (PPF) with the chiral selector (S)-(-)-1-(2-naphthyl) ethylamine (NAS) at room temperature in the presence of N, N´-dicyclohexylcarbodiimide (DCC) in chloroform. The DCC, which is an organic soluble carbodiimide, permits the linkage for the amine functionality of the chiral ligand NAS to the carboxy group of the monolithic surface forming a stable amide linkage. The NAS column thus obtained allowed not only enantiomeric separations in the RP mode via its chiral site but also the separation of nonpolar species via its achiral functionality offering both hydrophobic and π-π interactions for aromatic compounds such toluene derivatives and polyaromatic hydrocarbons. The dual interaction sites (e.g., chiral, and achiral) of the NAS present a convenient column for the separations of slightly polar and nonpolar chiral and achiral solutes in the RP mode.

Estimating the concentration of chiral media with bright squeezed light

The concentration of a chiral solution is a key parameter in many scientific fields and industrial processes. This parameter can be estimated to high precision by exploiting circular birefringence or circular dichroism present in optically active media. Using the quantum Fisher information formalism, we quantify the performance of Gaussian probes in estimating the concentration of chiral analytes. We find that bright-polarization squeezed state probes provide a quantum advantage over equally bright classical strategies that scales exponentially with the squeezing factor for a circularly birefringent sample. Four-fold precision enhancement is achievable using state-of-the-art squeezing levels and intensity measurements.