Macrocyclic Cavity Research Articles

Supramolecular Guest Exchange in Cucurbit[7]uril for Bioorthogonal Fluorogenic Imaging across the Visible Spectrum.

Fluorogenic probes that unmask fluorescence signals in response to bioorthogonal reactions are a powerful new addition to biological imaging. They can significantly reduce background fluorescence and minimize nonspecific signals, potentially enabling real-time, high-contrast imaging without the need to wash out excess fluorophores. While diverse classes of highly refined synthetic fluorophores are now readily available, integrating them into a bioorthogonal fluorogenic scheme still requires extensive design efforts and customized structural alterations to optimize quenching mechanisms for each specific fluorophore scaffold. Herein, we present a highly generalizable strategy that can produce an efficient bioorthogonal fluorogenic response from essentially any readily available fluorophore without further structural alterations. We designed this strategy based on the macrocyclic cucurbit[7]uril (CB7) host, where a fluorogenic response is achieved by programming a guest exchange reaction within the macrocyclic cavity. We employed this strategy to rapidly create fluorogenic probes across the visible spectrum from diverse fluorophore scaffolds, which enabled no-wash imaging in live cells and tissues with minimal background signal. Finally, we demonstrated that this strategy can be combined with metabolic labeling for fluorogenic detection of metabolically tagged mycobacteria under no-wash conditions and paired with covalently clickable probes for high-contrast super-resolution and multiplexed imaging in cells and tissues.

Latent porosity of planar tris(phenylisoxazolyl)benzene.

Interest in developing separation systems for chemical entities based on crystalline molecules has provided momentum for the fabrication of synthetic porous materials showing selectivity in molecular encapsulation, such as metal-organic frameworks, covalent organic frameworks, hydrogen-bonded organic frameworks, zeolites, and macrocyclic molecular crystals. Among these, macrocyclic molecular crystals have generated renewed interest for use in separation systems. Selective encapsulation relies on the sizes, shapes, and dimensions of the pores present in the macrocyclic cavities; thus, nonmacrocyclic molecular crystals with high selectivity for molecular encapsulation via porosity-without-pore behaviors have not been studied. Here, we report that planar tris(phenylisoxazolyl)benzene forms porous molecular crystals possessing latent pores exhibiting porosity-without-pore behavior. After exposing the crystals to complementary guest molecules, the latent pores encapsulate cis- and trans-decalin while maintaining the structural rigidity responsible for the high selectivity. The encapsulation via porosity without pores is a kinetic process with remarkable selectivity for cis-decalin over trans-decalin with a cis-/trans-ratio of 96:4, which is confirmed by single-crystal X-ray diffraction and powder X-ray diffraction analyses. Hirshfeld surface analysis and fingerprint plots show that the latent intermolecular pores are rigidified by intermolecular dipole‒dipole and π-π stacking interactions, which determines the remarkable selectivity of molecular recognition.

Revealing the Unusual behavior of rhenium (I) tricarbonyl complex functionalized with Aza-Macrocycles in response to metal ions

Three new rhenium phenanthroline tricarbonyl complexes were synthesized and fully characterized to examine changes in their photophysical properties and spectroscopic behavior in the presence of metal ions. To achieve this, the complexes were designed with modifications in both the phenanthroline and the axial ligand. The 4,7–dichloro–1,10–phenanthroline (Cl2phen) precursor was functionalized with two units of 1–aza–15–crown–5 (1A15C5) to obtain the complex [Re((A15C5)2phen)(CO)3Br] (1) with the aim to study the spectroscopic perturbations induced by the binding of the metal ions by this receptor. Interestingly, the rhenium complex 1 shows a particular behavior towards Hg(II) and Pb(II), as a result of the halide abstraction assisted by these metal ions. Additionally, in the presence of Cu(II) the interaction and coordination/binding with the macrocycle cavities is also presumed. The chemical reaction assisted by Hg(II) was confirmed by changes in the absorption, emission and FT–IR spectra of [Re(Cl2phen)(CO)3Br] (2) in presence of the heavy metal ion. These obtained profiles had similar patterns to the ones shown by the cationic complex [Re(Cl2phen)(CO)3(CH3CN)]PF6 (3). As final confirmation, this last complex was also studied in the presence of metal ions and its spectra remained unaltered.

Unraveling Anomalies in Preferential Liquid Transport through the Intrinsic Pores of Cyclodextrin in Polyester Nanofilms.

The precise manipulation of the porous structure of the nanofiltration membrane is critical for unlocking enhanced separation efficiencies across various liquids and solutes. Ultrathin films of crosslinked macrocycles, specifically cyclodextrins (CDs), have drawn considerable attention in this area owing to their ability to facilitate precise molecular separation with high liquid permeance for both polar and non-polar liquids, resembling Janus membranes. However, the functional role of the intrinsic cavity of CD in liquid transport remains inadequately understood, demanding immediate attention in designing nanofiltration membranes. Here, the synthesis of polyester nanofilms derived from crosslinked β-CD, demonstrating remarkable Na2SO4 rejection (≈92 - 99.5%), high water permeance (≈4.4 - 37.4 Lm-2h-1bar-1), extremely low hexane permeance (<1 Lm-2h-1bar-1), and extremely high ratio (α > 500) of permeances for polar and non-polar liquids, is reported. Molecular simulations support the findings, indicating that neither the polar nor the non-polar liquids flow through the β-CD cavity in the nanofilm. Instead, liquid transport predominantly occurs through the 2.2nm hydrophilic aggregate pores. This challenges the presumed functional role of macrocyclic cavities in liquid transport and raises questions about the existence of the Janus structure in nanofiltration membranes produced from the macrocyclic monomers.

Nonpreferential Solvent Transport through an Intrinsic Cyclodextrin Pore in a Polyester Film.

We performed equilibrium molecular dynamics simulations to study the transport of water and hexane solvents through cyclodextrin(CD)-based membranes (α-/β-/γ-CD/TMC). Although it is known that water and hexane can permeate through the macrocyclic cavity, surprisingly, when it is present in the CD-based membrane (α-/β-/γ-CD/TMC), these solvents are not permeating through the CD cavity. Interactions between membrane functional group atoms with the water and hexane suggest that these solvents primarily permeate through the polar aggregate pores formed via ester-linkage rather than the CD cavity. Our observation reveals that both solvents can permeate through the membrane; however, the hexane flux was one order of magnitude lower than water flux. Our study suggests that further work is needed to confirm the functional significance of the macrocyclic cavity in solvent permeation and the existence of Janus pathways.

Mixed matrix membrane for hydrogen separation enhanced by Oxacalix[4]arene-Containing porous organic polymers

The mixed matrix membranes (MMMs) have great potential for industrial H2 enhancement applications. However, some challenges remain to incorporate the nanoporous architectures with industrial processable polymers. In this work, a macrocyclic cavitand from oxacalix[4]arene was integrated into porous polymers via a facile ring-opening-metathesis polymerization (ROMP), the resulting BIT-POP-20 was added to polysulfone matrix to make novel MMMs with different mass ratios. These membranes improved gas permeation rate for CO2, H2 and He, compared with pristine polysulfone, and high H2/N2 selectivity of 105 was achieved. This huge improved H2/N2 separation performances were due to the nanoporous gas passages through the open supramolecular cavities. This work presents an interesting example in designing MMMs using intrinsic macrocyclic cavity in porous polymer backbone that helps increase their performances in gas separations.

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This paper presents a novel macrocycle based on conformation‐adaptive and electron‐rich dihydrophenazine. The macrocycle exhibits host‐guest interaction with tetracyanoquinodimethane (TCNQ) driving by charge transfer interaction between them. The host‐guest complex forms stable radical cation species upon oxidation, resulting in the release of TCNQ from the macrocyclic cavity, thereby successfully achieving the reversible binding of guest molecules. More details are discussed in the article by Yang et al. on page 1895—1900.image

Selenoureido Calix[6]arenes: A Novel Platform for Pseudorotaxane Synthesis

AbstractHeteroditopic calix[6]arenes are widely employed macrocycles for the synthesis of pseudo‐oriented interlocked systems and stimuli‐induced molecular machines, among others. Herein, we introduce a new calix[6]arene receptor functionalised with three phenylselenoureido groups. These hydrogen‐bonding donor moieties are able to promote the threading of viologen‐based organic axles inside the macrocyclic cavity to form a stable pseudorotaxane species. Preliminary investigations using 1H‐NMR measurements and semi‐empirical and DFT studies suggested its further use as a platform for the synthesis of rotaxanes.

Adaptive tetralactam macrocycle based polymers for efficient and rapid removal of organic micropollutants with wide scope

With the rapid urbanization and industrialization of human society, water pollution issues caused by the increasing types and quantities of organic micropollutants have become increasingly severe. It is very urgent but also challenging to develop the rapid and efficient method for water purification with a wide removal scope. Herein, a cross-linked polymer adsorbent was fabricated by adaptive tetralactam macrocycle for rapid and efficient removal of multiple types of organic micropollutants in water, including dyes, pharmaceuticals, pesticides, and hormones. The removal efficiencies for the 20 tested organic micropollutants with diverse structures, sizes, and charges are all larger than 95.9 % and approaching 99.9 %, and most of the adsorption processes were finished within 5 min. The well-preorganized and adaptive cavity of tetralactam macrocycle endows the polymer adsorbent with excellent adsorption performance even in extreme conditions. Moreover, the tetralactam macrocycle-crosslinked polymer adsorbent could be regenerated easily and the performance was maintained after 6 cycles. It is demonstrated that the as-developed polymer has great potential in the removal of various hazardous organic pollutants in water.

Cyclic Azahelicene Dimers Showing Bright Circularly Polarized Luminescence and Selective Fluoride Recognition.

Although helicenes are promising molecules, the synthetic difficulty and tediousness have often been problems, and only small amounts of optically pure helicenes have been obtained by using chiral HPLC in most cases. Herein, aza[7]helicenes or closed-aza[7]helicenes with (1R)-menthyl substituents were selectively synthesized via the intramolecular Scholl reaction, and the diastereomeric pairs were separated by silica gel column chromatography. The optically pure helicenes were further transformed into the corresponding cyclic dimers, and the chiroptical properties were investigated. The rigid π-frameworks of the dimers led to the high molar extinction coefficients and fluorescence quantum yields, while the twisted helicene moieties induced clear Cotton effects and CPL in the visible region, and the high CPL brightness (BCPL) was achieved. Furthermore, the cyclic dimers were found to have the macrocyclic cavity with the two NH groups suitable for the selective binding of a fluoride anion, which induced significantly redshifted fluorescence and CPL in the red region.

Cyclic Azahelicene Dimers Showing Bright Circularly Polarized Luminescence and Selective Fluoride Recognition

AbstractAlthough helicenes are promising molecules, the synthetic difficulty and tediousness have often been problems, and only small amounts of optically pure helicenes have been obtained by using chiral HPLC in most cases. Herein, aza[7]helicenes or closed‐aza[7]helicenes with (1R)‐menthyl substituents were selectively synthesized via the intramolecular Scholl reaction, and the diastereomeric pairs were separated by silica gel column chromatography. The optically pure helicenes were further transformed into the corresponding cyclic dimers, and the chiroptical properties were investigated. The rigid π‐frameworks of the dimers led to the high molar extinction coefficients and fluorescence quantum yields, while the twisted helicene moieties induced clear Cotton effects and CPL in the visible region, and the high CPL brightness (BCPL) was achieved. Furthermore, the cyclic dimers were found to have the macrocyclic cavity with the two NH groups suitable for the selective binding of a fluoride anion, which induced significantly redshifted fluorescence and CPL in the red region.

Kinetics and thermodynamics of β-cyclodextrin-NH2/β-carotene complexation: how much energy is required to include a hydrophobic group in the macrocycle cavity?

Kinetics and thermodynamics of β-cyclodextrin-NH2/β-carotene complexation: how much energy is required to include a hydrophobic group in the macrocycle cavity?

The strategy of micropore confinement via organic macrocyclic cavities for designing novel high-performance proton exchange membranes

The high-temperature hydrogen proton exchange membrane fuel cell is considered a disruptive technology for future energy applications. However, the weak binding strength between the proton carriers (phosphoric acid molecules) with polymer chains reduces the operational stability and proton transfer efficiency at conditions of high temperature and low humidity. In this work, a strategy of micropore confinement via organic macrocyclic cavities (sulfonic calix[4]arenes, sulfonic calix[8]arenes, sulfonated β-cyclodextrin) was developed for designing novel mixed matrix membranes functioning as high-temperature hydrogen proton exchange membranes. Benefitting from the confined micropores constructed by supramolecular cavities, the obtained mixed matrix membranes showed a higher uptake and retention capability of phosphoric acid as well as lower membrane swelling, yielding an enhanced proton conductivity. The proton conductivity of the mixed matrix membranes was 2–3 times higher while the conductivity attenuation was only 58.6% comparing with neat PBI membrane, (140℃, relative humidity = 0). In addition, due to the good compatibility caused by hydrogen bonding between fillers and polymer chains, the volume swelling was only 14% and the mechanical strength of the obtained mixed matrix membranes increased. We believe the strategy of micropore confinement via organic macrocyclic cavities for designing the novel mixed matrix membranes is thought to be of great significance for the research on high-temperature proton exchange membrane.

DFT and TD DFT study of oxodiboron(III) phthalocyanine and peculiarities of spectral behavior and acid–base properties of its tert-butyl substituted derivative in solutions

Molecular and electronic structures of transoid and cisoid forms of oxodi(fluoroboron(III)) complex of phthalocyanine [O(FB)2Pc] in the ground and excited states were studied using DFT and TD DFT methods. The peculiarities of the electrochemical and spectral properties of the tetra-tert-butyl substituted complex existing in the transoid form in organic solvents and in acid medium were considered in comparison with 1:1 complexes formed by aluminum subgroup metals and boron(III) subphthalocyanine. Coordination of two boron atoms in the coordination cavity of the phthalocyanine macrocycle leads to its tetragonal distortion both in the cisoid and especially in the transoid forms and stabilizes the frontier π-molecular orbitals, especially the lowest unoccupied MO. This results in the bathochromic shift of the long-wave Q band and strongly facilitates the reduction of macrocycle occurring for the transoid form at −0.19 V versus Ag/AgCl in dimethylformamide (DMF). Spectrophotometric titration in CH2Cl2-CF3COOH medium showed that the basicity of the meso-nitrogens is decreased upon coordination of two boron atoms. Slow deborylation can occur either in a strongly acid medium (96% H2SO4) or in the presence of water in DMF. The absence of fluorescence and ability to generate singlet oxygen is explained by quenching of the excited state due to conformation flexibility of the macrocycle and inversion of the coordination center in the transoid form.

Peptidomimetics based on pillar[5]arene: Charge effect on self-assembly, toxicity, and herbicide binding

Contact herbicides are widely used if rapid weeds eradication is required despite of a number of inherent disadvantages (transfer to water and soil, damage of non-target plants, promotion of resistant weeds expansion, etc.). Supramolecular chemistry can solve the problems associated with herbicide degradation and spreading, as well as suppress their harmful effects on humans and the environment. Pillar[n]arene derivatives are of special interest among other macrocyclic platforms due to their ability to implement various substrates in the macrocycle cavity. However, most of the works devoted to the interaction of pillararenes with pesticides considers binding of paraquat and its derivatives. In this work, water soluble derivatives of pillar[5]arene containing L-tryptophan residues have been proposed for binding a range of herbicides including paraquat dichloride, pyridate, 3-(methylphosphinico)propionic acid, and glufosinate-ammonium. The ester derivative of pillar[5]arene was found to be able to bind the above species. The betaine derivative showed selective and efficient interaction with pyridate (logKa = 4.02) and paraquat (logKa = 3.17). The effect of the charge of the pillar[5]arene substituent on the toxicity of the macrocyclic platform towards A549 and LEK cell lines was demonstrated. Introduction of carboxylate functions to form betaine fragments compensated for the positive charge of the macrocycle substituent and decreased its toxicity by three orders of magnitude for A549 cell line (167.0 μM), and by two orders of magnitude for LEK cells (56.0 μM) compared to ester derivative of pillar[5]arene (3.1 and 3.6 μM respectively). The results obtained confirmed the prospects of the use of amino acid derivatized pillar[5]arenes in the development of new approaches to the removal of the herbicides from the environment that are demanded both in agriculture and aquaculture.

Precision ion separation via self-assembled channels

Selective nanofiltration membranes with accurate molecular sieving offer a solution to recover rare metals and other valuable elements from brines. However, the development of membranes with precise sub-nanometer pores is challenging. Here, we report a scalable approach for membrane fabrication in which functionalized macrocycles are seamlessly oriented via supramolecular interactions during the interfacial polycondensation on a polyacrylonitrile support layer. The rational incorporation of macrocycles enables the formation of nanofilms with self-assembled channels holding precise molecular sieving capabilities and a threshold of 6.6 ångström, which corresponds to the macrocycle cavity size. The resulting membranes provide a 100-fold increase in selectivity for Li+/Mg2+ separation, outperforming commercially available and state-of-the-art nanocomposite membranes for lithium recovery. Their performance is further assessed in high-recovery tests under realistic nanofiltration conditions using simulated brines or concentrated seawater with various Li+ levels and demonstrates their remarkable potential in ion separation and Li+ recovery applications.

Curcubit[8]uril-modulated asymmetric electroreductive hydrodimerization of coumarins with supramolecular encapsulation

The development of electrocatalytic methods for stereoselective reductive functionalization remains a challenge in organic synthesis. Herein, a novel strategy of supramolecule-modulated electrocatalytic stereoselectivity within the macrocyclic cavity is developed using a hybrid electrode prepared from the layer-by-layer assembly of Cu nanoparticles (CuNPs) and curcubit[8]uril (Q[8]). The hydrodimers with good yields of 71%-83% and superior stereoselectivity of up to 96% were afforded. The results of theoretical calculation and control experiments demonstrate that the hydrophobic cavity of Q[8] provides a microenvironment to accommodate two coumarin molecules via host–guest interactions. Q[8] plays a crucial role in modulating product stereoselectivity by controlling the assembly direction of coumarin toward “Head to Head” mode. The designed CuNPs-Q[8] electrode is remarkably stable, which can be reused five times at least without obvious loss of electrocatalytic activity.

Deciphering the mechanism of γ-cyclodextrin's hydrophobic cavity hydration: an integrated experimental and theoretical study.

Cyclodextrins (CDs) are host systems with inherent capability for inclusion complex formation with various molecular entities, mostly hydrophobic substances. Host CDs are highly accommodative to water molecules as well and usually contain water in the native state. There is still an ongoing discussion on both the total number of water molecules and their preferred binding position inside the cavities of the CDs. To understand the hydration/dehydration properties of γ-CD (the largest of the three most abundant native CDs), the main experimental methods applied in this study were differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). By coupling these techniques with density functional theory (DFT) calculations we try to shed some light on the mechanism of the γ-CD hydration and to address some unanswered questions: (i) what are the preferable locations for water molecules in the macrocyclic cavity ("hot spots"); (ii) what are the major factors contributing to the stability of the water cluster in the CD interior; (iii) what type of interactions (i.e., water-water and/or water-CD walls) contribute to the stability of the water assemble; (iv) how does the mechanism of the γ-CD hydration compare with those of its α-CD and β-CD counterparts.

Exo- or endo-1H-pyrazole metal coordination modulated by the polyamine chain length in [1 + 1] condensation azamacrocycles. Binuclear complexes with remarkable SOD activity.

The Cu2+ complexes of three [1 + 1] azacyclophane macrocycles having the 1H-pyrazole ring as the spacer and the pentaamine 1,5,8,11,15-pentaazadecane (L1) or hexaamines 1,5,8,12,15,19-hexaazanonadecane (L2) and 1,5,9,13,17,21-hexaazaheneicosane (L3) as bridges show endo- coordination of the pyrazolate bridge giving rise to discrete monomeric species. Previously reported pyrazolacyclophanes evidenced, however, exo-coordination with the formation of dimeric species of 2 : 2, 3 : 2 or even 4 : 2 Cu2+ : L stoichiometry. The complexes have been characterized in solution using potentiometric studies, UV-Vis spectroscopy, paramagnetic NMR, cyclic voltammetry and mass spectrometry. The measurements show that all three ligands have as many protonation steps in water as secondary amines are in the bridge, while they are able to form both mono- and binuclear Cu2+ species. The crystal structures of the complexes [Cu(HL1)Br]Br(1+x)(ClO4)(1-x)·yH2O (1) and [Cu2(H-1L2)Cl(ClO4)](ClO4)·H2O·C2H5OH (2) have been solved by X-ray diffraction studies. In 1 the metal ion lies at one side of the macrocyclic cavity being coordinated by one nitrogen of the pyrazolate moiety and the three consecutive nitrogen atoms of the polyamine bridge. The other nitrogen of the pyrazole ring is hydrogen-bonded to an amine group. In 2 the two metal ions are interconnected by a pyrazolate bis(monodentate) moiety and complete their coordination spheres with three amines and either a bromide or a perchlorate anion, which occupy the axial positions of distorted square pyramid geometries. Paramagnetic NMR studies of the binuclear complexes confirm the coordination pattern observed in the crystal structures. Cyclic voltamperommetry data show potentials within the adequate range to exhibit superoxide dismutase (SOD) activity. The IC50 values calculated by McCord-Fridovich enzymatic assays show that the binuclear Cu2+ complexes of L2 and L3 have SOD activities that rank amongst the highest ones reported so far.

Towards nanomaterials with tubular pores: synthesis and self-assembly of bis-pillar[5]arene

Recently, materials obtained using supramolecular chemistry approaches, and, in particular, spatially preorganized macrocyclic compounds, have attracted close attention of the researchers. Pillar[n]arenes are of special interest due to their tubular spatial structure and macrocyclic cavity. A similar tubular structure is retained in the supramolecular packaging of pillar[5]arene crystals, forming pores. In this study, we developed a block synthetic approach for the preparation of bis-pillar[5]arene containing amide groups. The ability of the synthesized bis-pillar[5]arene to form stable self-associates in solvents of different polarity (CHCl3 and CH3OH) was demonstrated by the DLS method. In trichloromethane at concentration of 1·10–3 M, monodisperse associates with average hydrodynamic diameter of 227 nm (PDI = 0.28) are formed; in methanol, stable associates (1·10–6 M) have an average hydrodynamic diameter of 136 nm (PDI = 0.21). The results obtained can be used to create new supramolecular systems, molecular machines, or capture and detect various organic molecules.