Tapered chiral nanoparticles as broad-spectrum thermally stable antivirals for SARS-CoV-2 variants.

The incessant mutations of viruses, variable immune responses, and likely emergence of new viral threats necessitate multiple approaches to novel antiviral therapeutics. Furthermore, the new antiviral agents should have broad-spectrum activity and be environmentally stable. Here, we show that biocompatible tapered CuS nanoparticles (NPs) efficiently agglutinate coronaviruses with binding affinity dependent on the chirality of surface ligands and particle shape. L-penicillamine-stabilized NPs with left-handed curved apexes display half-maximal inhibitory concentrations (IC50) as low as 0.66 pM (1.4 ng/mL) and 0.57 pM (1.2 ng/mL) for pseudo-type SARS-CoV-2 viruses and wild-type Wuhan-1 SARS-CoV-2 viruses, respectively, which are about 1,100 times lower than those for antibodies (0.73 nM). Benefiting from strong NPs-protein interactions, the same particles are also effective against other strains of coronaviruses, such as HCoV-HKU1, HCoV-OC43, HCoV-NL63, and SARS-CoV-2 Omicron variants with IC50 values below 10 pM (21.8 ng/mL). Considering rapid response to outbreaks, exposure to elevated temperatures causes no change in the antiviral activity of NPs while antibodies are completely deactivated. Testing in mice indicates that the chirality-optimized NPs can serve as thermally stable analogs of antiviral biologics complementing the current spectrum of treatments.

Unraveling the Origin of Reverse Plasmonic Circular Dichroism from Discrete Bichiral Au Nanoparticles.

Bichiral plasmonic nanoparticles exhibited intriguing geometry-dependent circular dichroism (CD) reversal; however, the crucial factor that dominates the plasmonic CD is still unclear. Combined with CD spectroscopy and theoretical multipole analysis, we demonstrate that plasmonic CD originates from the excitation of electric quadrupolar plasmons. Moreover, a comparative study of two distinct quadrupolar modes reveals the correlation between the sign of the CD and the local geometric handedness at the plasmonic hotspots, thereby establishing a structure-property relationship in bichiral nanoparticles. The reverse CD is attributed to the opposite directions of the wavelength shift of the two plasmon modes upon changing the particle geometry. By finely tuning the size of bichiral nanoparticles, we can further reveal that the dependence of plasmonic CD on the electric quadrupolar plasmons. Our work sheds light on the physical origin of plasmonic CD and provides important guidelines for the design of chiral plasmonic nanoparticles toward chirality-dependent applications.

Chiral Au-Pd Alloy Nanorods with Tunable Optical Chirality and Catalytically Active Surfaces.

Integrating the plasmonic chirality with excellent catalytic activities in plasmonic hybrid nanostructures provides a promising strategy to realize the chiral nanocatalysis toward many chemical reactions. However, the controllable synthesis of catalytically active chiral plasmonic nanoparticles with tailored geometries and compositions remains a significant challenge. Here it is demonstrated that chiral Au-Pd alloy nanorods with tunable optical chirality and catalytically active surfaces can be achieved by a seed-mediated coreduction growth method. Through manipulating the chiral inducers, Au nanorods selectively transform into two different intrinsically chiral Au-Pd alloy nanorods with distinct geometric chirality and tunable optical chirality. By further adjusting several key synthetic parameters, the optical chirality, composition, and geometry of the chiral Au-Pd nanorods are fine-tailored. More importantly, the chiral Au-Pd alloy nanorods exhibit appealing chiral catalytic activities as well as polarization-dependent plasmon-enhanced nanozyme catalytic activity, which has great potential for chiral nanocatalysis and plasmon-induced chiral photochemistry.

Tuning the Growth of Chiral Gold Nanoparticles Through Rational Design of a Chiral Molecular Inducer.

The bottom-up production of chiral gold nanomaterials holds great potential for the advancement of biosensing and nano-optics, among other applications. Reproducible preparations of colloidal nanomaterials with chiral morphology have been reported, using cosurfactants or chiral inducers such as thiolated amino acids. However, the underlying growth mechanisms for these nanomaterials remain insufficiently understood. We introduce herein a purposely devised chiral inducer, a cysteine modified with a hydrophobic chain, as a versatile chiral inducer. The amphiphilic and chiral features of this molecule provide control over the chiral morphology and the chiroptical signature of the obtained nanoparticles by simply varying the concentration of chiral inducer. These results are supported by circular dichroism and electromagnetic modeling as well as electron tomography to analyze structural evolution at the facet scale. Our observations suggest complex roles for the factors involved in chiral synthesis: the chemical nature of the chiral inducers and the influence of cosurfactants.

Tuning the Plexcitonic Optical Chirality Using Discrete Structurally Chiral Plasmonic Nanoparticles.

Constructing chiral plexcitonic systems with tunable plasmon-exciton coupling may advance the scientific exploitation of strong light-matter interactions. Because of their intriguing chiroptical properties, chiral plasmonic materials have shown promising applications in photonics, sensing, and biomedicine. However, the strong coupling of chiral plasmonic nanoparticles with excitons remains largely unexplored. Here we demonstrate the construction of a chiral plasmon-exciton system using chiral AuAg nanorods and J aggregates for tuning the plexcitonic optical chirality. Circular dichroism spectroscopy was employed to characterize chiral plasmon-exciton coupling, in which Rabi splitting and anticrossing behaviors were observed, whereas the extinction spectra exhibited less prominent phenomena. By controlling the number of molecular excitons and the energy detuning between plasmons and excitons, we have been able to fine-tune the plexcitonic optical chirality. The ability to fine-tune the plexcitonic optical chirality opens up unique opportunities for exploring chiral light-matter interactions and boosting the development of emerging chiroptical devices.

Site-Selective Chiral Growth of Anisotropic Au Triangular Nanoplates for Tuning the Optical Chirality.

Site-selective chiral growth of anisotropic nanoparticles is of great importance to realize the plasmonic nanostructures with delicate geometry and desired optical chirality; however, it remains largely unexplored. This work demonstrates a controlled site-selective chiral growth system based on the seed-mediated growth of anisotropic Au triangular nanoplates. The site-selective chiral growth involves two distinct underlying pathways, faceted growth and island growth, which are interswitchable upon maneuvering the interplay of chiral molecules, surfactants, and reducing agents. The pathway switch governs the geometric and chirality evolution of Au triangular nanoplates, giving rise to tailorable circular dichroism spectra. The ability to tune the optical chirality in a controlled manner by manipulating the site-selective chiral growth pathway opens up a promising strategy for exploiting chiral metamaterials with increasing architectural complexity in chiroptical applications.

Chiral Nanoparticles with Enhanced Thermal Stability of Chiral Structures through Alloying.

Metallic chiral nanoparticles (CNPs) promisingly function as asymmetric catalysts but lack an important study in thermal stability of optical activity that stems from metastable chiral lattices. In this work, annealing is applied to silver (Ag) CNPs, fabricated by glancing angle deposition (GLAD), and causes elimination of optical activity at 200 °C, mainly ascribed to chiral-to-achiral lattice transformation. The Ag CNPs are remarkedly enhanced in thermal stability through an alloying with aluminum (Al) via layer-by-layer GLAD to generate binary Ag0.5 Al0.5 CNPs composed of solid-state liquids, whose optical activity vanishes at 700 °C. Ease in the diffusion of Al atoms in the host Ag CNPs and thermal insulation from the Al2 O3 layers partially covering the binary CNPs effectively prohibit structural relaxation of the metastable chiral lattices, accounting for the significant enhancement in thermal stability of chiral lattices. This is a pioneering work to investigate the fundamental principles determining the thermal stability of metallic CNPs in terms of chiral structures and optical activity. It paves the way toward applying metallic CNPs to asymmetric catalysis at high temperature to accelerate an asymmetric synthesis of enantiomers with designable chirality, which is one of the most important topics in modern chemistry.

Nanohelix-Induced Optical Activity of Liquid Metal Nanoparticles.

Liquid metals (such as gallium or Ga) exist in liquid states under ambient conditions and are hardly sculpted in chiral structures. Herein, through electron-beam evaporation of Ga, hemispherical achiral Ga nanoparticles (NPs) are randomly immobilized along helical surfaces of SiO2 nanohelices (NHs), functioning as a chiral template. Helical assembly of Ga NPs shows chiroplasmonic optical activity owing to collective plasmon-plasmon interactions, which can be tuned as a function of a helical SiO2 pitch (P) and the amount of Ga evaporated. At a P of ≈150 nm, the chiroplasmonic optical activity, evaluated with anisotropic g-factor, can be as large as ≈0.1. Because the SiO2 NHs and Ga NPs have high environmental stability of nanostructures, the chiroplasmonic optical activity shows excellent anti-aging stability, despite slight blue shift and chiroplasmonic degradation for the first 2 weeks. Spontaneous oxidation of the Ga NPs enables the formation of dense Ga2 O3 layers covering Ga cores to prevent further oxidation and thus to stabilize the chiroplasmonic optical activity. This work devises an alternative approach to impose optical activity onto Ga NPs, providing an additional degree of freedom (i.e., chirality) for Ga-based flexible electronic devices to develop advanced applications of 3D display, circular polarizers, bio-imaging, and bio-detection.

Apple juice and red wine induced mirror-image circular dichroism in quantum dots.

Juices, wines, and extracts from plants contain high concentrations of various chiral compounds such as carboxylic acids or sugars. Several prior studies reported the synthesis of metallic and semiconducting nanoparticles relying on components of complex biological solutions. Herein, we present preparation of chiral CdS and CdSe quantum dots (QDs) using apple juice and red wine via phase transfer ligand exchange. Although both apple juice and red wine contain a complex mixture of chiral and achiral compounds, we have successfully used them for selective induction of predicted chiroptical properties and confirmed L-malic acid from the apple juice and L-tartaric acid from the red wine as the chiral inducers. This work illustrates the capability of using complex mixtures to construct chiral QDs with desired chiroptical properties as well as potential of QDs to selectively report a chiral molecule in a complex chiral mixture without the need for elaborate chiral recognition system.

Multilevel Chirality Transfer from Amino Acid Derivatives to Circularly Polarized Luminescence-Active Nanoparticles in Aqueous Medium.

Chirality at different levels is widely observed in nature, but the clue to connect it all together, and the way chirality transfers among different levels are still obscure. Herein, a l-/d-lysine-based self-assembly system was constructed, in which two-step chirality transfer among three different levels was observed in aqueous solution. The chirality originated from the point chirality of amino acid derivatives l-/d-PyLys hydrochloride, and was transferred to the planar conformational chirality of water-soluble pillar[5]arene pR-/pS-WP5. Then, with the aid of pR-/pS-WP5, nanoparticles were formed that exhibited L-/R-handed circularly polarized luminescence with a dissymmetry factor of up to ±0.001, arising from pyrene chiral excimers. This multilevel chirality transfer not only provides a perspective to trace potential clues, and to pursue certain ways by which the chirality transfers, but also offers a strategy to create controllable CPL emission in aqueous media.

Differential Interactions of Chiral Nanocapsules with DNA.

(1) Background: Chiral nanoparticular systems have recently emerged as a compelling platform for investigating stereospecific behavior at the nanoscopic level. We describe chiroselective supramolecular interactions that occur between DNA oligonucleotides and chiral polyurea nanocapsules. (2) Methods: We employ interfacial polyaddition reactions between toluene 2,4-diisocyanate and lysine enantiomers that occur in volatile oil-in-water nanoemulsions to synthesize hollow, solvent-free capsules with average sizes of approximately 300 nm and neutral surface potential. (3) Results: The resultant nanocapsules exhibit chiroptical activity and interact differentially with single stranded DNA oligonucleotides despite the lack of surface charge and, thus, the absence of significant electrostatic interactions. Preferential binding of DNA on D-polyurea nanocapsules compared to their L-counterparts is demonstrated by a fourfold increase in capsule size, a 50% higher rise in the absolute value of negative zeta potential (ζ-potential), and a three times lower free DNA concentration after equilibration with the excess of DNA. (4) Conclusions: We infer that the chirality of the novel polymeric nanocapsules affects their supramolecular interactions with DNA, possibly through modification of the surface morphology. These interactions can be exploited when developing carriers for gene therapy and theranostics. The resultant constructs are expected to be highly biocompatible due to their neutral potential and biodegradability of polyurea shells.

Chiral Ligand-Free, Optically Active Nanoparticles Inherently Composed of Chiral Lattices at the Atomic Scale.

Bulk metals lack chirality. Recently, metals have been sculptured with metastable chirality varying from the micro- to nano-scale. The manipulation of molecular chirality could be novelly performed using metals composed of chiral lattices at atomic scales (i.e., chiral nanoparticles or CNPs) if one could fundamentally understand the interactions between molecules and the chiral metal lattices. The incorporation of chiral ligands has been generally adapted to form metal CNPs. However, post-fabrication removal of chiral ligands usually causes relaxation of the metastable chiral lattices to thermodynamically stable achiral structures, and thus the coexisting chiral ligands will unavoidably disturb or screen the interactions of interest. Herein, a concept of metal CNPs that are free of chiral ligands and consist of atomically chiral lattices is introduced. Without chiral ligands, shear forces applied by substrate rotation along with the translation of incident atoms lead to imposing the metastable chiral lattices onto metals. Metal CNPs show not only the chiroptical effect but the enantiospecific interactions of chiral lattices and molecules. These two unique chiral effects have resulted in the applications of enantiodifferentiation and asymmetric synthesis. Prospectively, the extension in composition space and constituent engineering will apply alloy CNPs to enantiodiscrimination, enantioseperation, bio-imaging, bio-sensing, and asymmetric catalysis.

Binary Chiral Nanoparticles Exhibit Amplified Optical Activity and Enhanced Refractive Index Sensitivity.

Metallic chiral nanoparticles (CNPs) with a nominal helical pitch (P) of sub-10 nm contain inherent chirality and are promisingly applied to diverse prominent enantiomer-related applications. However, the sub-wavelength P physically results in weak optical activity (OA) to prohibit the development of these applications. Herein, a facile method to amplify the CNPs' OA by alloying the host CNPs with metals through a three-step layer-by-layer glancing angle deposition (GLAD) method is devised. Promoted by the GLAD-induced heating effect, the solute metallic atoms diffuse into the host CNPs to create binary alloy CNPs. Chiral alloying not only induces the plasmonic OA of the diffused solute and the created alloys but also amplifies that of the host CNPs, generally occurring for alloying Ag CNPs with diverse metals (including Cu, Au, Al, and Fe) and alloying Cu CNPs with Ag. Furthermore, the chiral alloying leads to an enhancement of refractive index sensitivity of the CNPs. The alloy CNPs with amplified plasmonic OA pave the way for potentially developing important chirality-related applications in the fields of heterogeneous asymmetric catalysis, enantiodifferentiation, enantioseparation, biosensing, and bioimaging.

Chirality Transfer in Galvanic Replacement Reactions.

Demand for the transfer of chirality from a pre-engineered nanoparticle to any other metal is of fundamental importance for developing a wide range of chirality-related applications. Herein, we show that binary alloy chiral nanoparticles (CNPs) with an engineerable composition can be formed from metallic CNPs with intrinsic structural chirality serving as sacrificial templates (STs), via a galvanic replacement reaction (GRR). This GRR-mediated chirality transfer is a general phenomenon and results in the formation of Cu-Ag CNPs with solid morphology and mesoporous CNPs made of Ag-Au, Ag-Pt, and Ag-Pd. Our study imposes a new component, i.e., structural chirality, on the GRR. The insights from our study improve our fundamental understanding of the GRR principle and devise a versatile method to generate mesoporous alloy CNPs for developing prominent chirality-related applications in asymmetric catalysis, enantiodifferentiation, enantioseparation, biodetection, and bioimaging.

Chiral Cux Coy S Nanoparticles under Magnetic Field and NIR Light to Eliminate Senescent Cells.

In the present study, chiral Cux Coy S nanoparticles (NPs) were developed to selectively induce apoptosis of senescent cells using both an alternating magnetic field (AMF) and near infrared (NIR) photon illumination. The chiral effects on living cells were investigated, and d-Cux Coy S NPs showed about 2.5 times higher of internalized ability than l-NPs. By modifying beta 2 macroglobulin (MG), senescent cells were effectively eliminated by d-Cux Coy S NPs without damaging the activities of normal cells under AMF and photon illumination. Compared to the individual application of NIR illumination and AMF, their synergistic effect induced the production of caspase-3 with a much shorter treatment time and higher efficiency due to the more serious photon-induced cellular redox and mechanical damage of cellular skeleton. Moreover, the developed strategy was successfully used to remove senescent cells in vivo. This study developed a controllable way of regulating cell activities using chiral NPs, which will provide a valuable way for treating diseases and promoting health.

Isothermal titration calorimetry for chiral chemistry.

One of the most powerful techniques that are currently available to measure thermodynamic parameters such as enthalpy (ΔH), Gibbs free energy (ΔG), entropy changes (ΔS), and binding affinity in chemical reactions is isothermal titration calorimetry (ITC). Recent advances in instrumentation have facilitated the development of ITC as a very essential analytical tool in biology and chemistry. In this article, we will focus on a review of the literature on the application of ITC for the study of chiral systems and chiral interactions. We present studies in which the ITC technique is used to study chiral interactions, for instance in chiral solutions, chiral organometallic complexes, guest-host chiral binding interactions, and biological macromolecules. Finally, we put strong emphasis on the most recent application of ITC for the study of chirality in nanosystems and at the nanoscale.

Enantioseparation of Mandelic Acid Enantiomers With Magnetic Nano-Sorbent Modified by a Chiral Selector.

In this study, R(+)-α-methylbenzylamine-modified magnetic chiral sorbent was synthesized and assessed as a new enantioselective solid phase sorbent for separation of mandelic acid enantiomers from aqueous solutions. The chemical structures and magnetic properties of the new sorbent were characterized by vibrating sample magnetometry, transmission electron microscopy, Fourier transform infrared spectroscopy, and dynamic light scattering. The effects of different variables such as the initial concentration of racemic mandelic acid, dosage of sorbent, and contact time upon sorption characteristics of mandelic acid enantiomers on magnetic chiral sorbent were investigated. The sorption of mandelic acid enantiomers followed a pseudo-second-order reaction and equilibrium experiments were well fitted to a Langmuir isotherm model. The maximum adsorption capacity of racemic mandelic acid on to the magnetic chiral sorbent was found to be 405 mg g(-1). The magnetic chiral sorbent has a greater affinity for (S)-(+)-mandelic acid compared to (R)-(-)-mandelic acid. The optimum resolution was achieved with 10 mL 30 mM of racemic mandelic acid and 110 mg of magnetic chiral sorbent. The best percent enantiomeric excess values (up to 64%) were obtained by use of a chiralpak AD-H column.

Tuning the Geometry and Optical Chirality of Pentatwinned Au Nanoparticles with 5-Fold Rotational Symmetry.

Chirality transfer from chiral molecules to chiral nanomaterials represents an important topic for exploring the origin of chirality in many natural and artificial systems. Moreover, developing a promising class of chiral nanomaterials holds great significance for various applications, including sensing, photonics, catalysis, and biomedicine. Here we demonstrate the geometric control and tunable optical chirality of chiral pentatwinned Au nanoparticles with 5-fold rotational symmetry using the seed-mediated chiral growth method. A distinctive growth pathway and optical chirality are observed using pentatwinned decahedra as seeds, in comparison with the single-crystal Au seeds. By employing different peptides as chiral inducers, pentatwinned Au nanoparticles with two distinct geometric chirality (pentagonal nanostars and pentagonal prisms) are obtained. The intriguing formation and evolution of geometric chirality with the twinned structure are analyzed from a crystallographic perspective upon maneuvering the interplay of chiral molecules, surfactants, and reducing agents. Moreover, the interesting effects of the molecular structure of peptides on tuning the geometric chirality of pentatwinned Au nanoparticles are also explored. Finally, we theoretically and experimentally investigate the far-field and near-field optical properties of chiral pentatwinned Au nanoparticles through numerical simulations and single-particle chiroptical measurements. The ability to tune the geometric chirality in a controlled manner represents an important step toward the development of chiral nanomaterials with increasing architectural complexity for chiroptical applications.

Enantioselective Antiviral Activities of Chiral Zinc Oxide Nanoparticles.

Chiral nanoparticles (C-NPs) play a crucial role in biomedical applications, especially in their biological effects on cytotoxicity and metabolism. However, there are rare reports about the antivirus property of C-NPs and their working mechanism. Here, three different types of chiral ZnO NPs (l-ZnO, d-ZnO, and dl-ZnO) were prepared as enantioselective antivirals. Biocompatibility test results showed that the three different chiral ZnO NPs varied significantly in cytotoxicity. Evaluation of their effects against porcine reproductive and respiratory syndrome virus (PRRSV) indicated that compared with d-ZnO and dl-ZnO NPs, l-ZnO NPs exhibited stronger anti-PRRSV activity due to their higher cognate cell adhesion and uptake. Furthermore, the high concentration of l-ZnO NPs can obviously reduce cellular reactive oxygen species (ROS) in MARC-145 cells, thus effectively preventing PRRSV-induced oxidative damage. This study demonstrated the outstanding antiviral properties of l-ZnO NPs, which may facilitate the development and application of C-NPs in antiviral drugs and tissue engineering.

Tunable Reversal of Circular Dichroism in the Seed-Mediated Growth of Bichiral Plasmonic Nanoparticles.

Plasmonic nanoparticles with an intrinsic chiral structure have emerged as a promising chiral platform for applications in biosensing, medicine, catalysis, separation, and photonics. Quantitative understanding of the correlation between nanoparticle structure and optical chirality becomes increasingly important but still represents a significantly challenging task. Here we demonstrate that tunable signal reversal of circular dichroism in the seed-mediated chiral growth of plasmonic nanoparticles can be achieved through the hybridization of bichiral centers without inverting the geometric chirality. Both experimental and theoretical results demonstrated the opposite sign of circular dichroism of two different bichiral geometries. Chiral molecules were found to not only contribute to the chirality transfer from molecules to nanoparticles but also manipulate the structural evolution of nanoparticles that synergistically drive the formation of two different chiral centers. By deliberately adjusting the concentration of chiral molecules and other synthetic parameters, such as the reducing agent concentration, the capping surfactant concentration, and the amount of Au precursor, we have been able to fine-tune the circular dichroism reversal of bichiral Au nanoparticles. We further demonstrate that the structure of chiral molecules and the crystal structure of Au seeds play crucial roles in the formation of Au nanoparticles with bichiral centers. The insights gained from this work not only shed light on the underlying mechanisms dictating the intriguing geometric and chirality evolution of bichiral plasmonic nanoparticles but also provide an important knowledge framework that guides the rational design of bichiral plasmonic nanostructures toward chiroptical applications.