Enantioselective Interactions Research Articles

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

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

Enhancing Electrochemical Signal for Efficient Chiral Recognition by Encapsulating C60 Fullerene into Chiral Lanthanum-Based MOFs.

Chiral metal-organic frameworks (MOFs) have attracted much attention due to their highly tunable regular microporous structures. However, chiral electrochemical recognition based on chiral MOFs is often limited by poor charge separation and slow charge transfer kinetics. In this case, C60 can be encapsulated into the cavity of [La(BTB)]n by virtue of host-guest interactions through π-π stacking to synthesize the chiral composite C60@[La(BTB)]n and amplify electrochemically controlled enantioselective interactions with the target enantiomers. A large electrostatic potential difference is generated in chiral C60@[La(BTB)]n due to the host-guest interaction and the inhomogeneity of the charge distribution, leading to the generation of a strong built-in electric field and thus an overall enhancement of the conductivity of the chiral material. Their enantioselective detection of tryptophan enantiomers was demonstrated by electrochemical measurement. The results showed that chiral MOF materials can be used for enantiomeric recognition. It is worth noting that this new material derived from the concept of host-guest interaction to enhance charge separation opens up unprecedented possibilities for future enantioselective recognition and separation.

Supramolecular Chiral Binding Affinity-Achieved Efficient Synergistic Cancer Therapy.

Supramolecular chirality-mediated selective interaction among native assemblies is essential for precise disease diagnosis and treatment. Herein, to fully understand the supramolecular chiral binding affinity-achieved therapeutic efficiency, supramolecular chiral nanoparticles (WP5⊃D/L-Arg+DOX+ICG) with the chirality transfer from chiral arginine (D/L-Arg) to water-soluble pillar[5]arene (WP5) are developed through non-covalent interactions, in which an anticancer drug (DOX, doxorubicin hydrochloride) and a photothermal agent (ICG, indocyanine green) are successfully loaded. Interestingly, the WP5⊃D-Arg nanoparticles show 107 folds stronger binding capability toward phospholipid-composed liposomes compared with WP5⊃L-Arg. The enantioselective interaction further triggers the supramolecular chirality-specific drug accumulation in cancer cells. As a consequence, WP5⊃D-Arg+DOX+ICG exhibits extremely enhanced chemo-photothermal synergistic therapeutic efficacy (tumor inhibition rate of 99.4%) than that of WP5⊃L-Arg+DOX+ICG (tumor inhibition rate of 56.4%) under the same condition. This work reveals the breakthrough that supramolecular chiral assemblies can induce surprisingly large difference in cancer therapy, providing strong support for the significance of supramolecular chirality in bio-application.

Dependence on the crystallographic orientation of Au single crystal surfaces modified with homocysteine toward enantioselective redox reactions

Abstract Effects of enantioselective interactions on redox reactions of chiral molecules were studied using Au single crystal electrodes modified with amino acids. The redox peak current densities of R(+)- or S(−)-N, N-dimethyl-1-ferrocenylethylamine on Au(111) modified with L- or D-homocysteine (L-/D-Hcy) depended on the combination of these chiralities. Hcy/Au(100) showed no dependence on redox peak current densities. The difference in the molecular arrangement of Hcy between Au(111) and Au(100) greatly affects enantioselective redox reactions at the electrode interface.

Engineering copper plasmonic chirality via ligand-induced dissolution for enantioselective recognition of amino acids.

The formation of chiral nanosystems and their subsequent enantioselective interaction with chiral amino acids are vital steps in many biological processes. Due to their potential to mimic biological systems, the synthesis of chiral nanomaterials has garnered significant attention over the years. Despite the emergence of diverse nanomaterials showcasing strong chiral responses, the in-depth understanding of the mechanism of plasmonic chirality in copper nanoparticles and their subsequent application in various fields are least explored. Herein, we demonstrate a facile approach for the synthesis of chiral copper nanoparticles using cysteine as a chiral precursor and capping ligand. Ligand-mediated chiral induction, established through experimental findings and a theoretical model, is ascribed as the major contributor to the origin of plasmonic chirality. The enantioselective recognition of chiral copper nanoparticles towards histidine, an amino acid with vast biological functions, was meticulously investigated by leveraging the strong copper-histidine binding ability. Ligand-induced dissolution, a unique phenomenon in nanoparticle reactions, was identified as the underlying mechanism for the nanoparticle-to-complex conversion. Understanding the mechanism of chiral induction in copper nanoparticles coupled with their enantioselective recognition of biomolecules not only holds promise in biomedical research but also sheds light on their potential as catalysts for asymmetric synthesis.

Redox-Mediated Enantioselective Interactions in Chiral Metallopolymers Possessing Supramolecular Chirality

Synthetic chiral platforms can be a powerful platform for enantioselective interactions, especially when coupled with redox-mediated electrochemical processes. Redox metallopolymers represent a distinct class of versatile functional materials and have been extensively studied for a wide scope of applications such as membranes, self-assembly, hydrogels, and redox-mediated ion separation. However, many studies have focused on molecularly-selective binding and release of achiral molecules, with limited studies on chirality strategies for enantioselective interactions. Chiral organic anions comprise an important class of biologically-relevant molecules, and their separation and sensing have received intense attention. Here, we introduce new chiral redox-polymers with chiral ferrocene (Fc) building blocks, that can serve as an electro-responsive enantioselective platform for a variety of amino acids and pharmaceutical carboxylates, taking advantage of supramolecular chirality for enhancing electrochemical recognition. Two chiral redox-metallopolymers were designed and synthesized based on Ugi’s amine-inspired chiral monomers containing an amide (poly-1) or amine group (poly-2), and their enantioselective recognitions toward amino acids and pharmaceutical carboxylates were investigated by redox potential shifts using square wave voltammetry. The half potential shift of both poly-(S)-1 and poly-(S)-2 increased more with increasing D-tryptophan concentration than the other enantiomer, L-tryptophan, while the half potential of poly-(R)-1 and poly-(R)-2 shifted more with L-tryptophan than with D-tryptophan, proving the enantioselective interaction of both redox-metallopolymers. Nuclear Overhauser Effect spectroscopy (2D NOESY) and solid-state circular dichroism revealed the emergence of supramolecular chirality of the polymers resulting from the intramolecular interaction between the ferrocene and the alkyl group in the backbone, and the steric hindrance of the ferrocene within the polymer. The half-peak potential shift demonstrated the remarkable enhancement of enantioselective recognition with tryptophan (Trp) and naproxen, provided by the chiral polymers possessing the supramolecular chirality over the single-site, chiral building block itself. For instance, the two (S) polymers showed the potential shift difference 2.4-2.8 times higher than the corresponding monomers upon the binding of Trp enantiomers. The enantioselective potential shift of the chiral metallopolymer electrodes could determine enantiomeric excess (%ee) of Trp over the range of 0–100%ee. Investigation on solvent polarity and pH effect revealed that the enantioselective mechanism of the chiral redox polymers was attributed to the subtle balance between hydrogen bonding and π-π interaction. We also identified the importance of aromatic groups on the analytes for increasing enantioselectivity of the chiral redox polymers. This work highlights the potential of chiral redox-metallopolymers as platforms for electrochemically-modulated enantioselective processes toward a variety of amino acids and pharmaceutical carboxylates. Figure 1

Enantiosensitive growth dynamics of chiral molecules on ferromagnetic substrates and the origin of the CISS effect.

The recent demonstration of the existence of an intimate relationship between the chiral structure of some materials and the spin polarization of electrons transmitted through them, what has been called the chirality-induced spin selectivity (CISS) effect, is sparking interest in many related phenomena. One of the most notorious is the possibility of using magnetic materials to apply enantioselective interactions on chiral molecules and chemical reactions involving them. In this work, x-ray photoelectron spectroscopy has been used to characterize the adsorption and growth kinetics of enantiopure organic molecules on magnetic (Co) and non-magnetic (Cu) substrates. While on these latter, no significant enantiosensitive effects are found, on spin-polarized, in-plane magnetized Co surfaces, the two enantiomers have been found to deposit differently. The observed effects have been interpreted as the result of one of the enantiomers being adsorbed in a transient, weakly bound physisorbed-like state with higher mobility due to limited, spin-selective charge transfer between it and the substrate. The study of these phenomena can provide insight into the fundamental mechanisms responsible for the CISS effect.

The enantioselective enhancing effect and mechanistic insights of chiral enhancers in transdermal drug delivery

Overlook of chiral consideration in transdermal drug delivery increases administrated dose and risk of side effects, decreasing therapeutical effects. To improve the transdermal delivery efficiency of eutomer, this work focused on investigating the law and mechanism of enantioselective enhancing effects of chiral permeation enhancers on drug enantiomers. Chiral nonsteroidal anti-inflammatory drugs and terpene permeation enhancers were selected as model drug and enhancers. The results indicated that the L-isomer of permeation enhancers increased the skin absorption of S-enantiomer of drug and D-isomer improve the permeation of R-enantiomer, in which the enhancement effect (ER) of L-menthol on S-enantiomer (ER = 3.23) was higher than that on R-enantiomer (ER = 1.49). According to the pharmacokinetics results, L-menthol tended to enhance the permeation of S-enantiomer better than R-enantiomer (2.56 fold), and showed excellent in vitro/in vivo correlations. The mechanism study showed that L-isomer of permeation enhancers improved the permeation of S-enantiomer by increasing the retention, but the D-isomer by improving partition for better permeation. Enantioselective mechanism indicated that the weaker chiral H-bond interaction between drug-chiral enhancers was caused by the enantiomeric conformation. Additionally, stronger chiral enhancers-skin interaction between L-isomer and S-conformation of ceramide produced better enhancing effects. In conclusion, enantioselective interaction of chiral drug-chiral enhancers and chiral enhancers-chiral skin played a critical role in transdermal drug delivery, rational utilization of which contributed to improving the uptake of eutomer and inhibiting distomers to decrease a half of dose and side effects, increasing transdermal therapeutical efficiency.

Chiral Metallopolymers for Redox‐Mediated Enantioselective Interactions

AbstractSynthetic chiral platforms can be a powerful platform for enantioselective interactions, especially when coupled with redox‐mediated electrochemical processes. While metallopolymers are versatile platforms for molecularly selective binding, their application for chiral applications is limited. In particular, the recognition and separation of biologically relevant chiral molecules can be key for biomanufacturing and diagnostics. Here, the design of chiral redox‐polymers enables electrochemically‐controlled enantioselective interactions, and supramolecular chirality is leveraged for enhancing recognition towards target enantiomers. Chiral redox‐metallopolymers are synthesized based on Ugi's amine‐inspired chiral monomers, and their enantioselective recognition toward ionic enantiomers such as tryptophan and naproxen is demonstrated, with higher enanhcement provided by the chiral redox‐polymer over the single‐site, chiral building bloack itelf. 2D nuclear magnetic resonance spectroscopy and solid‐state circular dichroism support the emergence of supramolecular chirality resulting from the intramolecular interaction between the ferrocene and the alkyl group in the backbone. The half potential shift of the redox‐polymers behaves linearly from 0% to 100%ee l‐tryptophan to enable enantiomer quantification. Investigation on solvent polarity and pH effect reveal that the enantioselective mechanism is attributed to the subtle balance between hydrogen bonding and π–π interaction. This study highlights the potential of chiral redox‐metallopolymers as platforms for electrochemically‐modulated enantioselective interactions towards a range of amino acids and pharmaceutical carboxylates.

Chiral Detection of Glucose: An Amino Acid-Assisted Surface-Enhanced Raman Scattering Strategy Showing Opposite Enantiomeric Effects on SERS Signals

It is of considerable concern to establish chiral detection methods for revealing enantioselective interactions among chiral molecules. Surface-enhanced Raman scattering (SERS) spectroscopy is sensitive to molecular interaction due to bond variations. However, its application in chiral detection is underexplored. Inspired by the chiral selectivity toward glucose and amino acids in life, we herein propose a SERS strategy based on molecular interactions for the discrimination of d- and l-glucose (Glu) using chiral phenylalanine (Phe) decorated on gold nanoparticles as a chirality selector and Raman reporter. Interestingly, the SERS signal of l-Phe is enhanced by d-Glu but suppressed by l-Glu. In contrast, the SERS signal of d-Phe is increased by l-Glu but decreased by d-Glu. According to the above-observed intensity change (ΔI) of the SERS signal of Phe induced by Glu, it is easy to determine the chiral configurations (judged by the positive or negative sign of ΔI), enantiomeric excess (ee) values, and concentrations (estimated by the magnitude of ΔI) of Glu. Taking advantage of the high SERS enhancement and opposite enantiomeric effects on SERS signals, the proposed strategy enables enantiomeric discrimination at a low Glu concentration (10-6 mol/L) and is further exerted for the noninvasive detection of d-/l-Glu in saliva samples. In contrast, the common chiroptical analysis tool of circular dichroism (CD) spectroscopy failed to directly detect Glu enantiomers.

Recognition of 3D Chiral Microenvironments for Myoblast Differentiation.

Cell chirality plays a critical role in the linkage between molecular chirality and the asymmetrical biological functions of body organs. However, enantioselective interactions between cell chirality and the extracellular environment are not yet fully understood. In this study, we investigated the effects of structurally chiral extracellular microenvironments on cellular alignments and differentiations. Twisted wrinkle-shaped chiral micropatterns were prepared using biaxial and asymmetric buckling methods, wherein structural handedness was determined from the orientation of the tilt angle between the first and second microwrinkles. Myoblasts were separately cultured on two enantiomeric chiral micropatterns in a mirror-reflected shape. Cells cultured on the left-handed chiral micropatterns preferred alignments along the direction of the second microwrinkle, with a relatively deeper valley than that of the first microwrinkle. The aligned cells on the left-handed pattern showed higher differentiation rates, as assessed by fusion indices and marker protein expression levels, than those cultured on right-handed chiral micropatterns. These results suggest that myoblasts exhibit enantioselective recognition of structurally chiral microenvironments, which can promote cellular alignments and differentiation.

Adenine oligomer directed synthesis of chiral gold nanoparticles

Precise control of morphology and optical response of 3-dimensional chiral nanoparticles remain as a significant challenge. This work demonstrates chiral gold nanoparticle synthesis using single-stranded oligonucleotide as a chiral shape modifier. The homo-oligonucleotide composed of Adenine nucleobase specifically show a distinct chirality development with a dissymmetric factor up to g ~ 0.04 at visible wavelength, whereas other nucleobases show no development of chirality. The synthesized nanoparticle shows a counter-clockwise rotation of generated chiral arms with approximately 200 nm edge length. The molecular dynamics and density functional theory simulations reveal that Adenine shows the highest enantioselective interaction with Au(321)R/S facet in terms of binding orientation and affinity. This is attributed to the formation of sequence-specific intra-strand hydrogen bonding between nucleobases. We also found that different sequence programming of Adenine-and Cytosine-based oligomers result in chiral gold nanoparticles’ morphological and optical change. These results extend our understanding of the biomolecule-directed synthesis of chiral gold nanoparticles to sequence programmable deoxyribonucleic acid and provides a foundation for programmable synthesis of chiral gold nanoparticles.

Interactions of diclazuril enantiomers with serum albumins: Multi-spectroscopic and molecular docking approaches.

In this work, multi-spectroscopic and molecular docking methods have been conducted in the investigation of enantioselective interactions between diclazuril enantiomers and human/bovine serum albumins (HSA/BSA). The binding constants between serum albumins (SAs) and diclazuril enantiomers revealed that SAs exhibited stronger binding affinity for (R)-diclazuril than (S)-enantiomer. In addition, the fluorescence quenching of SAs induced by diclazuril enantiomers was ascribed to static quenching mechanism, in which hydrogen bonds and Van der Waals forces were the main interactions. According to the thermodynamic study, binding of diclazuril enantiomers and SAs was an exothermic process driven by enthalpy change. Then, circular dichroism spectroscopy of SAs with diclazuril enantiomers revealed that the SAs conformation had changed in the presence of diclazuril. Moreover, molecular docking technology was applied in exploration of interactions between SAs and diclazuril enantiomers. The docking energy between SAs and (R)-diclazuril was larger than (S)-diclazuril, which indicated that the affinity of SAs with (R)-diclazuril was stronger than (S)-enantiomer. This work may provide valuable information for explaining differences in pharmacokinetics and residue elimination of diclazuril enantiomers in living organisms.

Cooperative interaction between organic and inorganic moieties in hybrid silica nanohelices for enantioselective interaction.

Hybrid nanometric helical structures formed by the molecular assemblies of dicationic gemini surfactants with tartrate counterions covered with helical silica walls interact differently with matching or mismatching enantiomers of the tartrate. The difference of the interaction is based on the cooperativity between the chiral crystalline gemini surfactant molecular organization/conformation and the rigid chiral nanospace formed by the helical silica wall.

Enantioselective Interaction between Cells and Chiral Hydroxyapatite Films

Enantioselective Interaction between Cells and Chiral Hydroxyapatite Films

Plasmonic Nanosensors with Extraordinary Sensitivity to Molecularly Enantioselective Recognition at Nanoscale Interfaces.

Molecular chirality recognition plays a pivotal role in chiral generation and transfer in living systems and makes important contribution to the development of diverse applications spanning from chiral separation to soft nanorobots. To detect chirality recognition, most of the molecular sensors described to date are based on the design and preparation of the host-guest complexation with chromophore or fluorophore at the reporter unit. Nevertheless, the involved tedious procedures and complicated chemical syntheses hamper their practical applications. Here, we report the plasmonically chiroptical detection of molecular chirality recognition without the need for a chromophore or fluorophore unit. This facile methodology is based on plasmonic nanotransducers that can convert molecular chirality recognitions occurring at nanoscale interfaces into asymmetrically amplified plasmonic circular dichroism readouts, enabling enantiospecific recognition and quantitative determination of the enantiomeric excess of small amino acids. Importantly, such a plasmon-based chirality sensing shows 102-103 amplification in the plasmonic circular dichroism signals from the detections of racemate and near-racemate of molecular analysts, demonstrating an extraordinary sensitivity to the host-guest enantioselective interactions. Furthermore, with advantages of easy-processing, cost-effective, and specific to interfacial molecular chirality, our chiroptical sensing scheme could hold considerable promise toward applications of enantioselective high-throughput screening in biology, stereochemistry, and pharmaceutics.

Engineering of inorganic nanostructures with hierarchy of chiral geometries at multiple scales

Engineering of inorganic nanostructures with hierarchy of chiral geometries at multiple scales

Construction of a novel highly electroactive nano-composite film modified with cellulose gum for the electrochemical recognition of tryptophan isomers

Ferrocene (Fc) was introduced into the layers of graphene oxide (GO) to form rGO-Fc with large surface area, high loading and high electroactivity. A chiral carbon nanocomposite rGO-Fc-CMC was synthesized via the adsorptional interaction between rGO-Fc and sodium carboxymethyl cellulose (CMC), and the successful synthesis of the chiral carbon nanocomposite (rGO-Fc-CMC) was showed by a series of characterization methods including scanning electron microscopy (SEM), Fourier transform infrared (FT-IR), X-ray photoelectron spectroscopy (XPS). The enantioselective interaction between chiral carbon nanocomposite (rGO-Fc-CMC) and tryptophan (Trp) enantiomers was detected by differential pulse voltammetry (DPV). The results demonstrated that the rGO-Fc-CMC/GCE showed a higher enantioselective capability for Trp than CMC/GCE, which can successfully break the limitation of a poor conductivity on CMC via the expansion of electrochemical signal. Therefore, designing an excellent-performance chiral carbon nanocomposite is of great significance in the construction of electrochemical sensors for chiral recognition.

Evidence for new enantiospecific interaction force in chiral biomolecules

Evidence for new enantiospecific interaction force in chiral biomolecules

Self-Templated, Enantioselective Assembly of an Amyloid-like Dipeptide into Multifunctional Hierarchical Helical Arrays.

Chiral self-assembly of peptides has attracted great interest owing to their promising applications in biomedicine, chemistry, and materials science. However, compared with the rich knowledge about their chiral self-assembly at the molecular or nanoscale, the formation of long-range-ordered hierarchical helical arrays (HHAs) from simple peptides remains a formidable challenge. Herein, we report the self-templated assembly of an amyloid-like dipeptide into long-range-ordered HHAs by their spontaneous fibrillization and hierarchical helical assembly within a confined film. The chiral interactions between the peptide and diamines result in geometry frustration and the phase transition of self-assembling peptide films from achiral spherulite structures into chiral HHAs. By changing the chirality and enantioselective interactions, we can control the phase behavior, handedness, and chiroptics of the self-assembled HHAs precisely. Moreover, the redox activity of the HHAs allows the in situ decoration of nanoparticles with high catalytic activity. These results provide insights into the chiral self-assembly of peptides and the fabrication of highly ordered materials with complex architectures and promising applications in chiroptics and catalysis.