Chirality Inversion Research Articles

Synthesis of nature product kinsenoside analogues with anti-inflammatory activity

Kinsenoside is the major bioactive component from herbal medicine with a broad range of pharmacological functions. Goodyeroside A, an epimer of kinsenoside, remains less explored. In this report we chemically synthesized kinsenoside, goodyeroside A and their analogues with glycan variation, chirality inversion at chiral center(s), and bioisosteric replacement of lactone with lactam. Among these compounds, goodyeroside A and its mannosyl counterpart demonstrated superior anti-inflammatory efficacy. Furthermore, goodyeroside A was found to suppresses inflammatory through inhibiting NF-κB signal pathway, effectively. Structure-activity relationship is also explored for further development of more promising kinsenoside analogues as drug candidates.

Dense skyrmion crystal stabilized through interfacial exchange coupling: Role of in-plane anisotropy

A Monte Carlo simulated-annealing algorithm was used to study the magnetic state in an in-plane helimagnet layer on triangular lattice that exchange couples to an underlayer with strong out-of-plane anisotropy. In the single helimagnet layer with in-plane anisotropy (K), the formation of labyrinthlike domains with local spin spirals, instead of parallel stripes, is favored, and these domains rapidly transform into dense skyrmion crystals with increasing interfacial exchange coupling (J′), equivalent to a virtual magnetic field, and finally evolve to an out-of-plane uniform state at large enough J′. Moreover, with increasing K, the skyrmion crystal state can vary from regular 6-nearest-neighboring circular skyrmion arrangement to irregular squeezed skyrmions with less than 6 nearest neighbors when the in-plane anisotropy energy is higher than the interfacial exchange energy as the skyrmion number is maximized. Finally, we demonstrated that the antiferromagnetic underlayer cannot induce skyrmions while the chirality inversion can be achieved on top of an out-of-plane magnetization underlayer with 180° domain walls, supporting the experimental findings in FeGe thin film. This compelling advantage offers a fertile playground for exploring emergent phenomena that arise from interfacing magnetic skyrmions with additional functionalities.

Stereoselective Pharmacokinetics and Chiral Inversions of Some Chiral Hydroxy Group Drugs.

Chiral safety, especially chiral drug inversion in vivo, is the top priority of current scientific research. Medicine researchers and pharmacists often ignore that one enantiomer will be converted or partially converted to another enantiomer when it is ingested in vivo. So that, in the context that more than 50% of the listed drugs are chiral drugs, it is necessary and important to pay attention to the inversion of chiral drugs. The metabolic and stereoselective pharmacokinetic characteristics of seven chiral drugs with one chiral center in the hydroxy group were reviewed in vivo and in vitro including the possible chiral inversion of each drug enantiomer. These seven drugs include (S)-Mandelic acid, RS-8359, Tramadol, Venlafaxine, Carvedilol, Fluoxetine and Metoprolol. The differences in stereoselective pharmacokinetics could be found for all the seven chiral drugs, since R and S isomers often exhibit different PK and PD properties. However, not every drug has shown the properties of one direction or two direction chiral inversion. For chiral hydroxyl group drugs, the redox enzyme system may be one of the key factors for chiral inversion in vivo. In vitro and in vivo chiral inversion is a very complex problem and may occur during every process of ADME. Nowadays, research on chiral metabolism in the liver has the most attention, while neglecting the chiral transformation of other processes. Our review may provide the basis for the drug R&D and the safety of drugs in clinical therapy.

Multiple Twisted Chiral Nematic Structures in Cylindrical Confinement

In this article, we theoretically and numerically study the chirality and saddle-splay elastic constant ( K 24 ) -enabled stability of multiple twist-like nematic liquid crystal (LC) structures in cylindrical confinement. We focus on the so-called radially z-twisted (RZT) and radially twisted (RT) configurations, which simultaneously exhibit twists in different spatial directions. We express the free energies of the structures in terms of dimensionless wave vectors, which characterise the structures and play the roles of order parameters. The impact of different confinement anchoring conditions is explored. A simple Landau-type analysis provides an insight into how different model parameters influence the stability of structures. We determine conditions for which the structures are stable in chiral and also nonchiral LCs. In particular, we find that the RZT structure could exhibit macroscopic chirality inversion upon varying the relevant parameters. This phenomenon could be exploited for the measurement of K 24 .

Preparation of amylose-poly(methyl methacrylate) inclusion complex as a smart nanocarrier with switchable surface hydrophilicity

Amylose, as a linear biopolymer, tends to form helical inclusion complexes with suitable guest species. This is of great importance for a variety of applications, especially in the pharmaceutical and food industry. In this study, we propose an approach for the preparation of a novel inclusion complex with switchable surface hydrophilicity. For this purpose, amylose was first conjugated to ethylene diamine hydrophilic residues. Then, the short chains of the hydrophobic poly(methyl methacrylate, PMMA) were grafted onto the cavity of amylose through atom transfer radical polymerization (ATRP). According to CD spectroscopy results, the amylose-PMMA inclusion complexes displayed solvent-directed helical chirality inversion using either DMSO or water as a solvent. Fluorescence imaging, AFM and DLS techniques revealed the solvent-dependent surface hydrophilicity of the amylose-PMMA inclusion complex. Interestingly, its morphological studies displayed a central cavity, which makes it suitable for carrying cargoes in drug delivery applications. Obtaining the amylose-polymer inclusion complexes with tailorable hydrophilicity of both the exterior surface and the interior cavity can be of paramount importance for a wide variety of bio-applications.

Self-Assembly and Temperature-Driven Chirality Inversion of Cholesteryl-Based Block Copolymers

Block copolymers (BCPs), comprising a poly(methyl methacrylate) (PMMA) block and a poly(cholesteryloxyhexyl methacrylate) (PChMA) block, were synthesized via reversible addition–fragmentation chain transfer polymerization. The self-assembly of the liquid crystalline BCPs was characterized by differential scanning calorimetry, polarized optical microscopy, and synchrotron-based small/wide-angle X-ray scattering. The results indicate the formation of both tilted and nontilted chiral smectic (SmC* and SmA*) phases. A phase transition from the SmA* to SmC* phase on cooling was observed for BCPs but not for PChMA homopolymers. The layer spacing (5.00 ± 0.18 nm) between those can be controlled to maintain the number of ChMA units while varying the lengths of the PMMA block, thus introducing systematically the SmC* phase. Furthermore, BCPs with the short PMMA block showed inversion of chirality at specific temperatures; however, for PChMA attached with the long PMMA block, no chirality inversion was observed. This mode of chirality switching, investigated by circular dichroism, NMR, and theoretical studies, is associated with the methyl substituents in the backbone affecting the packing of the polymers. The basic rules, described here, have the potential to be implemented for the design of a wide range of functional materials, where helix–helix conversion is of use.

PH-Controlled Chirality Inversion in Enantiodifferentiating Photocyclodimerization of 2-Antharacenecarboxylic Acid Mediated by γ-Cyclodextrin Derivatives.

Several γ-cyclodextrin (γ-CDx) derivatives were used as chiral hosts for the photocyclodimerization of 2-anthracenecarboxylic acid (AC). The effect of pH on photoreactivity and stereochemical outcome of photoproducts was investigated. Upon changing the solution pH, the stereochemical outcome of HH cyclodimer 3 was inverted from 25.2% to -64.4% and 41.2% to -76.2%, respectively, in the photocyclodimerization of AC mediated by bis-quinoline-modified γ-CDx 7 and its N-methylated derivative 8.

Controlled chiral transcription and efficient separation via graphene oxide encapsulated helical supramolecular assembly

Chiral transcription and enantioselective separation have garnered significant research interests and showed potential for a broad range of practical applications. Here, we present a novel and facile strategy for chiral templating and enantiomers resolution by coating metal-ion-mediated l-phenylalanine derivatives (LPF/M) with graphene oxide (GO) via simply mixing. The LPF/M hydrogels precipitate from the liquid by encapsulation of GO through coordination interactions and hydrogen bonds, making heterogeneous transfer and separation possible. The chirality inversion of the internal LPF/M nanostructure could be triggered by different addition of metal ions, which further provides means for controlled chiral transfer of guest molecules on the outer GO surfaces as demonstrated in the transcription of thioflavin T (ThT) and 3-aminopyridine (AP) at the supramolecular level. Changing the metal ions also provides control over enantiomer selectivity with outstanding efficiency and reproducibility, as revealed by the separation of racemic mixtures of phenylanine (>98%), lysine (>96%), and histidine (>97%). In addition, the resultant hybrid materials exhibit excellent environmental stability and reusability (more than 20 times) with significant separation efficiency. More importantly, the GO-coated LPF/M could determine the enantiomeric composition of various chiral substrates. The proposed strategy opens up a promising avenue for practical chiral separation application.

Self-Assembly Evolution of N-Terminal Aromatic Amino Acids with Transient Supramolecular Chirality.

Deep understanding and fine tailoring of spontaneous structural evolution of self-assembled arrays are pivotal in the rational design of advanced soft materials. However, an indistinct structure-property relationship and pathway complexity in self-assembly lead to a considerable challenge. Herein, we reveal the self-assembly pathway complexity in spontaneous aggregation of several N-terminated aromatic amino acids. By primarily tuning the incubation time, building blocks appended with alanine and serine selectively form 1:1 hydrated clathrates, enabling the microfiber to transition to crystals. The dynamic water intercalation process was studied by incubation time-dependent morphological changes, powder X-ray diffraction, and single-crystal structure analysis. A pronounced amino acid residue effect on the self-assembly evolution was reflected by supramolecular chirality inversion of the building block having the phenylalanine residue, accomplishing dynamic M- to P-helicity transition within a confined time scale.

Solvent-Induced Sign Inversion of Circularly Polarized Luminescence: Control of Excimer Chirality by Hydrogen Bonding

A series of pyrenes sandwiched by axially chiral 1,1'-binaphthyls were synthesized. Among them, (R,R)-3 possessing 2-hydroxy-3,3'-dimethylbinaphthyls exhibited solvent-dependent inversion of the sign of circularly polarized luminescence (CPL) without a change in emission wavelength. The (-)- and (+)-CPL were detected in nonpolar and polar solvents, respectively, with glum values of -0.012 and +0.012. This switching property originates from the inversion of excimer chirality caused by the presence or absence of intermolecular hydrogen bonds in the excited state. The CPL intensity was also changed by variation of the temperature and concentration.

A family of diastereomeric dodecanuclear coordination cages based on inversion of chirality of individual triangular cyclic helicate faces.

The dodecanuclear coordination cage [Cd12(Lnaph)12(Lmes)4](BF4)24 consists of a set of four triangular, trinuclear helical panels {Cd3(μ-Lnaph)3}6+ (based on ditopic bridging ligands Lnaph), which are connected by four tritopic ligands Lmes. The result is that the four triangular helical panels and the four Lmes-capped triangular faces of the cuboctahedral core form two alternating subsets of the eight triangular faces of the cuboctahedron. Crystallographic investigations revealed that the triangular helicate faces can have ‘clockwise’ (C) or ‘anticlockwise’ (A) helicity, and that the helicity of each face can vary independently of the others as they are mechanically separated. This generates a set of three diastereoisomers in which all four cyclic helicate faces in the cuboctahedron have the same chirality (AAAA/CCCC enantiomers with T symmetry; AAAC/CCCA enantiomers with C3 symmetry; and achiral AACC with S4 symmetry). This mirrors the known behaviour of many simpler M4L6 tetrahedral cages which can likewise exist as T, C3 or S4 isomers according to the sense of tris-chelate chirality around each individual metal centre: but here it is translated onto a much larger scale by the four chiral units being entire trinuclear helicate faces rather than single metal centres. 1H NMR spectroscopy confirms the presence of the three diastereoisomers with their different molecular symmetries in a ratio slightly different from what is expected on purely statistical grounds; and 1H NMR measurements on a non-equilibrium sample (enriched by manual crystal-picking before preparing the solution) showed that the distribution does not change over several weeks in solution, indicating the kinetic inertness of the cage assemblies.

Molecule to Supramolecule: Chirality Induction, Inversion, and Amplification in a Mg(II)porphyrin Dimer Templated by Chiral Diols.

A clear and unambiguous rationalization of chirality induction, amplification, and subsequent inversion processes has been demonstrated using an achiral Mg(II)porphyrin dimer (host) and a series of chiral diols (guests) upon stepwise formation of a 1:1 host-guest polymer and 1:2 host-guest monomer via intermolecular assembling and disassembling processes. Crystallographic characterizations are reported here for both the polymer and the monomeric complexes, which enable us to completely scrutinize the structural and geometrical changes systematically in rationalizing their optical properties. The sign of the CD couplets for both the polymer and monomer are just opposite between R and S guests, which suggests that the chirality is dictated solely by the stereogenic projection of the chiral centers. Stronger intra- and intermolecular coupling in the polymeric complexes is responsible for the highly enhanced CD couplets as compared to the monomer and have only intramolecular coupling as also observed in their X-ray structures. DFT studies clearly support the experimental observations.

Axial chirality inversion at a spiro carbon leads to efficient synthesis of polyimine macrocycle

The synthesis and conformational preferences of a novel chiral macrocyclic polyimine possessing spiro carbon atoms is described. The key feature of the synthesis is the incorporation of an axially chiral surrounding of quaternary carbon atom having four constitutionally identical substituents into the structure of the macrocycle. This is possible by partial hydrolysis, which enables the inversion of absolute configuration, of the spiro-acetal moiety. This approach allows to obtain the macrocyclic product with almost quantitative yield. The synthesis of rhombimine with enantiopure trans -1,2-diaminocyclohexane and racemic bisaldehyde with spiro carbon atoms yields single macrocyclic product with almost quantitative yield. This is possible by partial reverse hydrolysis and thus ring opening and the inversion of absolute configuration of the a conformationally stable spiro-acetal moiety. • Diastereoselective synthesis of spiro rhombimines. • Absolute configuration of spiro moiety changes during the reaction. • New mechanism for adapting the racemic substrate in the macrocyclization reaction.

Chiral Restructuring of Peptide Enantiomers on Gold Nanomaterials.

The use of biomolecules has been invaluable at generating and controlling optical chirality in nanomaterials; however, the structure and properties of the chiral biotemplate are not well understood due to the complexity of peptide-nanoparticle interactions. In this study, we show that the complex interactions between d-peptides and gold nanomaterials led to a chiral restructuring of peptides as demonstrated by circular dichroism and proteolytic cleavage of d-peptides via gold-mediated inversion of peptide chirality. The gold nanoparticles synthesized using d-peptide produce a highly ordered atomic surface and restructured peptide bonds for enzyme cleavage. Differences in gold nanoparticle catalyzed reduction of 4-nitrophenol were observed on the basis of the chiral peptide used in nanoparticle synthesis. Notably, the proteolytic cleavage of d-peptides on gold provides an opportunity for designing nanoparticle based therapeutics to treat peptide venoms, access new chemistries, or modulate the catalytic activity of nanomaterials.

Precise Manipulation of Temperature-Driven Chirality Switching of Molecular Universal Joints through Solvent Mixing.

Three chiral bicyclic pillar[5]arene derivatives termed as molecular universal joints (MUJs), were synthesized and separated enantiomerically. These MUJs showed temperature-driven chirality switching in certain solvents. Herein, it is demonstrated that temperature-driven chirality switching could also be realized by mixing two miscible organic solvents, in each of which chirality inversion is not accomplishable. Additionally, solvent mixing drastically varied the inversion temperature of the MUJs, for example, from far below zero to room temperature. Moreover, the temperature-driven Sp /Rp to Rp /Sp chirality switching direction could be reversed by the solvent mixing and it was critically controlled by the mixing ratios of the two solvents. These observations allowed precise manipulation of the chirality switching behavior of the MUJs. Such a chirality switching was ascribed to the influences of solvent and temperature on the in-out equilibrium of the side rings, which is delicately controlled by several processes, including the solvation/desolvation and the inclusion/exclusion of the side rings and solvent molecules. Crucially, the solvent mixing introduced new supramolecular processes, in particular the desolvation of solvent molecules from the mixed solvent system and the solvation of the side ring by the mixed solvent, which significantly disturbed the original in-out equilibrium of MUJs and drastically switched the entropy and enthalpy changes of conformational interconversion.

Inverting the Handedness of Circularly Polarized Luminescence from Light-Emitting Polymers Using Film Thickness.

The emission of circularly polarized light is central to many applications, including data storage, optical quantum computation, biosensing, environmental monitoring, and display technologies. An emerging method to induce (chiral) circularly polarized (CP) electroluminescence from the active layer of polymer light-emitting diodes (polymer OLEDs; PLEDs) involves blending achiral polymers with chiral small-molecule additives, where the handedness/sign of the CP light is controlled by the absolute stereochemistry of the small molecule. Through the in-depth study of such a system we report an interesting chiroptical property: the ability to tune the sign of CP light as a function of active layer thickness for a fixed enantiomer of the chiral additive. We demonstrate that it is possible to achieve both efficient (4.0 cd/A) and bright (8000 cd/m2) CP-PLEDs, with high dissymmetry of emission of both left-handed (LH) and right-handed (RH) light, depending on thickness (thin films, 110 nm: gEL = 0.51, thick films, 160 nm: gEL = -1.05, with the terms "thick" and "thin" representing the upper and lower limits of the thickness regime studied), for the same additive enantiomer. We propose that this arises due to an interplay between localized CP emission originating from molecular chirality and CP light amplification or inversion through a chiral medium. We link morphological, spectroscopic, and electronic characterization in thin films and devices with theoretical studies in an effort to determine the factors that underpin these observations. Through the control of active layer thickness and device architecture, this study provides insights into the mechanisms that result in CP luminescence and high performance from CP-PLEDs, as well as demonstrating new opportunities in CP photonic device design.

Chirality invertible superstructure mediated active planar optics

Active planar optical devices that can dynamically manipulate light are highly sought after in modern optics and nanophotonics. The geometric phase derived from the photonic spin-orbit interaction provides an integrated strategy. Corresponding elements usually suffer from static functions. Here, we introduce an inhomogeneously self-organized anisotropic medium featured by photo-invertible chiral superstructure to realize geometric phase elements with continuously tunable working spectrum and light-flipped phase profile. Via preprograming the alignment of a cholesteric liquid crystal mixed with a photo-responsive chiral dopant, we demonstrate light-activated deflector, lens, Airy beam and optical vortex generators. Their polychromatic working bands are reversibly tuned in an ultra-broadband over 1000 nm covering green to telecomm region. The chirality inversion triggers facile switching of functionalities, such as beam steering, focusing/defocusing and spin-to-orbital angular momentum conversion. This work offers a platform for advanced adaptive and multifunctional flat optics with merits of high compactness, low loss and broad bandwidth.

Light-driven molecular switch for reconfigurable spin filters

Artificial molecular switches and machines that enable the directional movements of molecular components by external stimuli have undergone rapid advances over the past several decades. Particularly, overcrowded alkene-based artificial molecular motors are highly attractive from the viewpoint of chirality switching during rotational steps. However, the integration of these molecular switches into solid-state devices is still challenging. Herein, we present an example of a solid-state spin-filtering device that can switch the spin polarization direction by light irradiation or thermal treatment. This device utilizes the chirality inversion of molecular motors as a light-driven reconfigurable spin filter owing to the chiral-induced spin selectivity effect. Through this device, we found that the flexibility at the molecular scale is essential for the electrodes in solid-state devices using molecular machines. The present results are beneficial to the development of solid-state functionalities emerging from nanosized motions of molecular switches.

Molecular recognition of melamine and cyanuric acid by C2-symmetric phenylalanine based supramolecular hydrogels

Molecular recognition of achiral structural analogues, a remaining challenge for materials scientists and chemists, is the key to manipulating the applications and properties of supramolecular chiral materials. Herein, we report the molecular recognition of two harmful structural analogues i.e. melamine (MA) and cyanuric acid (CA) by using C2-symmetric phenylalanine chiral hydrogelators. Two distinct molecular recognition events between hydrogelator fibrils and triazine based achiral molecules are demonstrated: phenylalanine-co-melamine (PF-co-MA) gels showed chirality amplification while chirality inversion was observed for phenylalanine-co-cyanuric acid (PF-co-CA) gels. Moreover, viscoelastic properties and twist pitch were also regulated under the influence of the achiral molecules. Such phenomenon is mainly mediated by H-bonding among the two components, which may subtly change the arrangement of the molecules, in turn, the self-assembled nanostructures. This method of using C2-symmetric phenylalanine based gelators in the recognition of the achiral molecules may be broadly applicable for a wide variety of molecular recognition partners such as sugars.

Light‐Activated Liquid Crystalline Hierarchical Architecture Toward Photonics

AbstractHierarchical architectures are of vital importance in materials science and nanotechnology. Among various building blocks, liquid crystals (LCs) have attracted particular attention due to their excellent controllability of self‐assembly behavior and the resultant physical properties. In recent years, interest in light‐activated LC hierarchical superstructures has emerged for a wide range of applications beyond LC displays. This report consists of two main parts: the light‐activated LC hierarchical architectures and their corresponding photonic applications. In the first part, different smectic layer curvature controlling methods are introduced to produce periodic defect arrays. By taking the advantages of photoalignment techniques and light‐driven molecular motors, cholesteric LC helical superstructures are highly manipulated, including pitch tuning, helix rotation, and chirality inversion. As a mutually concerned scientific issue, the photoresponsive properties of blue phase (BP) hierarchical superstructures are also introduced, enabling unique BP materials and devices driven by a facile light stimulation. Moreover, traditional optics (microlens and beam steering) and advanced photonics (specific optical field generation and LC lasers) are reviewed in the second part. It is believed that the developments introduced here can open a door for the concept of “smart optical materials” based on the self‐assembled soft LC superstructures.