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.     

A host–guest strategy for converting the photodynamic agents from a singlet oxygen generator to a superoxide radical generator

Type-I photosensitizers (PSs) generate cytotoxic oxygen radicals by electron transfer even in a hypoxic environment. Nevertheless, the preparation of type-I PSs remains a challenge due to the competition of triplet–triplet energy transfer with O₂ (type-II process). In this work, we report an effective strategy for converting the conventional type-II PS to a type-I PS by host–guest complexation. Electron-rich pillar[5]arenes are used as an electron donor and macrocyclic host to produce a host–guest complex with the traditional electron-deficient type-II PS, an iodide BODIPY-based guest. The host–guest complexation promotes intermolecular electron transfer from the pillar[5]arene moiety to BODIPY and then to O₂ by the type-I process upon light-irradiation, leading to efficient generation of the superoxide radical (O₂⁻˙). The results of anti-tumor studies indicate that this supramolecular PS demonstrates high photodynamic therapy efficacy even under hypoxic conditions. This work provides an efficient method to prepare type-I PSs from existing type-II PSs by using a supramolecular strategy.

A supramolecular strategy is reported for converting the conventional photodynamic agents from a singlet oxygen generator to a superoxide radical generator by the host–guest interaction enhanced electron transfer.     

Reconstructing reactivity in dynamic host–guest systems at atomistic resolution: amide hydrolysis under confinement in the cavity of a coordination cage

Spatial confinement is widely employed by nature to attain unique efficiency in controlling chemical reactions. Notable examples are enzymes, which selectively bind reactants and exquisitely regulate their conversion into products. In an attempt to mimic natural catalytic systems, supramolecular metal–organic cages capable of encapsulating guests in their cavity and of controlling/accelerating chemical reactions under confinement are attracting increasing interest. However, the complex nature of these systems, where reactants/products continuously exchange in-and-out of the host, makes it often difficult to elucidate the factors controlling the reactivity in dynamic regimes. As a case study, here we focus on a coordination cage that can encapsulate amide guests and enhance their hydrolysis by favoring their mechanical twisting towards reactive molecular configurations under confinement. We designed an advanced multiscale simulation approach that allows us to reconstruct the reactivity in such host–guest systems in dynamic regimes. In this way, we can characterize amide encapsulation/expulsion in/out of the cage cavity (thermodynamics and kinetics), coupling such host–guest dynamic equilibrium with characteristic hydrolysis reaction constants. All computed kinetic/thermodynamic data are then combined, obtaining a statistical estimation of reaction acceleration in the host–guest system that is found in optimal agreement with the available experimental trends. This shows how, to understand the key factors controlling accelerations/variations in the reaction under confinement, it is necessary to take into account all dynamic processes that occur as intimately entangled in such host–guest systems. This also provides us with a flexible computational framework, useful to build structure–dynamics–property relationships for a variety of reactive host–guest systems.

Encapsulation of guests in metal–organic cages allows control over chemical reactivity. Focusing on the hydrolysis of amides, here we show an effective molecular simulation approach to reconstruct reactivity in host–guest systems in dynamic regimes.     

Unexpected chirality transition and inversion mediated by dissolution–aggregation and the odd–even effect

The evolution of hierarchical chirality at macromolecular and supramolecular levels in biological systems is ubiquitous; however, achieving precise control over transitions between them in polymer systems is still challenging. Here, we reported multiple chiroptical transitions and inversion phenomena in side-chain azobenzene (Azo) polymers, PAzo-l/d-m (m = 3, 6, 7, 8, 9, and 10, where m is the total number of atoms from the chiral stereocenter to the Azo unit), with different distances from the chiral stereocenter to the Azo unit. In the case of m = 3, an unexpected macromolecular-to-supramolecular chirality transition and inversion occurred in situ when the Azo-polymer underwent from a macromolecular-dissolved state to a supramolecular-aggregated state. To our surprise, an exciton-coupling induced multiple chiroptical inversion was observed upon the heating-assisted reassembly treatment, which was demonstrated to be driven by H- to J-aggregation transition. Furthermore, the odd–even effect was first established to regulate the supramolecular helical orientations (left- or right-handedness) in side-chain Azo-polymer assemblies.

Unexpected chirality transition and inversion at molecular, macromolecular and supramolecular levels were realized by dissolution–aggregation and the odd–even effect, which is helpful for the design of advanced chirality-controllable materials.     

Chiral molecular nanosilicas

Molecular nanoparticles including polyoxometalates, proteins, fullerenes and polyhedral oligosiloxane (POSS) are nanosized objects with atomic precision, among which POSS derivatives are the smallest nanosilicas. Incorporation of molecular nanoparticles into chiral aggregates either by chiral matrices or self-assembly allows for the transfer of supramolecular chirality, yet the construction of intrinsic chirality with atomic precision in discrete molecules remains a great challenge. In this work, we present a molecular folding strategy to construct giant POSS molecules with inherent chirality. Ferrocenyl diamino acids are conjugated by two or four POSS segments. Hydrogen bonding-driven folding of diamino acid arms into parallel β-sheets facilitates the chirality transfer from amino acids to ferrocene and POSS respectively, disregarding the flexible alkyl spacers. Single crystal X-ray structures, density functional theory (DFT) calculations, circular dichroism and vibrational circular dichroism spectroscopy clearly verify the preferential formation of one enantiomer containing chiral molecular nanosilicas. The chiral orientation and chiroptical properties of POSS show pronounced dependence on the substituents of α-amino acids, affording an alternative way to control the folding behavior and POSS chirality in addition to the absolute configuration of amino acids. Through the kinetic nanoprecipitation protocol, one-dimensional aggregation enables chirality transfer from the molecular scale to the micrometer scale, self-assembling into helices in accordance with the packing propensity of POSS in a crystal phase. This work, by illustrating the construction of chiral molecular nanosilicas, paves a new way to obtain discrete chiral molecular nanoparticles for potential chiroptical applications.

A molecular folding strategy is developed to construct ferrocenyl diamino acid conjugated polyhedral oligosiloxane molecules. Hydrogen bonding-driven folding facilitates the chirality transfer from the molecular scale to the micrometer scale.     

Elucidating dissociation activation energies in host–guest assemblies featuring fast exchange dynamics

The ability to mediate the kinetic properties and dissociation activation energies (E_a) of bound guests by controlling the characteristics of “supramolecular lids” in host–guest molecular systems is essential for both their design and performance. While the synthesis of such systems is well advanced, the experimental quantification of their kinetic parameters, particularly in systems experiencing fast association and dissociation dynamics, has been very difficult or impossible with the established methods at hand. Here, we demonstrate the utility of the NMR-based guest exchange saturation transfer (GEST) approach for quantifying the dissociation exchange rates (k_out) and activation energy (E_a,out) in host–guest systems featuring fast dissociation dynamics. Our assessment of the effect of different monovalent cations on the extracted E_a,out in cucurbit[7]uril:guest systems with very fast k_out highlights their role as “supramolecular lids” in mediating a guest''s dissociation E_a. We envision that GEST could be further extended to study kinetic parameters in other supramolecular systems characterized by fast kinetic properties and to design novel switchable host–guest assemblies.

GEST-NMR is utilized for quantifying the dissociation activation energy (E_a,out) in host-guest systems featuring fast dissociation dynamics.     

Engineering living cells with cucurbit[7]uril-based supramolecular polymer chemistry: from cell surface engineering to manipulation of subcellular organelles

Supramolecular polymer chemistry, which closely integrates noncovalent interactions with polymeric structures, is a promising toolbox for living cell engineering. Here, we report our recent progress in exploring the applications of cucurbit[7]uril (CB[7])-based supramolecular polymer chemistry for engineering living cells. First, a modular polymer-analogous approach was established to prepare multifunctional polymers that contain CB[7]-based supramolecular recognition motifs. The supramolecular polymeric systems were successfully applied to cell surface engineering and subcellular organelle manipulation. By anchoring polymers on the cell membranes, cell–cell interactions were established by CB[7]-based host–guest recognition, which further facilitated heterogeneous cell fusion. In addition to cell surface engineering, placing the multifunctional polymers on specific subcellular organelles, including the mitochondria and endoplasmic reticulum, has led to enhanced physical contact between subcellular organelles. It is highly anticipated that the CB[7]-based supramolecular polymer chemistry will provide a new strategy for living cell engineering to advance the development of cell-based therapeutic materials.

Cucurbit[7]uril-based supramolecular polymer chemistry, which closely integrates host–guest recognition with multifunctional polymeric structures, is a promising toolbox for living cell engineering.     

Axially chiral indolenine derived chromophore dimers and their chiroptical absorption and emission properties

Yamamoto homocoupling of two chiral oxindoles led to the atropo-diastereoselective formation of an axially chiral oxindole dimer. This building block served as the starting material for the syntheses of axially chiral squaraine and merocyanine chromophore dimers. These dimers show pronounced chiroptical properties, this is, outstandingly high ECD signals (Δε up to ca. 1500 M⁻¹ cm⁻¹) as a couplet with positive Cotton effect for the P-configuration around the biaryl axis and a negative Cotton effect for the M-configuration. All investigated dimers also exhibit pronounced circularly polarised emission with anisotropy values of ca. 10⁻³ cgs. Time-dependent density functional calculations were used to analyse the three contributions (local one electron, electric–magnetic coupling, and exciton coupling) to the rotational strength applying the Rosenfeld equation to excitonically coupled chromophores. While the exciton coupling term proves to be the dominant one, the electric–magnetic coupling possesses the same sign and adds significantly to the total rotational strength owing to a favourable geometric arrangement of the two chromophores within the dimer.

From an axially chiral oxindole, squaraine and merocyanine chromophore dimers with pronounced chiroptical properties were prepared.     

Influence of the chemical structure of water-soluble cryptophanes on their overall chiroptical and binding properties

The synthesis and the chiroptical properties of the two enantiomers of the hexacarboxylic acid cryptophane-A derivative, 1, are described in this article. The chiroptical and binding properties of 1 toward achiral and chiral guests have been investigated in water under basic conditions by polarimetry, electronic circular dichroism (ECD), vibrational circular dichroism (VCD), and (1)H NMR spectroscopy. These experiments reveal that the (1)H NMR spectra of 1 are very sensitive to the nature of the guest trapped in its cavity whereas ECD and VCD spectra remain unchanged. We also show that the two enantiomers of 1 are able to distinguish between the two enantiomers of a series of small chiral epoxides. The enantiodiscrimination increases with the size of the chiral guest whereas the corresponding binding constants decrease. In contrast to what was observed for other water-soluble cryptophanes, the molecular recognition process is found independent of the nature of the counterions surrounding host 1, shedding light on the importance of the chemical structure of cryptophanes on their binding and chiroptical properties.     

Modular and hierarchical self-assembly of siRNAs into supramolecular nanomaterials for soft and homogeneous siRNA loading and precise and visualized intracellular delivery

siRNA therapeutics are challenged by homogeneous and efficient loading, maintenance of biological activities, and precise, dynamic and monitorable site-release. Herein, supramolecular nanomaterials of WP5⊃G–siRNA were constructed by modular and hierarchical self-assembly of siRNA with guest (3,6-di(thiophen-2-yl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione derivative, G) and host (pillar[5]arene, WP5) molecules in the same system. Demonstrated by experiments and theoretical calculations, WP5⊃G–siRNA was constructed via comprehensive weak interactions including electrostatic, hydrophobic–hydrophilic, host–guest and π–π interactions. Therefore, siRNAs were efficiently loaded, maintaining good stability, bioactivities and biocompatibilities. At pH 6.8, G was protonated to give weak acidic-responsive “turn-on” fluorescent signals, which realized the precise location of cancer sites. This triggered a subsequent delivery and a dynamic release of siRNA in cancer cells under acidic conditions for the entire collapse of WP5⊃G–siRNA by the protonation of both WP5 and G. By both in vitro and in vivo experiments, precise and visualized delivery to cancer sites was achieved to exhibit effective tumour inhibition. This provided an efficient and soft strategy of siRNA therapies and expanded the application of supramolecular nanomaterials in diagnosis and treatment.

Supramolecular nanomaterials of WP5⊃G–siRNA were constructed by modular and hierarchical self-assembly of siRNA with guest and host molecules, initiating weak acidic-responsive, precise and visualized intracellular delivery for efficient therapies.     

Docking rings in a solid: reversible assembling of pseudorotaxanes inside a zirconium metal–organic framework

An unprecedented zirconium metal–organic framework featuring a T-shaped benzimidazole strut was constructed and employed as a sponge-like material for selective absorption of macrocyclic guests. The neutral benzimidazole domain of the as-synthesized framework can be readily protonated and fully converted to benzimidazolium. Mechanical threading of [24]crown-8 ether wheels onto recognition sites to form pseudorotaxanes was evidenced by solution nuclear magnetic resonance, solid-state fluorescence, and infrared spectroscopy. Selective absorption of [24]crown-8 ether rather than its dibenzo counterpart was also observed. Further study reveals that this binding process is reversible and acid–base switchable. The success of docking macrocyclic guests in crystals via host–guest interactions provides an alternative route to complex functional materials with interpenetrated structures.

A T-shaped ligand was designed as struts for building a zirconium metal–organic framework. Acid–base switchable docking and releasing a 24-membered crown ether inside crystals was successfully accomplished via post-synthetic modification.     

应用电子圆二色光谱方法确定手性金属配合物的绝对构型

与电子能级跃迁相关的电子圆二色(ECD)光谱因其研究对象宽泛,与涉及振动能级的振动圆二色(VCD)光谱互补,已成为应用于手性立体化学研究的集成手性光谱的主流表征手段。本文概述了确定手性金属配合物绝对构型的三种主要方法,详细介绍了ECD光谱法在确定手性金属配合物绝对构型中的应用,其中着重强调了激子手性方法,并对集成手性光谱学未来的发展趋势做出了展望。     

Enantioselective assembly and recognition of heterochiral porous organic cages deduced from binary chiral components

Chiral recognition and discrimination is not only of significance in biological processes but also a powerful method to fabricate functional supramolecular materials. Herein, a pair of heterochiral porous organic cages (HPOC-1), out of four possible enantiomeric products, with mirror stereoisomeric crystal structures were cleanly prepared by condensation occurring in the exclusive combination of cyclohexanediamine and binaphthol-based tetraaldehyde enantiomers. Nuclear magnetic resonance and luminescence spectroscopy have been employed to monitor the assembly process of HPOC-1, revealing the clean formation of heterochiral organic cages due to the enantioselective recognition of (S,S)-binaphthol towards (R,R)-cyclohexanediamine derivatives and vice versa. Interestingly, HPOC-1 exhibits circularly polarized luminescence and enantioselective recognition of chiral substrates according to the circular dichroism spectral change. Theoretical simulations have been carried out, rationalizing both the enantioselective assembly and recognition of HPOC-1.

Heterochiral organic cages based on enantioselective self-assembly of binary chiral components have been prepared, exhibiting circularly polarized luminescence property and enantioselective recognition ability towards chiral substrates according to the circular dichroism spectral change.     

Cucurbiturils brighten Au nanoclusters in water

Gold nanoclusters (AuNCs) with well-defined atomically precise structures present promising emissive prospects for excellent biocompatibility and optical properties. However, the relatively low luminescence efficiency in solutions for most AuNCs is still a perplexing issue to be resolved. In this study, a facile supramolecular strategy was developed to rigidify the surface of FGGC-AuNCs by modifying transition rates in excited states via host–guest self-assembly between cucurbiturils (CBs) and FGGC (Phe–Gly–Gly–Cys peptide). In aqueous solutions, CB/FGGC-AuNCs presented an extremely enhanced red phosphorescence emission with a quantum yield (QY) of 51% for CB[7] and 39% for CB[8], while simple FGGC-AuNCs only showed a weak emission with a QY of 7.5%. Furthermore, CB[7]/FGGC-AuNCs showed excellent results in live cell luminescence imaging for A549 cancer cells. Our study demonstrates that host–guest self-assembly assisted by macrocycles is a facile and effective tool to non-covalently modify and adjust optical properties of nanostructures on ultra-small scales.

A host–guest self-assembly approach was developed to brighten Au₂₂(FGGC)₁₈ nanoclusters between CB[n] (n = 7, 8) and FGGC peptide in aqueous solutions.     

Preparation of cruciferous phytoalexin related metabolites, (−)-dioxibrassinin and (−)-3-cyanomethyl-3-hydroxyoxindole, and determination of their absolute configurations by vibrational circular dichroism (VCD)

Cruciferous phytoalexin related metabolites, (−)-dioxibrassinin (1) and (−)-3-cyanomethyl-3-hydroxyoxindole (2) were prepared from isatin as racemates and were resolved by chiral HPLC. Their absolute configurations were determined by the new chiroptical technique, vibrational circular dichroism (VCD), as well as by the conventional electronic circular dichroism (ECD). It is concluded that the absolute configurations of the naturally occurring (−)-1 and (−)-2 are both S.     

Lanthanide MOFs for inducing molecular chirality of achiral stilbazolium with strong circularly polarized luminescence and efficient energy transfer for color tuning

We present herein an innovative host–guest method to achieve induced molecular chirality from an achiral stilbazolium dye (DSM). The host–guest system is exquisitely designed by encapsulating the dye molecule in the molecule-sized chiral channel of homochiral lanthanide metal–organic frameworks (P-(+)/M-(−)-TbBTC), in which the P- or M-configuration of the dye is unidirectionally generated via a spatial confinement effect of the MOF and solidified by the dangling water molecules in the channel. Induced chirality of DSM is characterized by solid-state circularly polarized luminescence (CPL) and micro-area polarized emission of DSM@TbTBC, both excited with 514 nm light. A luminescence dissymmetry factor of 10⁻³ is obtained and the photoluminescence quantum yield (PLQY) of the encapsulated DSM in DSM@TbTBC is ∼10%, which is close to the PLQY value of DSM in dilute dichloromethane. Color-tuning from green to red is achieved, owing to efficient energy transfer (up to 56%) from Ln³⁺ to the dye. Therefore, this study for the first time exhibits an elegant host–guest system that shows induced strong CPL emission and enables efficient energy transfer from the host chiral Ln-MOF to the achiral guest DSM with the emission color tuned from green to red.

Homochiral Ln-MOFs are synthesized to encapsulate achiral dyes to induce strong circularly polarized luminescence with a luminescence dissymmetry factor of 10⁻³.     

Template-assisted self-assembly of achiral plasmonic nanoparticles into chiral structures

The acquisition of strong chiroptical activity has revolutionized the field of plasmonics, granting access to novel light–matter interactions and revitalizing research on both the synthesis and application of nanostructures. Among the different mechanisms for the origin of chiroptical properties in colloidal plasmonic systems, the self-assembly of achiral nanoparticles into optically active materials offers a versatile route to control the structure–optical activity relationships of nanostructures, while simplifying the engineering of their chiral geometries. Such unconventional materials include helical structures with a precisely defined morphology, as well as large scale, deformable substrates that can leverage the potential of periodic patterns. Some promising templates with helical structural motifs like liquid crystal phases or confined block co-polymers still need efficient strategies to direct preferential handedness, whereas other templates such as silica nanohelices can be grown in an enantiomeric form. Both types of chiral structures are reviewed herein as platforms for chiral sensing: patterned substrates can readily incorporate analytes, while helical assemblies can form around structures of interest, like amyloid protein aggregates. Looking ahead, current knowledge and precedents point toward the incorporation of semiconductor emitters into plasmonic systems with chiral effects, which can lead to plasmonic–excitonic effects and the generation of circularly polarized photoluminescence.

Diverse templating materials and assembly strategies can be used to induce collective optical activity on achiral plasmonic building blocks. We present the advances, applications, challenges, and prospects of plasmonic–excitonic hybrids.     

Caged bulky organic dyes in a polyaromatic framework and their spectroscopic peculiarities

Host–guest structures and properties have been widely studied using relatively small dyes (<1 nm) without bulky groups, due to their smooth incorporation, efficient host–guest interactions, and high analytical accessibility. In this report, on the other hand, three types of sterically demanding organic dyes trapped by a polyaromatic cage were investigated by spectroscopic analyses on the basis of supramolecular interactions. Coumarins with two bulky substituents are bound by the cage in aqueous solution. The resultant caged dyes show unusual emission enhancement, depending on the difference of a single heteroatom in their substituents. The color of perylene bisimides with two bulky substituents is remarkably changed from yellow to red upon caging. This peculiarity stems from the twist of the substituents in the cage, revealed by the combination of absorption and theoretical studies. Furthermore, tetrasubstituted, bulky porphyrins are caught by the cage in aqueous solution. The caged bulky dyes also display altered color and absorption properties, which remain intact even under acidic conditions. In contrast to typical covalent functionalization and previous host–guest studies toward small and non-bulky dyes, the unusual, non-covalent spectroscopic modulation of the large and bulky dyes can be accomplished for the first time by the present cage, featuring a prolate polyaromatic framework with four openings.

Here we report that the open large cavity of an M₂L₄ polyaromatic cage can efficiently bind sterically demanding organic dyes with coumarin, perylene bisimide, and porphyrin cores in aqueous solution. The spectroscopic properties of the caged dyes are largely modulated in the cavity.     

Encapsulation of Pt(iv) prodrugs within a Pt(ii) cage for drug delivery

This report presents a novel strategy that facilitates delivery of multiple, specific payloads of Pt(iv) prodrugs using a well-defined supramolecular system. This delivery system comprises a hexanuclear Pt(ii) cage that can host four Pt(iv) prodrug guest molecules. Relying on host–guest interactions between adamantyl units tethered to the Pt(iv) molecules and the cage, four prodrugs could be encapsulated within one cage. This host–guest complex, exhibiting a diameter of about 3 nm, has been characterized by detailed NMR spectroscopic measurements. Owing to the high positive charge, this nanostructure exhibits high cellular uptake. Upon entering cells and reacting with biological reductants such as ascorbic acid, the host–guest complex releases cisplatin, which leads to cell cycle arrest and apoptosis. The fully assembled complex displays cytotoxicity comparable to that of cisplatin against a panel of human cancer cell lines, whereas the cage or the Pt(iv) guest alone exhibit lower cytotoxicity. These findings indicate the potential of utilising well-defined supramolecular constructs for the delivery of prodrug molecules.     

Tuning the porosity of triangular supramolecular adsorbents for superior haloalkane isomer separations

Distillation-free separations of haloalkane isomers represents a persistent challenge for the chemical industry. Several classic molecular sorbents show high selectivity in the context of such separations; however, most suffer from limited tunability or poor stability. Herein, we report the results of a comparative study involving three trianglamine and trianglimine macrocycles as supramolecular adsorbents for the selective separation of halobutane isomers. Methylene-bridged trianglamine, TA, was found to capture preferentially 1-chlorobutane (1-CBU) from a mixture of 1-CBU and 2-chlorobutane (2-CBU) with a purity of 98.1%. It also separates 1-bromobutane (1-BBU) from a mixture of 1-BBU and 2-bromobutane (2-BBU) with a purity of 96.4%. The observed selectivity is ascribed to the thermodynamic stability of the TA-based host–guest complexes. Based on single crystal X-ray diffraction analyses, a [3]pseudorotaxane structure (2TA⊃1-CBU) is formed between TA and 1-CBU that is characterized by an increased level of noncovalent interactions compared to the corresponding [2]pseudorotaxane structure seen for TA⊃2-CBU. We believe that molecular sorbents that rely on specific molecular recognition events, such as the triangular pores detailed here, will prove useful as next generation sorbents in energy-efficient separations.

The methylene-bridged trianglamine (TA) can selectively capture 1-chlorobutane from a mixture of 1-chlorobutane and 2-chlorobutane due to the greater thermodynamic stability of the TA-based host–guest complex formed with 1-chlorobutane.