Chirality Transfer Research Articles

Hierarchical chirality transfer of perylene diimide-tethered pillar[5]arenes for configuration and type differentiation of amino acid derivatives

Perylene diimide-tethered pillar[5]arene derivatives showed significantly varied circular dichroism (CD) spectral responses towards different amino acid derivatives in both the dispersed and aggregated forms.

Enantioselective organocatalytic strategies to access noncanonical α-amino acids.

Organocatalytic asymmetric synthesis has evolved over the years and continues to attract the interest of many researchers worldwide. Enantiopure noncanonical amino acids (ncAAs) are valuable building blocks in organic synthesis, medicinal chemistry, and chemical biology. They are employed in the elaboration of peptides and proteins with enhanced activities and/or improved properties compared to their natural counterparts, as chiral catalysts, in chiral ligand design, and as chiral building blocks for asymmetric syntheses of complex molecules, including natural products. The linkage of ncAA synthesis and enantioselective organocatalysis, the subject of this perspective, tries to imitate the natural biosynthetic process. Herein, we present contemporary and earlier developments in the field of organocatalytic activation of simple feedstock materials, providing potential ncAAs with diverse side chains, unique three-dimensional structures, and a high degree of functionality. These asymmetric organocatalytic strategies, useful for forging a wide range of C-C, C-H, and C-N bonds and/or combinations thereof, vary from classical name reactions, such as Ugi, Strecker, and Mannich reactions, to the most advanced concepts such as deracemisation, transamination, and carbene N-H insertion. Concurrently, we present some interesting mechanistic studies/models, providing information on the chirality transfer process. Finally, this perspective highlights, through the diversity of the amino acids (AAs) not selected by nature for protein incorporation, the most generic modes of activation, induction, and reactivity commonly used, such as chiral enamine, hydrogen bonding, Brønsted acids/bases, and phase-transfer organocatalysis, reflecting their increasingly important role in organic and applied chemistry.

Achiral substituent- and stoichiometry-controlled inversion of supramolecular chirality and circularly polarized luminescence in ternary co-assemblies.

Handedness inversion of supramolecular chirality and circularly polarized luminescence (CPL) in assembled systems containing more than two components with higher complexity is of prominent importance to simulate biological multicomponent species and design advanced chiral materials, but it remains a considerable challenge. Herein, we have successfully developed ternary co-assembly systems based on aromatic amino acids, vinylnaphthalene derivatives and 1,2,4,5-tetracyanobenzene with effective chirality transfer. Notably, the handedness of supramolecular chirality and CPL can be readily inverted by changing the residues of amino acids, the substituents of achiral vinylnaphthalene derivatives, or by adjusting the stoichiometric ratio. The hydrogen bonds, charge transfer interactions, and steric hindrance are proved to be the crucial factors for the chirality inversion. This flexible control over chirality not only offers insights into developing multicomponent chiral materials with desirable handedness from simple molecular building blocks, but also is of practical value for use in chiroptics, chiral sensing, and photoelectric devices.

Self-Assembled Metal-Coordination Nanohelices as Efficient and Robust Chiral Supramolecular Catalysts for Enantioselective Reactions.

The development of chiral nanostructures-based supramolecular catalysts with satisfied enantioselectivity remains a significantly more challenging task. Herein, the synthesis and self-assembly of various amino acid amphiphiles as chiral supramolecular catalysts after metal ion coordination is reported and systematically investigate their enantioselectivity in asymmetric Diels-Alder reactions. In particular, the self-assembly of l/d-phenylglycine-based amphiphiles (l/d-PhgC16 ) and Cu(II) into chiral supramolecular catalysts in the methanol/water solution mixture is described, which features the interesting M/P nanohelices (diameter ≈8nm) and mostly well-aligned M/P nanoribbons (NRs). The M/P supramolecular catalysts show both high but inverse enantioselectivity (>90% ee) in Diels-Alder reactions, while their monomeric counterparts display nearly racemic products. Analysis of the catalytic results suggests the outstanding enantioselectivities are closely related to the specific stereochemical microenvironment provided by the arrangement of the amphiphiles in the supramolecular assembly. Based on the experimental evidence of chirality transfer from supramolecular nanohelices to coordinated Cu(II) and substrate aza-chalcone and the molecular dynamics simulations, the enantioselective catalytic mechanisms are proposed. Moreover, the relationships between molecular structures of amino acid amphiphiles (the hydrophilic head group and hydrophobic alkyl chain length) in supramolecular catalysts and enantioselectivity in Diels-Alder reactions are elaborated.

Chiral Quantum Materials: When Chemistry Meets Physics.

Chirality is a fundamental property of nature with relevance in biochemistry and physics, particularly in the field of catalysis. Understanding the mechanisms underlying chirality transfer is crucial for advancing the knowledge of chiral-related catalysis. Chiral quantum materials with intriguing chirality-dependent electronic properties, such as spin-orbital coupling (SOC) and exotic spin/orbital angular momentum (SAM/OAM), open novel avenues for linking solid-state topologies with chiral catalysis. In this review, the growth of topological homochiral crystals (THCs) is described, and their applications in heterogeneous catalysis, including hydrogen evolution reaction (HER), oxygen electrocatalysis, and asymmetric catalysis are summarized. A possible link between chirality-dependent electronic properties and heterogeneous catalysis is discussed. Finally, existing challenges in this field are highlighted, and a brief outlook on the impact of THCs on the overarching chemical-physical research is presented.

Unraveling Dynamic Helicity Inversion and Chirality Transfer through the Synthesis of Discrete Azobenzene Oligomers by an Iterative Exponential Growth Strategy.

Unraveling the chirality transfer mechanism of polymer assemblies and controlling their handedness is beneficial for exploring the origin of hierarchical chirality and developing smart materials with desired chiroptical activities. However, polydisperse polymers often lead to an ambiguous or statistical evaluation of the structure-property relationship, and it remains unclear how the iterative number of repeating units function in the helicity inversion of polymer assemblies. Herein, we report the macroscopic helicity and dynamic manipulation of the chiroptical activity of supramolecular assemblies from discrete azobenzene-containing oligomers (azooligomers), together with the helicity inversion and morphological transition achieved solely by changing the iterative chain lengths. The corresponding assemblies also differ from their polydisperse counterparts in terms of thermodynamic properties, chiroptical activities, and morphological control.

Unraveling Dynamic Helicity Inversion and Chirality Transfer through the Synthesis of Discrete Azobenzene Oligomers by an Iterative Exponential Growth Strategy

AbstractUnraveling the chirality transfer mechanism of polymer assemblies and controlling their handedness is beneficial for exploring the origin of hierarchical chirality and developing smart materials with desired chiroptical activities. However, polydisperse polymers often lead to an ambiguous or statistical evaluation of the structure–property relationship, and it remains unclear how the iterative number of repeating units function in the helicity inversion of polymer assemblies. Herein, we report the macroscopic helicity and dynamic manipulation of the chiroptical activity of supramolecular assemblies from discrete azobenzene‐containing oligomers (azooligomers), together with the helicity inversion and morphological transition achieved solely by changing the iterative chain lengths. The corresponding assemblies also differ from their polydisperse counterparts in terms of thermodynamic properties, chiroptical activities, and morphological control.

Asymmetric Two‐Component Alkenyl Catellani Reaction for the Construction of C—N Axial Chirality†

Comprehensive SummaryHerein, we report an asymmetric two‐component alkenyl Catellani reaction for the construction of C—N axial chirality through a palladium/chiral norbornene cooperative catalysis and an axial‐to‐axial chirality transfer process. Various partially aromatic iodinated 2‐pyridones, quinolones, coumarin and uracil substrates react with 2,6‐disubstituted aryl bromides with a tethered amide group, to afford a wide variety of polycyclic C—N atropisomers (38 examples, up to 97% e.e.). The obtained C—N axial chirality originates from the preformed transient C—C axial chirality with high fidelity. The synthetic utility of this chemistry is demonstrated by facile preparation of complex quinoline and pyridine based C—N atropisomers through a N‐deprotection and aromatization sequence. In addition, a remote axial‐to‐central diastereoinduction process dictated by C—N axial chirality is observed with excellent diastereocontrol.

Aqueous Circularly Polarized Luminescence Induced by Homopolypeptide Self-Assembly.

Remarkable advances have been achieved in solution self-assembly of polypeptides from the perspective of nanostructures, mechanisms, and applications. Despite the intrinsic chirality of polypeptides, the promising generation of aqueous circularly polarized luminescence (CPL) based on their self-assembly has been rarely reported due to the weak fluorescence of most polypeptides and the indeterminate self-assembly mechanism. Here, we propose a facile strategy for achieving aqueous CPL based on the self-assembly of simple homopolypeptides modified with a terminal group featuring both twisted intramolecular charge transfer and aggregation-induced emission properties. A morphology-dependent CPL can be observed under different self-assembly conditions by altering the solvents. A nanotoroid-dispersed aqueous solution with detectable CPL can be obtained by using tetrahydrofuran as a good solvent for the self-assembly, which is attributed to the involvement of the terminal group in the chiral environment formed by the homopolypeptide chains. However, such a chiral packing mode cannot be realized in nanorods self-assembled from dioxane, resulting in an inactive CPL phenomenon. Furthermore, CPL signals can be greatly amplified by co-assembly of homopolypeptides with the achiral small molecule derived from the terminal group. This work not only provides a pathway to construct aqueous CPL-active homopolypeptide nanomaterials but also reveals a potential mechanism in the self-assembly for chiral production, transfer, and amplification in polypeptide-based nanostructures.

Asymmetric Cycloaddition Reactions of Aryne Intermediates with a Chiral Carbon-Carbon Axis: Syntheses of Axially Chiral Biaryl Compounds.

An asymmetric synthesis via an axially chiral arylaryne intermediate was developed. A cycloaddition reaction with various arynophiles was used to obtain chiral biaryl compounds while preserving the enantiomeric excess (ee) of a precursor even though the reaction proceeds through an arylaryne intermediate, whose chirality decreases on a time-dependent basis. High chiral transfer from a precursor to a product was observed not only at low temperature (-78 °C) but also at room temperature.

Alkene versus Aryl Chlorination in Asymmetric Hypervalent Iodine Catalysis: A Case Study

AbstractHypervalent λ3-iodanes have become a prominent tool for halofunctionalizations of alkenes. Despite many examples of asymmetric fluorinations reported lately, the corresponding enantioselective chlorination reactions using iodoresorcinol-based catalysts are significantly less developed, with only one example known to date. Here, we show how competing aromatic chlorination of the iodoarene catalyst is a significant obstacle in these transformations, hinting towards a conceptual issue with this well-established catalyst class for enantioselective chlorinations. Consequently, the reaction conditions and the catalyst design must be adapted to facilitate an effective chirality transfer. Hence, attention should be paid when selecting the oxidizing agent, the stoichiometry, and careful reaction analysis must be conducted to identify the factual catalytically active species.

Iron-Promoted 1,5-Substitution Reaction of Endocyclic Enyne Oxiranes with MeMgBr: A Stereoselective Method for the Synthesis of Exocyclic 2,4,5-Trienol Derivatives

The iron-promoted 1,5-substitution reaction of endocyclic oxiranes with MeMgBr yields exocyclic 2,4,5-trienols with high diastereomeric ratios of up to 100:0. However, for the method’s success, the oxirane ring must have a trans-configuration. The reactions exhibit strong stereoselectivity concerning the methylation mode and the configuration of the resulting exocyclic double bond. Enantiomerically pure enyne oxiranes can be synthesized through Sharpless asymmetric dihydroxylation and subsequent manipulations. With these reagents, it has been possible to produce exocyclic 2,4,5-trienols in enantiopure forms. Importantly, this process maintains chirality without degradation during the center-to-axis transfer of chirality.

Remote Enantioselective Epoxidation Reactions Catalyzed by Chiral Iron Porphyrin Complexes with a Hydrogen-Bonding Site

AbstractIron porphyrin complexes, which were linked via a para-phenylethynyl group to a chiral scaffold with a lactam binding site, were probed as catalysts in the enantioselective epoxidation of 4-(ω-alkenyl)-quinolones. It was found that the 3-butenyl group in the substrate accounts for the highest enantioselectivity (up to 44% ee) and the absolute configuration of an oxirane product was elucidated by electron diffraction. A two-point hydrogen bond of the substrate to the catalyst is likely responsible for enantioface differentiation at a remote position. The study shows chirality transfer to be possible via four nonstereogenic carbon atoms between the binding site of the substrate and its reactive C=C double bond.

Rhodium(I)‐Catalyzed Asymmetric Hydroarylative Cyclization of 1,6‐Diynes to Access Atropisomerically Labile Chiral Dienes

AbstractAxially chiral open‐chained olefins are an underexplored class of atropisomers, whose enantioselective synthesis represents a daunting challenge due to their relatively low racemization barrier. We herein report rhodium(I)‐catalyzed hydroarylative cyclization of 1,6‐diynes with three distinct classes of arenes, enabling highly enantioselective synthesis of a broad range of axially chiral 1,3‐dienes that are conformationally labile (ΔG≠(rac)=26.6–28.0 kcal/mol). The coupling reactions in each category proceeded with excellent enantioselectivity, regioselectivity, and Z/E selectivity under mild reaction conditions. Computational studies of the coupling of quinoline N‐oxide system reveal that the reaction proceeds via initial oxidative cyclization of the 1,6‐diyne to give a rhodacyclic intermediate, followed by σ‐bond metathesis between the arene C−H bond and the Rh−C(vinyl) bond, with subsequent C−C reductive elimination being enantio‐determining and turnover‐limiting. The DFT‐established mechanism is consistent with the experimental studies. The coupled products of quinoline N‐oxides undergo facile visible light‐induced intramolecular oxygen‐atom transfer, affording chiral epoxides with complete axial‐to‐central chirality transfer.

Rhodium(I)-Catalyzed Asymmetric Hydroarylative Cyclization of 1,6-Diynes to Access Atropisomerically Labile Chiral Dienes.

Axially chiral open-chained olefins are an underexplored class of atropisomers, whose enantioselective synthesis represents a daunting challenge due to their relatively low racemization barrier. We herein report rhodium(I)-catalyzed hydroarylative cyclization of 1,6-diynes with three distinct classes of arenes, enabling highly enantioselective synthesis of a broad range of axially chiral 1,3-dienes that are conformationally labile (ΔG≠ (rac)=26.6-28.0 kcal/mol). The coupling reactions in each category proceeded with excellent enantioselectivity, regioselectivity, and Z/E selectivity under mild reaction conditions. Computational studies of the coupling of quinoline N-oxide system reveal that the reaction proceeds via initial oxidative cyclization of the 1,6-diyne to give a rhodacyclic intermediate, followed by σ-bond metathesis between the arene C-H bond and the Rh-C(vinyl) bond, with subsequent C-C reductive elimination being enantio-determining and turnover-limiting. The DFT-established mechanism is consistent with the experimental studies. The coupled products of quinoline N-oxides undergo facile visible light-induced intramolecular oxygen-atom transfer, affording chiral epoxides with complete axial-to-central chirality transfer.

Chiral CuxOS@Fe‐MOFs for Enhanced Cancer Therapy

AbstractHere, the development of chiral D‐/L‐CuxOS nanoparticle‐engineered metal–organic frameworks (Fe‐MIL‐88B‐NH2), denoted as D‐/L‐CuxOS@Fe‐MOFs, for cuproptosis and ferroptosis synergistic therapy is described. The D‐/L‐CuxOS@Fe‐MOF displayed intense circular dichroism (CD) bands at 488 nm due to the chirality transfer from chiral penicillamine ligands. Chiral D‐/L‐CuxOS@Fe‐MOF showed tumor microenvironment‐triggered catalytic therapeutic activity by simultaneously depleting L‐glutathione (GSH) and generating potent reactive oxygen species in cancer cells. In vivo experimental results synchronously demonstrated D‐CuxOS@Fe‐MOF with higher efficiency of cancer therapy. The findings revealed that copper/iron ions released from chiral D‐CuxOS@Fe‐MOF induced augmented oxidative stress and potent ferroptosis, which synergizes with cuproptosis for enhanced cancer therapy. The synergistic index for D‐CuxOS@Fe‐MOF is determined to be 1.94, while L‐CuxOS@Fe‐MOF and D,L‐CuxOS@Fe‐MOF with 1.75 and 1.84, respectively. To the best of the knowledge, this is the first report of a chiral nanomaterial capable of inducing synergistic ferroptosis‐cuproptosis therapy for cancers. The results should invigorate studies pursuing the rational design of chiral nanomaterials for efficacious cancer therapy based on cuproptosis and ferroptosis.

Exciton Chirality Transfer Empowers Self-Triggered Spin-Polarized Amplified Spontaneous Emission from 1D-Anchoring-3D Perovskites.

Spin-polarized lasers, arising from stimulated emission of imbalanced spin populations, play a vital role in spin-optoelectronics.It is usually tackled by external spin injection, inevitably suffering from additional losses across the barriers from injection sources to gain materials. Herein, spin-polarized coherent light emission is self-triggered from the 1D-anchoring-3D perovskites, where the imbalanced populations in achiral 3D perovskites are endowed with the spin selectivity of exciton chirality (EC) underpinned by chiral 1D perovskites. Efficient transfer of EC is enabled by rapid energy transfer, thereby creating an imbalance of the spin population of excited states. Stimulated emission of such populations brings self-triggered spin-polarized amplified spontaneous emission in the composite perovskites, yielding a higher degree of polarization (DOP) than that based on optical spin injection into bare achiral 3D perovskites. Chemical diversity of composite perovskites not only enables to adjust band gap for broadband output of spin-polarized lightsignals but also promises to manipulate radiative decay and spin relaxation toward remarkably increased DOP. These results highlight the importance of EC transfer mechanism for spin-polarized lasing and represent a crucial step toward the development of chiral-spintronics.

The effect of shape, polydispersity, charge, and fraction of crystallite bundles on the cholesteric pitch of cellulose nanocrystal suspensions

Using Onsager–Straley’s second-virial theory, we investigate the cholesteric pitch of cellulose nanocrystal (CNC) suspensions. We model the CNCs as hard chiral bundles of microfibrils and examine the effect of the shape of these chiral bundles, characterized by aspect ratio and chirality, on the cholesteric pitch. Additionally, we explore the impact of length polydispersity and surface charge on the cholesteric phase of CNCs. Furthermore, we consider binary mixtures of twisted bundles and achiral primary crystallites to provide a more realistic representation of CNC suspensions. Our findings reveal that the degree of bundle twisting significantly affects the helical twisting of the cholesteric phase. We also observe that the average particle length and length polydispersity have substantial effects on strongly twisted bundles but minimal effects on weakly twisted ones. Finally, our study indicates that as the range of electrostatic interactions increases, the transfer of chirality from the microscopic to macroscopic length scales becomes masked, resulting in an increase in the cholesteric pitch. In the case of binary mixtures, the bundles act as chiral dopants, and an increasing fraction of bundles progressively enhances the helical twisting of the cholesteric phase.

Iron-catalyzed regio- and stereoselective substitution of 2,4-alkadienyl carboxylates with aryl Grignard reagents

Treatment of 2,4-alkadienyl carboxylates with an aryl Grignard reagent in the presence of a catalytic amount of FeCl2 affords diene derivatives in high yields with regio- and cis-stereoselectivity. Additionally, optically active 2,4-alkadienyl carboxylates afford the corresponding optically active dienes in high yields and with excellent degrees of chiral transfer. More importantly, the absolute structures of both starting material and product clarified the stereochemical pathway.

Supramolecular gelators enabling chiral organogels for naked-eye enantiodifferentiation with wide accessibility and applicability

Techniques to acquire chiral information from molecules are essential for deciphering important biological processes and improving the performance of industrial chiral materials. Herein, we report novel supramolecular gelators that enable widely accessible chiral supramolecular organogels for simple naked-eye enantiodifferentiation of specific enantiomers (left- or right-handedness) for wide-range substances. The supramolecular gelators featuring multiple hydrogen-bonding sites and large π-π conjugated groups are produced by complexing commercially available chiral tartaric acids and achiral 1-naphthylmethylamine. The highly polar and insoluble acid-amine complexes drive the aggregation of the supramolecular gelators, which further form chiral nanofibers due to chirality transfer from tartaric acid to the supramolecular nanofibers through multiple hydrogen-bonding between the hydroxyl groups of chiral tartaric acids and π-π stacking between 1-naphthylmethylamine molecules. At high concentrations, physical crosslinking of the chiral nanofibers creates a chiral gel structure that facilitates interactions between its chirally and non-covalently associated components and enantiomers, making the gel system particularly sensitive to specific types of enantiomers. Consequently, sensitive naked-eye detection of specific enantiomers of diverse substances is achieved via observing “gel-to-micelle” transitions, which occurs when the enantiomers generate complexes that disrupt chirality transfer in the co-assembly and destroy the hierarchical structures.