Chiral Cavity Research Articles

Self-Assembly and Chiral Recognition of Chiral Cationic Gemini Surfactants.

Chiral cationic gemini surfactants 1,4-bis(dodecyl- N, N-dimethylammonium bromide)-2,3-butanediol (12-4(OH)2-12) including racemate, mesomer, and two enantiomers were synthesized and their self-assembly in aqueous solution has been comparatively investigated by tensiometry, conductometry, 1H NMR, small-angle neutron scattering, cryogenic transmission electron microscopy, and cryogenic scanning electron microscopy. The chirality at spacer induces different self-assembly behaviors due to the hydrogen-bonding interaction between the hydroxyl groups at the chiral centers. The stereochemistry of the spacer has little effect on the release of the counterions from the surfactant headgroups and on the molecular packing at the air-water interface. The critical micelle concentration (CMC) decreases in the order of racemate > enantiomer > mesomer. Above the CMC, the aggregates of enantiomers transit from small spherical micelles to rodlike and wormlike micelles with increasing concentration, whereas the mesomer and racemate aggregates transform from spherical micelles to rodlike micelles and platelet-like aggregates. The differences may be because the mesomer and racemate molecules mainly form intermolecular hydrogen bonds between the -OH groups, but the enantiomer molecules dominantly form intramolecular hydrogen bonds. Furthermore, it was found that the chiral micelles formed by the enantiomers exhibit enantioselection ability for bilirubin (BR) enantiomers. The recognition capability can be adjusted by the micellar structure, i.e., the rodlike micelles are better than either small spherical micelles or wormlike micelles, which might possess different chiral cavities, controlling BR shape and location. These results demonstrate that the aggregates of chiral gemini surfactants can be used to mimic the chiral recognition in biological membrane.

Tunable normal phase enantioselectivity of amino acid esters via mobile phase composition

The ability to tune chiral selectivity through mobile phase modifiers is a powerful tool in chiral separations. Beyond improving efficiency and/or resolution, some mobile phase systems can even invert elution order, a highly desirable result for trace analyses or preparative scale isolations. Previous work has demonstrated that acidic modifiers, such as ethanesulfonic acid (ESA), can greatly impact separations of enantiomers. However, prior studies were primarily performed on coated chiral stationary phases (CSPs), which limited the selection of the bulk mobile phase component.In this work, the effect of ESA modifier was studied for the enantioseparation of six pairs of amino acid esters on a CHIRALPAK® IA column, an immobilized amylose-based CSP, with different combinations of standard solvents (hexane and ethanol) as well as “non-standard” solvents, such as methyl t-butyl ether, ethyl acetate, tetrahydrofuran, acetone, or 1,4-dioxane. ESA generally improved selectivity, and multiple instances of elution order reversal were observed. A Van Deemter plot study reveals that ESA exerts its effect by pulling the enantiomer deeper into the chiral cavity of the chiral polymer to increase the interactions between the analytes and the stationary phase, which is the main reason for the increased enantioselectivity.

The True Catalyst Revealed: The Intervention of Chiral Ca and Mg Phosphates in Brønsted Acid Promoted Asymmetric Mannich Reactions

The acetylacetone-benzaldimine Mannich reaction catalyzed by Mg(II) and Ca(II) salts of chiral phosphoric acids (CPA) has been investigated computationally by QM/MM methods. Enantioselectivity in this reaction is both larger than and in the opposite sense to that observed for the same reaction catalyzed by the protic CPA catalyst alone. We present a mechanistic model from which the characteristic differences between these metal and metal-free catalysts, which can coexist in the same reaction mixture, can be understood. Alkaline earth salts with chiral phosphate counterions are found to be more catalytically active than the protic form, and the Ca(II) and Mg(II) CPA salts react via different mechanisms, with a higher coordination number favored by calcium over magnesium. In the well-ordered chiral cavities around these metal centers, asymmetric induction arises from the steric interaction with the imine protecting group in the unfavorable pathway, with both substrates adopting well-defined conformations. These mechanistic models have allowed us to rationalize the stereochemical outcome across a range of bimolecular reactions promoted by divalent metal phosphates formed with different CPAs.

Triple Helicene Cage: Three-Dimensional π-Conjugated Chiral Cage with Six [5]Helicene Units.

A three‐dimensional π‐conjugated chiral cage with six [5]helicene units (a triple helicene cage) was synthesized for the first time. Taking advantage of the Yamamoto coupling reaction, the triflate‐substituted triple [5]helicene, a strained and preorganized precursor, was dimerized to afford the target compound. Single‐crystal X‐ray diffraction analysis revealed the unique structural features of the triple helicene cage: a cage‐shaped rigid structure with outer helical grooves and an inner chiral cavity. All‐P and all‐M enantiomers were separated successfully by HPLC over a chiral column and their chiroptical properties were characterized by circular dichroism spectra.

Vesicles Constructed with Chiral Amphiphilic Oxacalix[2]arene[2]triazine Derivatives for Enantioselective Recognition of Organic Anions.

Chiral amphiphilic oxacalix[2]arene[2]triazine derivatives 1-3 bearing l-prolinol moieties were synthesized. The self-assembly behavior of the chiral macrocyclic amphiphiles was investigated. SEM, TEM, and DLS measurements demonstrated that 1 formed stable vesicles (size of ∼90 nm), whereas 2 and 3 formed micelles. As monitored by DLS, vesicles composed of 1 showed selective response to the chiral anions (2S, 3S)-2,3-dihydroxysuccinate (d-tartrate), S-mandelate and S-(+)-camphorsulfonate over their enantiomers. DFT calculations revealed that the enantioselectivity arises from cooperative anion-π interactions and hydrogen bonding between the chiral electron-deficient cavity and the organic anions.

Thermodynamic enantioseparation behavior of phenylthiohydantoin-amino acid derivatives in supercritical fluid chromatography on polysaccharide chiral stationary phases.

Thirteen pairs of enantiomers belonging to the same structural family (phenylthiohydantoin-amino acids) were analyzed on two polysaccharide chiral stationary phases, namely, tris-(3,5-dimethylphenylcarbamate) of amylose (Chiralpak AD-H) or cellulose (Chiralcel OD-H) in supercritical fluid chromatography with a carbon dioxide/methanol mobile phase (90:10 v/v). Five different temperatures (5, 10, 20, 30, 40°C) were applied to evaluate the thermodynamic behavior of these enantioseparations. On the cellulose stationary phase, the retention, and separation trends were most similar among the set of probe analytes, suggesting that the chiral cavities in this stationary phase have little diversity, or that all analytes accessed the same cavities. Conversely, the retention and separation trends on the amylose phase were much more diverse, and could be related to structural differences among the set of probe analytes (carbon chain length in the amino acid residue, secondary amine in proline, existence of covalent rings, or formation of pseudo-rings via intramolecular hydrogen bonds). The large variability of behaviors on the amylose phase suggests that the chiral-binding sites in this chiral stationary phase have more variety than on the cellulose phase, and that the analytes did access different cavities.

Chiral metals as electrodes

Summary Chirality is one of the most fascinating issues in chemical researches. In this review, the development of chiral metals is summarized from the past to the present. Several very recent concepts for generating chiral metals, such as the design of chiral imprinted cavities at mesoporous metal surfaces, are also presented. The application of chiral metals as electrodes in the enantioselective recognition and asymmetric synthesis of chiral compounds reveals that these designer surfaces open up potential perspectives for the development of new materials for chiral technologies.

Post-Cross-Linked Molecular Imprinting with Functional Polymers as a Universal Building Block for Artificial Polymeric Receptors

A post-cross-linked molecular imprinting (PC-MI) technique utilizing a functional polymer (FP) with interacting and post-cross-linking groups was developed to create molecularly imprinted polymeric (MIP) receptors. Molecular recognition cavities were formed in the cross-linked polymer matrix by a posteriori cross-linking of the FP with template molecules using photoirradiation. These cavities could be easily tuned to recognize the target molecules by changing the template using a common FP as a universal building block. Thus, precise chiral recognition cavities were successfully created using PC-MI and optimizing the molar ratio of the functional groups between the FP and the target molecules, which suppressed the nonspecific binding of the off-target molecules. Furthermore, the morphology of the MIPs could be changed from bulk to particles. This study provides a facile and efficient synthetic route for MIPs with tailor-made properties. Thus, PC-MI can be utilized to create molecular recognition elements ...

Enantioselective Anion Recognition by Chiral Halogen-Bonding [2]Rotaxanes.

The application of chiral interlocked host molecules for discrimination of guest enantiomers has been largely overlooked, which is surprising given their unique three-dimensional binding cavities capable of guest encapsulation. Herein, we combined the stringent linear geometric interaction constraints of halogen bonding (XB), the noncovalent interaction between an electrophilic halogen atom and a Lewis base, with highly preorganized and conformationally restricted chiral cavities of [2]rotaxanes to achieve enantioselective anion recognition. Representing the first detailed investigation of the use of chiral XB rotaxanes for this purpose, extensive 1H NMR binding studies and molecular dynamics (MD) simulation experiments revealed that the chiral rotaxane cavity significantly enhances enantiodiscrimination compared to the non-interlocked free axle and macrocycle components. Furthermore, by examining the enantioselectivities of a family of structurally similar XB [2]rotaxanes containing different combinations of chiral and achiral macrocycle and axle components, the dominant influence of the chiral macrocycle in our rotaxane design for determining the effectiveness of chiral discrimination is demonstrated. MD simulations reveal the crucial geometric roles played by the XB interactions in orientating the bound enantiomeric anion guests for chiral selectivity, as well as the critical importance of the anions' hydration shells in governing binding affinity and enantiodiscrimination.

Chiral Macrocyclic Organocatalysts for Kinetic Resolution of Disubstituted Epoxides with Carbon Dioxide.

Among chiral macrocycles 1 synthesized, 1m with the 3,5-bis(trifluoromethyl)phenylethynyl group was the best organocatalyst for the enantioselective synthesis of cyclic carbonates from disubstituted or monosubstituted epoxides and CO2. The X-ray crystal structure of 1m revealed a well-defined chiral cavity with multiple hydrogen-bonding sites that is suitable for the enantioselective activation of epoxides. A catalytic cycle proposed was supported by DFT calculations.

Chiral Discrimination of Diamines by a Binaphthalene-Bridged Porphyrin Dimer.

A pair of 1,1'-binaphthalene-bridged bisporphyrins, (R)- and (S)-H1, were designed to examine their chiral discrimination abilities toward a range of model diamines by using UV-vis absorption, CD, and 1H NMR spectroscopy with the assistance of DFT molecular modeling. The spectroscopic titrations revealed that (R)-/(S)-H1 could encapsulate (R)-/(S)-DACH and (R)-/(S)-PPDA in the chiral bisporphyrin cavities, leading to the selective formation of sandwich-type 1:1 complexes via dual Zn-N coordination interactions. In particular, the chiral recognition energy (ΔΔG°) toward (R)-/(S)-DACH was evaluated to be -4.02 kJ mol-1. The binding processes afforded sensitive CD spectral changes in response to the stereostructure of chiral diamines. Remarkable enantiodiscrimination effects were also detected in the NMR titrations of (R)-/(S)-H1, in which the nonequivalent chemical shift (ΔΔδ) can reach up to 0.57 ppm for (R)-/(S)-DACH. However, due to the large steric effect, another chiral diamine ((R)-/(S)-DPEA) could not be sandwiched in the chiral bisporphyrin cavity; therefore, (R)-/(S)-DPEA could hardly be discriminated by (R)-/(S)-H1. The present results demonstrate a chiral bisporphyrin host with integrated CD and NMR chiral sensing functions and also highlight the binding-mode-dependent character of its enantiodiscrimination performance for different chiral guests.

Induction of axial chirality in divanillin by interaction with bovine serum albumin.

Vanillin is a plant secondary metabolite and has numerous beneficial health applications. Divanillin is the homodimer of vanillin and used as a taste enhancer compound and also a promissory anticancer drug. Here, divanillin was synthesized and studied in the context of its interaction with bovine serum albumin (BSA). We found that divanillin acquires axial chirality when complexed with BSA. This chiroptical property was demonstrated by a strong induced circular dichroism (ICD) signal. In agreement with this finding, the association constant between BSA and divanillin (3.3 x 105 mol-1L) was higher compared to its precursor vanillin (7.3 x 104 mol-1L). The ICD signal was used for evaluation of the association constant, demonstration of the reversibility of the interaction and determination of the binding site, revealing that divanillin has preference for Sudlow’s site I in BSA. This property was confirmed by displacement of the fluorescent markers warfarin (site I) and dansyl-L-proline (site II). Molecular docking simulation confirmed the higher affinity of divanillin to site I. The highest scored conformation obtained by docking (dihedral angle 242°) was used for calculation of the circular dichroism spectrum of divanillin using Time-Dependent Density Functional Theory (TDDFT). The theoretical spectrum showed good similarity with the experimental ICD. In summary, we have demonstrated that by interacting with the chiral cavities in BSA, divanillin became a atropos biphenyl, i.e., the free rotation around the single bound that links the aromatic rings was impeded. This phenomenon can be explained considering the interactions of divanillin with amino acid residues in the binding site of the protein. This chiroptical property can be very useful for studying the effects of divanillin in biological systems. Considering the potential pharmacological application of divanillin, these findings will be helpful for researchers interested in the pharmacological properties of this compound.

Theoretical study on the mechanism and selectivity of asymmetric cycloaddition reactions of 3-vinylindole catalyzed by chiral N,N'-dioxide-Ni(II) complex

The mechanism and selectivity of the asymmetric cycloaddition reactions of 3-vinylindole towards methyleneindolinone (Diels–Alder reaction) or ketimine (aza-Diels–Alder reaction) were investigated theoretically by DFT and ONIOM methods. The non-catalytic DA reaction occurred in a two-stage one-step mechanism with the energy barriers of 17.0–29.6kcalmol−1. Reactivity index analysis indicated that the cycloaddition tended to occur by the most nucleophilic terminal C4 center in 3-vinylindole and the most electrophilic Cβ center in methyleneindolinone with lower activation energies, which accounted for the regioseletivity observed in experiment. For non-catalytic reactions, the slightly exo-preference stemmed from the stabilizing π-π stacking of two indole rings in substrates. In the presence of chiral N,N'-dioxide-Ni(II) complex, the bulky ortho-iPr group in aniline of ligand provided sufficient steric shielding around dienophile from the si-face attack in Diels–Alder reaction or re-face attack in aza-Diels–Alder reaction by diene, resulting in predominant products with excellent enantioselectivity (the favorable re-face attack in Diels–Alder reaction or si-face attack in aza-Diels–Alder reaction). A “pocket-like” chiral cavity constructed by chiral catalyst enhanced exo-diastereofacial selectivity significantly by maximizing the overlap of the two indole rings of substrates to avoid unfavorable steric repulsion between indole ring of 3-vinylindole and chiral ligand. Compared with catalytic aza-Diels–Alder reaction of 3-vinylindole and ketimine, the improved catalytic activity of chiral N,N'-dioxide-Ni(II) catalyst in Diels–Alder reaction of 3-vinylindole with methyleneindolinone contributed to the high turnover frequency (TOF=1.05×106s−1). These results were in good agreement with experimental observations.

Enantiomerically pure tetraphenylene-based homochiral macrocyclic tetramer and its recognition property towards C76 fullerene

The synthesis and characterization of novel homochiral oligomacrocycle species composed of enantiomerically-pure tetraphenylene were described. Structural studies showed that the macrocyclic molecule possessed a helical chiral cavity, which exhibited unique and efficient recognition affinity towards fullerene C76 in toluene, as demonstrated by UV–vis titration experiments. The binding results were also interpreted through semi-empirical calculations.

Development of Supramolecular Saccharide Sensors Based on Cyclodextrin Complexes and Self-assembling Systems.

Cyclodextrins (CDs) are water-soluble host compounds having nano-size hydrophobic cavities that enable them to incorporate organic molecules in water. Optically inert CDs can be efficiently combined with various types of chromoionophores and fluoroionophores. In this study, using diverse combinations of phenylboronic acid fluorescent sensors and azoprobes with CDs, the unique saccharide recognition functions of CD, chemically modified CD, and CD gel complexes based on their synergistic function are clarified, thereby confirming their use as supramolecular saccharide sensors. To realize novel supramolecular chirality, the twisted structure of two ditopic azoprobes inside the γ-CD chiral cavity is controlled by multi-point recognition of guest ions in water. As different types of supramolecular saccharide sensors, phenylboronic acid-based self-assembling systems are also reviewed.

Fiber ring resonator with a nanofiber section for chiral cavity quantum electrodynamics and multimode strong coupling.

We experimentally realize an optical fiber ring resonator that includes a tapered section with a subwavelength-diameter waist. In this section, the guided light exhibits a significant evanescent field which allows for efficient interfacing with optical emitters. A commercial tunable fiber beam splitter provides simple and robust coupling to the resonator. Key parameters of the resonator such as the out-coupling rate, free spectral range, and birefringence can be adjusted. Thanks to the low taper- and coupling-losses, the resonator exhibits an unloaded finesse of F=75±1, sufficient for reaching the regime of strong coupling for emitters placed in the evanescent field. The system is ideally suited for trapping ensembles of laser-cooled atoms along the nanofiber section. Based on measured parameters, we estimate that the system can serve as a platform for optical multimode strong coupling experiments. Finally, we discuss the possibilities of using the resonator for applications based on chiral quantum optics.

Asymmetric synthesis using chiral-encoded metal.

The synthesis of chiral compounds is of crucial importance in many areas of society and science, including medicine, biology, chemistry, biotechnology and agriculture. Thus, there is a fundamental interest in developing new approaches for the selective production of enantiomers. Here we report the use of mesoporous metal structures with encoded geometric chiral information for inducing asymmetry in the electrochemical synthesis of mandelic acid as a model molecule. The chiral-encoded mesoporous metal, obtained by the electrochemical reduction of platinum salts in the presence of a liquid crystal phase and the chiral template molecule, perfectly retains the chiral information after removal of the template. Starting from a prochiral compound we demonstrate enantiomeric excess of the (R)-enantiomer when using (R)-imprinted electrodes and vice versa for the (S)-imprinted ones. Moreover, changing the amount of chiral cavities in the material allows tuning the enantioselectivity.

Controlled Self-Assembly inside C-Shaped Polyaromatic Strips

Chirality-assisted synthesis (CAS) embodies a powerful strategy for the creation of chiral molecules with well-defined shapes and large cavities. In this communication, we show that C-shaped molecular receptors created with this approach bind to stacks of amphipathic perylenediimide (PDI) dyes. Evidence from 1 H NMR titrations, DOSY-NMR studies, and all-atom molecular dynamics simulations indicates that – in the preferred supramolecular binding mode – such polyaromatic strips specifically recognize stacked PDI dimers in solution. These results represent a key step toward the controlled self-assembly of dye molecules inside chiral cavities of shape-persistent, polyaromatic strips.

Optimized Spiral Metal-Gallium-Nitride Nanowire Cavity for Ultra-High Circular Dichroism Ultraviolet Lasing at Room Temperature.

Circularly polarized laser sources with small footprints and high efficiencies can possess advanced functionalities in optical communication and biophotonic integrated systems. However, the conventional lasers with additional circular-polarization converters are bulky and hardly compatible with nanophotonic circuits, and most active chiral plasmonic nanostructures nowadays exhibit broadband emission and low circular dichroism. In this work, with spirals of gallium nitride (GaN) nanowires (NWRs) covered by a metal layer, we demonstrated an ultrasmall semiconductor laser capable of emitting circularly-polarized photons. The left- and right-hand spiral metal nanowire cavities with varied periods were designed at ultraviolet wavelengths to achieve the high quality factor circular dichroism metastructures. The dissymmetry factors characterizing the degrees of circular polarizations of the left- and right-hand chiral lasers were 1.4 and −1.6 (±2 if perfectly circular polarized), respectively. The results show that the chiral cavities with only 5 spiral periods can achieve lasing signals with the high degrees of circular polarizations.

A Practical Guide for Predicting the Stereochemistry of Bifunctional Phosphoric Acid Catalyzed Reactions of Imines.

Chiral phosphoric acids have become powerful catalysts for the stereocontrolled synthesis of a diverse array of organic compounds. Since the initial report, the development of phosphoric acids as catalysts has been rapid, demonstrating the tremendous generality of this catalyst system and advancing the use of phosphoric acids to catalyze a broad range of asymmetric transformations ranging from Mannich reactions to hydrogenations through complementary modes of activation. These powerful applications have been developed without a clear mechanistic understanding of the reasons for the high level of stereocontrol. This Account describes investigations into the mechanism of the phosphoric acid catalyzed addition of nucleophiles to imines, focusing on binaphthol-based systems. In many cases, the hydroxyl phosphoric acid can form a hydrogen bond to the imine while the P═O interacts with the nucleophile. The single catalyst, therefore, activates both the electrophile and the nucleophile, while holding both in the chiral pocket created by the binaphthol and constrained by substituents at the 3 and 3' positions. Detailed geometric and energetic information about the transition states can be gained from calculations using ONIOM methods that combine the advantages of DFT with some of the speed of force fields. These high-level calculations give a quantitative account of the selectivity in many cases, but require substantial computational resources. A simple qualitative model is a useful complement to this complex quantitative model. We summarize our calculations into a working model that can readily be sketched by hand and used to work out the likely sense of selectivity for each reaction. The steric demands of the different parts of the reactants determine how they fit into the chiral cavity and which of the competing pathways is favored. The preferred pathway can be found by considering the size of the substituents on the nitrogen and carbon atoms of the imine electrophile, and the position of the nucleophilic site on the nucleophile in relation to the hydrogen-bond which holds it in the catalyst active site. We present a guide to defining the pathway in operation allowing the fast and easy prediction of the stereochemical outcome and provide an overview of the breadth of reactions that can be explained by these models including the latest examples.