Chirality Control Research Articles

En Route to High-Density Chiral Single-walled Carbon Nanotube Arrays using Solid Trojan Catalysts.

Solid catalyst is widely recognized as an effective strategy to control the chirality of single-walled carbon nanotubes (SWNTs). However, it is still not compatible with high density in horizontal arrays. "Trojan" catalysts strategy is one of the most effective methods to realize SWNTs with high density and has great potential in chirality control. Here, the co-realization of high density and chirality controlling for SWNTs in a low-temperature growth process is reported based on the developed solid "Trojan" catalyst. High temperature "Trojan" catalyst formation process provides sufficient catalyst number to acquire high density. These liquid "Trojan" catalysts are cooled to solid state by adopting low growth temperature (540°C), which can be good template to realize the chirality controlling of SWNTs with exposing six-fold symmetry face, (111). Finally, (9, 6) and (13, 1) SWNTs enriched horizontal array with the purity of ≈90% and density of 4tubesµm-1 is realized. The comparison between the distribution of initial catalysts and the density of as-grown tubes indicates no sacrificing on catalysts number to improve chirality selectivity. This work opens a new avenue on the catalyst's design and chirality controlling in SWNTs growth.

Phosphoric Acid‐Catalyzed Enantioselective Synthesis of Axially Chiral Anthrone‐based Compounds

AbstractAnthrones and analogues are structural cores shared by diverse pharmacologically active natural and synthetic compounds. The sp2‐rich nature imposes inherent obstruction to introduce stereogenic element onto the tricyclic aromatic backbone. In our pursuit to expand the chemical space of axial chirality, a novel type of axially chiral anthrone‐derived skeleton was discovered. This work establishes oxime ether as suitable functionality to furnish axial chirality on symmetric anthrone skeletons through stereoselective condensation of the carbonyl entity with long‐range chirality control. The enantioenriched anthrones could be elaborated into dibenzo‐fused seven‐membered N‐heterocycles containing well‐defined stereogenic center via Beckmann rearrangement with axial‐to‐point chirality conversion.

Phosphoric Acid-Catalyzed Enantioselective Synthesis of Axially Chiral Anthrone-based Compounds.

Anthrones and analogues are structural cores shared by diverse pharmacologically active natural and synthetic compounds. The sp2 -rich nature imposes inherent obstruction to introduce stereogenic element onto the tricyclic aromatic backbone. In our pursuit to expand the chemical space of axial chirality, a novel type of axially chiral anthrone-derived skeleton was discovered. This work establishes oxime ether as suitable functionality to furnish axial chirality on symmetric anthrone skeletons through stereoselective condensation of the carbonyl entity with long-range chirality control. The enantioenriched anthrones could be elaborated into dibenzo-fused seven-membered N-heterocycles containing well-defined stereogenic center via Beckmann rearrangement with axial-to-point chirality conversion.

Are the mRNA vaccines inducing the Sanarelli-Shwartzman phenomenon?

Adverse events of myocarditis, pericarditis, and thrombosis, temporally associated with mRNA vaccination(s) and/or mRNA vaccine boosters, have been reported during post-marketing safety surveillance in the U.S. CDC VAERS database and 2021 CDC guidance to physicians. An interim report unexpectedly revealed inflammatory biomarker elevations in vaccine recipients. During review of considerable published research on the Sanarelli-Shwartzman phenomenon (SSP) and the use of nucleic acids as vaccine adjuvants, a novel, hypothesis is proposed. Even today, after being studied for over a century, the pathophysiology of the SSP is not fully understood. Motivated by a paper from 1950, titled “General Adaptation Syndrome” by Hans Selye, and recent published research by Korean investigators, a novel, non-conventional hypothesis was generated. Gluten and lectin sensitivity are cited as examples of sensitizing events of the SSP, for which we propose ensemble hydrophobic chiroptical catalysis may have therapeutic benefit. Under the ensemble HCC hypothesis, we propose that inflammatory stress and scurvy promote loss of chirality control, anomeric fidelity, phenotypic stability, and immune function, both humoral and cell-mediated, with the dialyzable transfer factor, L-ascorbic acid, and spin water playing central roles. It is proposed that therapeutic synergy of L-ascorbic acid, bioflavonoids, and corticosteroids in countering the SARS-CoV-2 pathogen arises from memory of chirality which originated during their biosynthesis. It is proposed that ensemble HCC is powered by radiant and or zero-point energy (quantum vacuum fluctuations) which may support a paradigm shift to supramolecular biology. The distinction between supramolecular biology and supramolecular xenobiology is highlighted.

Affecting the structure of skyrmions using ferromagnetic nanodisks with inhomogeneous properties: switching skyrmion helicity and polarity

The topological stability of skyrmions is an important element for using these objects in new technologies such as skyrmionics, spintronics, and so on. Indeed, this kind of stability keeps a skyrmion’s structure as unbending, shielding the information that, by chance, it could carry. On the other hand, a controlled manipulation of skyrmion configuration could be an extra ingredient for technological applications. It is not an easy task and, particularly, the control of skyrmion polarity and chirality (for Bloch-type) and helicity (for Néel-type) may be important in this direction. Here, we investigate the skyrmion oscillatory motion in a hybrid nanodisk by using atomistic spin dynamics simulations. If a skyrmion is made to oscillate in a disk formed by two different materials with opposite Dzyaloshinskii–Moriya interactions (), then its helicity experiences an inversion. Nonetheless, if the skyrmion oscillations occur in a homogeneous disk submitted to opposite magnetic fields in distinct regions (for instance, semi-disks 1 and 2), the skyrmion polarity and helicity suffer an inversion. Such skyrmionic-oscillators could provide a dynamical degree of freedom, yielding new functionalities to skyrmion-based logic devices.

Hierarchically self-assembled homochiral helical microtoroids

Fabricating microscale helical structures from small molecules remains challenging due to the disfavoured torsion energy of twisted architectures and elusory chirality control at different hierarchical levels of assemblies. Here we report a combined solution–interface-directed assembly strategy for the formation of hierarchically self-assembled helical microtoroids with micrometre-scale lengths. A drop-evaporation assembly protocol on a solid substrate from pre-assembled intermediate colloids of enantiomeric binaphthalene bisurea compounds leads to microtoroids with preferred helicity, which depends on the molecular chirality of the starting enantiomers. Collective variable-temperature spectroscopic analyses, electron microscopy characterizations and theoretical simulations reveal a mechanism that simultaneously induces aggregation and cyclization to impart a favourable handedness to the final microtoroidal structures. We then use monodispersed luminescent helical toroids as chiral light-harvesting antenna and show excellent Förster resonance energy transfer ability to a co-hosted chiral acceptor dye, leading to unique circularly polarized luminescence. Our results shed light on the potential of the combined solution–interface-directed self-assembly approach in directing hierarchical chirality control and may advance the prospect of chiral superstructures at a higher length scale.

Gold-Nanoparticle-Based Chiral Plasmonic Nanostructures and Their Biomedical Applications.

As chiral antennas, plasmonic nanoparticles (NPs) can enhance chiral responses of chiral materials by forming hybrid structures and improving their own chirality preference as well. Chirality-dependent properties of plasmonic NPs broaden application potentials of chiral nanostructures in the biomedical field. Herein, we review the wet-chemical synthesis and self-assembly fabrication of gold-NP-based chiral nanostructures. Discrete chiral NPs are mainly obtained via the seed-mediated growth of achiral gold NPs under the guide of chiral molecules during growth. Irradiation with chiral light during growth is demonstrated to be a promising method for chirality control. Chiral assemblies are fabricated via the bottom-up assembly of achiral gold NPs using chiral linkers or guided by chiral templates, which exhibit large chiroplasmonic activities. In describing recent advances, emphasis is placed on the design and synthesis of chiral nanostructures with the tuning and amplification of plasmonic circular dichroism responses. In addition, the review discusses the most recent or even emerging trends in biomedical fields from biosensing and imaging to disease diagnosis and therapy.

New Trends in the Quality Control of Enantiomeric Drugs: Quality by Design-Compliant Development of Chiral Capillary Electrophoresis Methods.

Capillary electrophoresis (CE) is a potent method for analyzing chiral substances and is commonly used in the enantioseparation and chiral purity control of pharmaceuticals from different matrices. The adoption of Quality by Design (QbD) concepts in analytical method development, optimization and validation is a widespread trend observed in various analytical approaches including chiral CE. The application of Analytical QbD (AQbD) leads to the development of analytical methods based on sound science combined with risk management, and to a well understood process clarifying the influence of method parameters on the analytical output. The Design of Experiments (DoE) method employing chemometric tools is an essential part of QbD-based method development, allowing for the simultaneous evaluation of experimental parameters as well as their interaction. In 2022 the International Council for Harmonization (ICH) released two draft guidelines (ICH Q14 and ICH Q2(R2)) that are intended to encourage more robust analytical procedures. The ICH Q14 guideline intends to harmonize the scientific approaches for analytical procedures’ development, while the Q2(R2) document covers the validation principles for the use of analytical procedures including the recent applications that require multivariate statistical analyses. The aim of this review is to provide an overview of the new prospects for chiral CE method development applied for the enantiomeric purity control of pharmaceuticals using AQbD principles. The review also provides an overview of recent research (2012–2022) on the applicability of CE methods in chiral drug impurity profiling.

Nucleation of Single-Wall Carbon Nanotubes from Faceted Pt Catalyst Particles Revealed by in Situ Transmission Electron Microscopy.

Revealing the nucleation and growth mechanism of single-wall carbon nanotubes (SWCNTs) from faceted solid catalysts is crucial to the control of their structure and properties. However, due to the small size and complex growth environment, the early stages and dynamic process of SWCNT nucleation have rarely been directly revealed, especially under atmospheric conditions. Here, we report the atomic-resolved nucleation of SWCNTs from the faces of truncated octahedral Pt catalysts under atmospheric pressure using a transmission electron microscope equipped with a gas-cell. It was found that the graphene layers were initially formed preferentially on (111) surfaces, which then joined together to form an annular belt and a hemispherical cap, followed by the elongation of the SWCNT. Based on the observations, an annular belt assembly nucleation model and a possible chirality control mechanism are proposed for SWCNTs grown from well-faceted Pt catalysts, which provides useful guidance for the controlled synthesis of SWCNTs by catalyst design.

Self-induced transparency in a perfectly absorbing chiral second-harmonic generator

Transparency and perfect absorption are two contradictory terms; a perfect absorber never permits waves to transmit through. However, this statement only remains true in the linear regime, where the nonlinearity has been omitted and the physical system like the perfect absorber is not affected by the incoming waves. Here we experimentally demonstrate an intriguing self-induced transparency effect in a perfectly absorbing optical microcavity, which perfectly absorbs any incoming waves at the low power level, but allows a portion of waves to be transmitted at the higher power due to the nonlinear coupling between the fundamental and its second harmonic modes. Moreover, the asymmetric scattering nature of the microcavity enables a chiral and unidirectional reflection in one of the input ports, this leads to asymmetric and chiral coherent control of the perfect absorption states through phase varying. More importantly, such chiral behaviors also empower the chiral emission of second-harmonic generation with a high distinct ratio in the transparency state. These results pave the way for controllable transparency in a wide range of fields in optics, microwaves, acoustics, mechanics, and matter waves.

Remote Control of Dynamic Twistacene Chirality.

We report a reliable way to manipulate the dynamic, axial chirality in perylene diimide (PDI)-based twistacenes. Specifically, we reveal how chiral substituents on the imide position induce the helicity in a series of PDI-based twistacenes. We demonstrate that this remote chirality is able to control the helicity of flexible [4]helicene subunits by UV-vis, CD spectroscopy, X-ray crystallography, and TDDFT calculations. Furthermore, we have discovered that both the chiral substituent and the solvent each has a strong impact on the sign and intensity of the CD signals, highlighting the control of the dynamic helicity in this flexible system. DFT calculations suggest that the steric interaction of the chiral substituents is the important factor in how well a particular group is at inducing a preferred helicity.

Practical Asymmetric Synthesis of a Bicyclic Pyrrolidinol

The “butterfly-shaped” bicyclic pyrrolidinol ((2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl)-methanol (1) is a key building block for drug candidates, and its practical chemical synthesis remains elusive. As such, an asymmetric synthesis for ((2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl)-methanol (1) that is amenable for scale-up has been developed. The newly optimized process utilizes readily available N-Boc-trans-4-hydroxy-l-proline methyl ester (8) to establish the challenging stereogenic center bearing the fluoride. Subsequent diastereoselective α-alkylation was achieved by leveraging Seebach’s self-regeneration of stereochemistry (SRS) methodology, which has been exploited for the synthesis of proline derivatives. Finally, intramolecular cyclization/deprotection cascade and carbonyl reduction afford the bicyclic pyrrolidinol 1 in nine linear steps from compound 8. This process significantly reduces the overall production sequence and allows the preparation of product 1 on a multikilo scale with a 40% overall yield and perfect control of chirality (>99% ee and de).

On-demand design based on deep learning and phase manipulation of all-silicon terahertz chiral metasurfaces

Chiral metasurfaces have been widely used in sensing, imaging and other fields because they can manipulate light through the efficient circular dichroism (CD). However, its on-demand design is still a very challenging task. In this work, we propose an on-demand multiple reverse design based on deep learning, named target-driven conditional generative network (TCGN). It can reverse design the metasurface structure that meets the required CD, and its mean square error (MAE) is 0.0089. We use this method to inversely design multiple sets of metasurfaces with different structures, and all their CD values can exceed 0.36. Both simulations and experiments prove the feasibility and effectiveness of using deep learning to reverse design metasurfaces. In addition, the designed metasurface can realize chiral wavefront control under dual frequency. This design method based on deep learning can rapidly and efficiently design the chiral metasurfaces, which provides a new way for the design of metasurfaces.

Global polarity and chirality control of an active fluid by a passive nematic material (Nat Mat)

Global polarity and chirality control of an active fluid by a passive nematic material (Nat Mat)

Gate-controlled skyrmion and domain wall chirality

Magnetic skyrmions are localized chiral spin textures, which offer great promise to store and process information at the nanoscale. In the presence of asymmetric exchange interactions, their chirality, which governs their dynamics, is generally considered as an intrinsic parameter set during the sample deposition. In this work, we experimentally demonstrate that a gate voltage can control this key parameter. We probe the chirality of skyrmions and chiral domain walls by observing the direction of their current-induced motion and show that a gate voltage can reverse it. This local and dynamical reversal of the chirality is due to a sign inversion of the interfacial Dzyaloshinskii-Moriya interaction that we attribute to ionic migration of oxygen under gate voltage. Micromagnetic simulations show that the chirality reversal is a continuous transformation, in which the skyrmion is conserved. This control of chirality with 2–3 V gate voltage can be used for skyrmion-based logic devices, yielding new functionalities.

Social Self-Sorting Synthesis of Molecular Knots.

We report the synthesis of molecular prime and composite knots by social self-sorting of 2,6-pyridinedicarboxamide (pdc) ligands of differing topicity and stereochemistry. Upon mixing achiral monotopic and ditopic pdc-ligand strands in a 1:1:1 ratio with Lu(III), a well-defined heteromeric complex featuring one of each ligand strand and the metal ion is selectively formed. Introducing point-chiral centers into the ligands leads to single-sense helical stereochemistry of the resulting coordination complex. Covalent capture of the entangled structure by ring-closing olefin metathesis then gives a socially self-sorted trefoil knot of single topological handedness. In a related manner, a heteromeric molecular granny knot (a six-crossing composite knot featuring two trefoil tangles of the same handedness) was assembled from social self-sorting of ditopic and tetratopic multi-pdc strands. A molecular square knot (a six-crossing composite knot of two trefoil tangles of opposite handedness) was assembled by social self-sorting of a ditopic pdc strand with four (S)-centers and a tetratopic strand with two (S)- and six (R)-centers. Each of the entangled structures was characterized by 1H and 13C NMR spectroscopy, mass spectrometry, and circular dichroism spectroscopy. The precise control of composition and topological chirality through social self-sorting enables the rapid assembly of well-defined sequences of entanglements for molecular knots.

Reliable control of magnetic vortex chirality in asymmetrically optimized magnetic nanodisk

Magnetic vortex has attracted attention in the field of information storage because their topological spin structures with chiral bistable states. If the vortex core polarity and vortex circulation sense can be controlled simultaneously in a nanodisk, which will be more beneficial to realize the multi-bit ultrahigh density storage. In this paper, a reliable control scheme for magnetic vortex chirality is proposed by optimizing the structure of Pac-Man-like nanodisk. The results show that the polarity and circulation of the vortex can be controlled simultaneously by changing the direction of the global magnetic field, and even the chiral states of the vortex can be determined by detecting the stray field distribution on the surface of the nanodisk. The optimized Pac-Man-like nanodisk provide an experimental method for the control and detection of magnetic vortex chirality, which will be beneficial to the realization of multi-bit magnetic storage or magnetic logic technology in the future.

Kinetic Resolution Approach to the Synthesis of C-N Axially Chiral N-Aryl Aminomaleimides via NHC-Catalyzed [3 + 3] Annulation.

Chiral NHC-catalyzed kinetic resolution of N-aryl aminomaleimides allowing the synthesis of C-N axially chiral N-aryl aminomaleimides via remote chirality control is presented. The catalytically generated α,β-unsaturated acylazoliums from 2-bromoenals underwent selective [3 + 3] annulation with one of the enantiomers of maleimide to furnish fused-dihydropyridinone (bearing axial/central chirality, up to 6:1 dr, >99:1 er) leaving the enantioenriched opposite enantiomer (up to >99:1 er). Studies on C-N bond rotation barrier and dependence on temperature are also provided.

Self‐Regulated Pathway‐Dependent Chirality Control of Silver Nanoclusters

AbstractImparting chirality affords additive values, functions and responsiveness in molecular systems including nanoscale materials. Here, we report pathway‐dependent chirality control in silver nanoclusters (NCs). The use of enantiomeric ligand, α‐dihydrolipoic acid (DHLA), for the synthesis of Ag NCs leads to the preferential formation of one‐handed chiral Ag29(DHLA)12 NCs with intrinsic chirality in the exterior shell composed of a silver‐dithiolate framework. Small Lewis base molecules such as pyridine bind to silver atoms in the shell of NC as a guest. The guest binding reverses the relative stability between the right‐ and left‐handed NCs upon a steric interaction with the chiral ligand DHLA in the exterior shell in a kinetic manner, leading to unprecedented chirality inversion in the synthesis of NCs. This mechanism is further extended to the self‐regulation or self‐replication of chirality through interNC interactions dependent on the concentration in the synthesis of NCs.

Self-Regulated Pathway-Dependent Chirality Control of Silver Nanoclusters.

Imparting chirality affords additive values, functions and responsiveness in molecular systems including nanoscale materials. Here, we report pathway-dependent chirality control in silver nanoclusters (NCs). The use of enantiomeric ligand, α-dihydrolipoic acid (DHLA), for the synthesis of Ag NCs leads to the preferential formation of one-handed chiral Ag29 (DHLA)12 NCs with intrinsic chirality in the exterior shell composed of a silver-dithiolate framework. Small Lewis base molecules such as pyridine bind to silver atoms in the shell of NC as a guest. The guest binding reverses the relative stability between the right- and left-handed NCs upon a steric interaction with the chiral ligand DHLA in the exterior shell in a kinetic manner, leading to unprecedented chirality inversion in the synthesis of NCs. This mechanism is further extended to the self-regulation or self-replication of chirality through interNC interactions dependent on the concentration in the synthesis of NCs.