Chirality Induction and Memory of Pillar[4]arene[1]quinone Derivatives in Visible-Light Range.

Pillar[4]arene[1]quinone derivatives (PQXs) were synthesized by the oxidation of pillar[5]arenes, which exhibited notable charge transfer (CT) transitions at approximately 485 nm. Successful chiral resolution of two pairs of enantiomeric conformers was achieved. Despite reduced binding affinity, PQXs demonstrated slower racemization kinetics. Visible-light chiroptical induction with a significant dissymmetry factor was attained by complexing PQXs with a chiral guest. The induced enantiomeric excess could be maintained through competitive binding with an achiral guest, offering a promising strategy for chiral sensing and memory.

Homomultivalent Polymeric Nanotraps Disturb Lipid Metabolism Homeostasis and Tune Pyroptosis in Cancer.

Genetic manipulations and pharmaceutical interventions to disturb lipid metabolism homeostasis have emerged as an attractive approach for the management of cancer. However, the research on the utilization of bioactive materials to modulate lipid metabolism homeostasis remains constrained. In this study, heptakis (2,3,6-tri-O-methyl)-ß-cyclodextrin (TMCD) is utilized to fabricate homomultivalent polymeric nanotraps, and surprisingly, its unprecedented ability to perturb lipid metabolism homeostasis and induce pyroptosis in tumor cells is found. Through modulation of the density of TMCD arrayed on the polymers, one top-performing nanotrap, PTMCD4, exhibits the most powerful cholesterol-trapping and depletion capacity, thus achieving prominent cytotoxicity toward different types of tumor cells and encouraging antitumor effects in vivo. The interactions between PTMCD4 and biomembranes of tumor cells effectively enable the reduction of cellular phosphatidylcholine and cholesterol levels, thus provoking damage to the biomembrane integrity and perturbation of lipid metabolism homeostasis. Additionally, the interplays between PTMCD4 and lysosomes also induce lysosomal stress, activate the nucleotide-binding oligomerization domain-like receptor protein 3 inflammasomes, and subsequently trigger tumor cell pyroptosis. To sum up, this study first introduces dendronized bioactive polymers to manipulate lipid metabolism and has shed light on another innovative insight for cancer therapy.

Asymmetric Photoreactions in Supramolecular Assemblies.

ConspectusStereochemical control of excited-state asymmetric photoreactions has been one of the most challenging topics of modern photochemistry. The short-lived character of electronically excited photosubstrates and their low activation energy barriers to form both enantiomers are the major obstacles to achieving significant enantioselectivity in excited-state asymmetric photochemistry. Recent research demonstrated that the supramolecular strategy is promising to control the stereochemical outcome of asymmetric photoreaction through relatively strong and long-lasting noncovalent interaction at both ground and excited states. In this methodology, chiral hosts/assemblies provide the chiral environment for photochemically transferring chirality to the complexed photosubstrate in both the ground and the excited states by virtue of relatively strong supramolecular interactions, such as hydrogen bonding, van der Waals, π-π, electrostatic, and hydrophobic interactions. The orientation and conformation of the photosubstrate can be critically manipulated by the supramolecular complexation to ensure the subsequent effective stereoselective photochemical conversion.This Account describes our recent advance in asymmetric photoreactions in supramolecular assemblies. Several chiral photoreactions, including photoisomerization of cycloolefins and photocyclodimerization of anthracene and naphthalene derivatives, have been mediated by various supramolecular hosts, such as cyclodextrin (CD), cucurbituril, pillararene, and chiral polymer. The following advantages of supramolecular asymmetric photochemistry were evidenced: (1) The improvement of stereoselectivity can be enabled by the careful design and fabrication of chiral host molecules. (2) Supramolecular complexation could effectively regulate the orientation and conformation of photosubstrates, thus resulting in novel reaction pathways which create unusual photoproducts that are not achievable through traditional reaction conditions. (3) Asymmetric photoreactions in supramolecular systems showed strong correlations with the external environmental variants, such as temperature, solvent, irradiation wavelength, and pressure, which therefore provide a powerful tool for the regulation of stereoselectivities of excited-state photoreactions. (4) Utilizing supramolecular complexation can dramatically speed up photoreactions, a combination of appropriate photosensitizers/photocatalysts being able to drive catalyzed chiral photoreactions effectively. (5) Photoisomerization in chiral supramolecular systems has been applied to chiroptical molecular devices, which exhibited multiple stimulus-response functions and advanced switching performances. We believe that these concepts, methods, and principles derived therefrom are instructive in designing chiral supramolecular hosts, elucidating the stereodifferentiation mechanisms in the ground and excited states, and analyzing and improving the stereochemical outcomes of a diverse range of supramolecular chiral photoreactions.

Chiroptical induction with prism[5]arene alkoxy-homologs.

The complexation of prism[5]arenes with amino acid derivatives showed association constants of up to 107 M-1, significant CD with gabs of up to 0.8 × 10-2 and CPL with glum of 2 × 10-3. The absolute configuration-CD signal correlation was established. The CD spectra varied significantly with the substituents on the prism[5]arenes.

Unveiling the Accelerated Water Electrolysis Kinetics of Heterostructural Iron-Cobalt-Nickel Sulfides by Probing into Crystalline/Amorphous Interfaces in Stepwise Catalytic Reactions.

Amorphization and crystalline grain boundary engineering are adopted separately in improving the catalytic kinetics for water electrolysis. Yet, the synergistic effect and advance in the cooperated form of crystalline/amorphous interfaces (CAI) have rarely been elucidated insightfully. Herein, a trimetallic FeCo(NiS2 )4 catalyst with numerous CAI (FeCo(NiS2 )4 -C/A) is presented, which shows highly efficient catalytic activity toward both hydrogen and oxygen evolution reactions (HER and OER). Density functional theory (DFT) studies reveal that CAI plays a significant role in accelerating water electrolysis kinetics, in which Co atoms on the CAI of FeCo(NiS2 )4 -C/A catalyst exhibit the optimal binding energy of 0.002 eV for H atoms in HER while it also has the lowest reaction barrier of 1.40 eV for the key step of OER. H2 O molecules are inclined to be absorbed on the interfacial Ni atoms based on DFT calculations. As a result, the heterostructural CAI-containing catalyst shows a low overpotential of 82 and 230 mV for HER and OER, respectively. As a bifunctional catalyst, it delivers a current density of 10 mA cm-2 at a low cell voltage of 1.51 V, which enables it a noble candidate as metal-based catalysts for water splitting. This work explores the role of CAI in accelerating the HER and OER kinetics for water electrolysis, which sheds light on the development of efficient, stable, and economical water electrolysis systems by facile interface-engineering implantations.

Synthesis of cyclodextrin derivatives for enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylate.

Photochemical methods are increasingly being used in organic synthesis. They are especially useful for preparing many compounds that are not readily accessible through thermal or enzymatic reactions. The supramolecular strategy has proved highly promising in recent years for manipulating the stereochemical outcome of chiral photoreactions through relatively strong and long-lasting noncovalent interactions in both ground and excited states. Among the numerous chiral photochemical reactions, photocyclodimerization of 2-anthracenecarboxylate (AC) is the most comprehensively studied supramolecular chiral photoreaction and has essentially become a benchmark reaction for evaluating supramolecular photochirogenesis. Cyclodextrin (CD) derivatives were the earliest and are the most widely applied chiral host for mediating photoreactions. Herein, we use CD-mediated photocyclodimerization of AC as an example to introduce the operation process of supramolecular chiral photoreactions. The protocol includes the following contents: (i) the preparation, purification and characterization of ß-CD derivatives; (ii) methods for investigating the host-guest inclusion behavior between AC and ß-CD derivatives; (iii) the photochemical reaction operation flow under different solvent and temperature conditions; (iv) chiral high-performance liquid chromatography (HPLC) analyses of the product distribution and enantioselectivity. The protocol is introduced by using representative examples of the synthesis of ß-CD derivatives and the manipulation of environmental factors that give excellent regio- and enantioselectivities in the photocyclodimerization of AC. The synthesis and purification of ß-CD derivatives require 3-5 d of work. The photoirradiation of AC with ß-CD derivatives can be done within 1 h. The product analysis requires 5 h.

Catalytic Chiral Photochemistry Sensitized by Chiral Hosts-Grafted Upconverted Nanoparticles.

Singlet chiral photocatalysis is highly challenging. Herein, we report fluorescence resonance energy transfer (FRET)-based chiral photocatalysis with γ-cyclodextrin (CD)-grafted lanthanide-doped upconverted nanoparticles (UCNP). The CD-modified UCNP strongly emits in the UV wavelength region upon excitation with a 980 nm laser, which selectively sensitizes the photosubstrates complexed by CD on the surface of UCNP through FRET. Therefore, enantiodifferentiating photocyclodimerization of anthracene or naphthalene derivatives sensitized by the CD-modified UCNP gives photoproducts in good enantioselectivity even in the presence of a catalytic amount of CD-modified UCNP. Moreover, the photocatalysts are readily separated and could be reused for at least six cycles without decreasing the enantioselectivity.

The More the Slower: Self-Inhibition in Supramolecular Chirality Induction, Memory, Erasure, and Reversion.

Self-inhibition has been observed widely in hierarchical biochemical processes but has yet to be demonstrated in pure molecular physical rather than chemical or biological processes. Herein, we report an unprecedented example of self-inhibition during the supramolecular chirality induction, memory, erasure, and inversion processes of pillar[5]arene (P[5]) derivatives. The addition of chiral alanine ethyl ester to bulky substituent-modified P[5]s led to time-dependent chirality induction due to the shift in the equilibrium of the SP and RP conformers P[5]. Intriguingly, more chiral inducers led to more intensive final chiroptical properties but lower chiral induction rates. Thus, the chiral inducer plays the role of both activator and inhibitor. Such self-inhibition essentially arises from kinetics manipulation of three tandem equilibria. Moreover, the chiroptical properties could be memorized by replacing the chiral inducer with an achiral competitive binder, and the chiroptical signal could be erased and reversed by an antipodal chiral inducer, which also showed the self-inhibition property.

Supramolecular Enantiodifferentiating Photocyclodimerization of 2-Anthracenecarboxylic Acid Mediated by Bridged ß-Cyclodextrins: Critical Effects of the Host Structure, pH and Co-Solvents.

Several sulfoxide- and sulfone-bridged ß-cyclodextrin (CD) dimers were synthesized for mediating the enantiodifferentiating [4+4] photocyclodimerization of 2-anthracenecarboxylic acid (AC). The complexation behavior of these chiral hosts with AC was investigated by UV-vis, circular dichroism, fluorescence, and NMR spectroscopies and certified the formation of 1 : 1 and 1 : 2 host-guest complexes. The product distribution and enantioselectivity of the photoreaction turned out to be a critical function of the chemical structure of bridged CDs. Comparing to the sulfur-bridged 2AX -3GX ß-CD dimer 7, the conversion of the photolyzes with sulfoxide-bridged was significantly improved, and the ee of cyclodimer 2 was remarkably increased from -82.8% with 7 to -96.7% with the sulfoxide-bridged 2AX -3GX ß-CD dimer 8. The relative yields and ee values of the slipped cyclodimers 5 and 6 were greatly enhanced in the presence of 6 M CsCl. The reaction selectivity is susceptible to the pH variation of the aqueous buffer solution, demonstrating that the supramolecular photochirogenesis is controlled by multidimensional factors, including the chemical structure of the chiral host, solvent, and pH conditions.

Solvent-Driven Chirality Switching of a Pillar[4]arene[1]quinone Having a Chiral Amine-Substituted Quinone Subunit.

Several new chiral pillar[4]arene[1]quinone derivatives were synthesized by reacting pillar[4]arene[1]quinone (EtP4Q1), containing four 1,4-diethoxybenzene units and one benzoquinone unit, with various chiral amines via Michael addition. Due to the direct introduction of chiral substituents on the rim of pillar[n]arene and the close location of the chiral center to the rim of EtP4Q1, the newly prepared compounds showed unique chiroptical properties without complicated chiral resolution processes, and unprecedented high anisotropy factor of up to -0.018 at the charge transfer absorption band was observed. Intriguingly, the benzene sidearm attached pillar[4]arene[1]quinone derivative 1a showed solvent- and complexation-driven chirality inversion. This work provides a promising potential for absolute asymmetric synthesis of pillararene-based derivatives.

Chiroptical Sensing of Amino Acid Derivatives by Host-Guest Complexation with Cyclo[6]aramide.

A hydrogen-bonded (H-bonded) amide macrocycle was found to serve as an effective component in the host-guest assembly for a supramolecular chirality transfer process. Circular dichroism (CD) spectroscopy studies showed that the near-planar macrocycle could produce a CD response when combined with three of the twelve L-α-amino acid esters (all cryptochiral molecules) tested as possible guests. The host-guest complexation between the macrocycle and cationic guests was explored using NMR, revealing the presence of a strong affinity involving the multi-point recognition of guests. This was further corroborated by density functional theory (DFT) calculations. The present work proposes a new strategy for amplifying the CD signals of cryptochiral molecules by means of H-bonded macrocycle-based host-guest association, and is expected to be useful in designing supramolecular chiroptical sensing materials.

Synergetic effects in the enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylic acid mediated by ß-cyclodextrin-pillar[5]arene-hybridized hosts.

Tri-cavity hosts consisting of one pillar[5]arene (P5) sandwiched by two ß-cyclodextrins (CDs) were synthesized, and their diastereoseparation was successfully accomplished. Photocyclodimerization of 2-anthracenecarboxylate with these hybrid hosts demonstrated the critical dependence of stereoselectivity on the absolute configuration of the central P5 and the conjugating positions on the ß-CD, and gave the non-classical HT photodimers in up to 87% ee.

pH-Controlled Chirality Inversion in Enantiodifferentiating Photocyclodimerization of 2-Antharacenecarboxylic Acid Mediated by γ-Cyclodextrin Derivatives.

Several γ-cyclodextrin (γ-CDx) derivatives were used as chiral hosts for the photocyclodimerization of 2-anthracenecarboxylic acid (AC). The effect of pH on photoreactivity and stereochemical outcome of photoproducts was investigated. Upon changing the solution pH, the stereochemical outcome of HH cyclodimer 3 was inverted from 25.2% to -64.4% and 41.2% to -76.2%, respectively, in the photocyclodimerization of AC mediated by bis-quinoline-modified γ-CDx 7 and its N-methylated derivative 8.

Supramolecular enantiomeric and structural differentiation of amino acid derivatives with achiral pillar[5]arene homologs.

Complexation of achiral pillar[5]arenes with chiral amines induced strong circular dichroism (CD) signals. The CD responses differed drastically depending on the nature of the amino acid guest, and they significantly varied and part of them even inverted, upon increasing the length of the alkyl chains of the pillar[5]arenes guests. Accordingly, this tactic allowed for the unprecedented simultaneous enantiomeric and structural differentiation of α-amino esters with homologous molecular hosts.

Reversal of Regioselectivity during Photodimerization of 2-Anthracenecarboxylic Acid in a Water-Soluble Organic Cavitand.

The value of octa acid (OA) as a reaction vessel in steering a photoreaction toward a less favored product was established. Photodimerization of 2-anthracenecarboxylic acid within OA yields exclusively head-to-head dimers, while in media such as solution, cyclodextrins (CD) and related hosts yield predominantly head-to-tail dimers. Further, OA enhances the chiral selectivity on the product dimers. The difference between OA and CD is attributed to the variation in the dimensions of their entry ports.

An Ultimate Stereocontrol in Supramolecular Photochirogenesis: Photocyclodimerization of 2-Anthracenecarboxylate Mediated by Sulfur-Linked ß-Cyclodextrin Dimers.

Stereoisomeric ß-cyclodextrin (CD) dimers linked with a sulfur atom or an arene spacer were designed to create a tethered dual CD capsule for precisely manipulating the regio- and enantioselectivities of the photocyclodimerization of 2-anthracenecarboxylate (AC) to four stereoisomeric classical 9,10:9',10'-cyclodimers and two nonclassical 5,8:9',10'-cyclodimers. Among the dimeric CD hosts prepared, exo-3-thia-ß-CD dimer formed 1:1 and 1:2 host-guest complexes with AC in aqueous solutions, the former of which hindered but the latter facilitated the AC photocyclodimerization with regio- and enantioselectivities much higher than those obtained with native ß-CD or the rest of the ß-CD dimers. The stereochemical outcomes turned out to be highly sensitive to and hence critically manipulable by the linking position and configuration of the connected saccharide units and the linker length, as well as the external variants, such as temperature, pH, and added salt. Eventually, the photocyclodimerization of AC mediated by the dimeric ß-CD host gave enantiopure syn-head-to-tail-9,10:9',10'-cyclodimer in 97-98% yield in a pH 5.1 buffer solution at 0.5 °C and also in an aqueous CsCl solution at -20 °C.

Induced chirality sensing through formation and aggregation of the chiral imines double winged with pyrenes or perylenes.

Reaction of chiral amines with benzaldehydes 3,5-disubstituted by two pyrenes or perylenes afforded corresponding double winged chiral imines, which aggregated to show significantly enhanced circular dichroism spectra at the transition bands of the chromophores in the mixture solutions of DMF and H2O.

Photocatalytic Supramolecular Enantiodifferentiating Dimerization of 2-Anthracenecarboxylic Acid through Triplet-Triplet Annihilation.

Visible-light-driven enantiodifferentiating photodimerization of 2-anthracenecarboxylic acid (AC) sensitized by Schiff base Pt(II) complex-grafted γ-cyclodextrins leads the first triplet-triplet annihilation-based catalytic photochirogenesis. The syn-head-to-tail (HT) photodimer 2 was achieved in up to 31.4% ee at 61.0% conversion in the presence of 0.5% equiv of the photocatalyst.

Enhanced chiral recognition by γ-cyclodextrin-cucurbit[6]uril-cowheeled [4]pseudorotaxanes.

Mixing γ-cyclodextrin (γ-CD), cucurbit[6]uril (CB[6]) and tetraammonium-bearing axles together led to a spontaneous formation of γ-CD-CB[6]-cowheeled [4]pseudorotaxanes. The well-defined unsymmetrical cavities thus formed enhance the binding affinity towards chiral amines by factors of several hundreds and show remarkably improved chiral discrimination.

Ammonia-driven chirality inversion and enhancement in enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylate mediated by diguanidino-γ-cyclodextrin.

In the supramolecular photocyclodimerization of 2-anthracenecarboxylate mediated by 6(A),6(D)-diguanidino-γ-cyclodextrin (CD), the chiral sense and enantiomeric excess of the photoproduct were dynamic functions of temperature and cosolvent to afford the (M)-anti head-to-head cyclodimer in 64% ee in aqueous methanol at -70 °C but the antipodal (P)-isomer in 86% ee in aqueous ammonia at -85 °C, while the corresponding diamino-γ-CD host did not show such unusual photochirogenic behaviors. The ee landscape was very steep against the temperature and sign-inverted against the ammonia content to reveal the opposite temperature dependence at low and high ammonia contents, for which an altered solvent structure and/or guanidinium-carboxylate interaction mode would be responsible.