Selenacrown Macrocycle in Aqueous Medium: Synthesis, Redox-Responsive Self-Assembly, and Enhanced Disulfide Formation Reaction.

Organic selenides are famous for their coordination and catalytic functions in the organic phase, albeit challenging for aqueous medium. Herein, the combination of a hydrophilic body of crown ether and substitution of one oxygen atom with a selenium one provides a new type of design route for organic selenide entities with charming functions in aqueous solution. The selenacrown ether C9Se presented here intrinsically shows an amphiphile-like property. Its nanosphere structure in water readily expands the catalysis of organic selenide to aqueous substrates in thiol/disulfide conversion.

Heterogeneous Metal-Organic-Framework-Based Biohybrid Catalysts for Cascade Reactions in Organic Solvent.

In cooperative catalysis, the combination of chemo- and biocatalysts to perform one-pot reactions is a powerful tool for the improvement of chemical synthesis. Herein, UiO-66-NH2 was employed to stepwise immobilize Pd nanoparticles (NPs) and Candida antarctica lipase B (CalB) for the fabrication of biohybrid catalysts for cascade reactions. Distinct from traditional materials, UiO-66-NH2 has a robust but tunable structure that can be utilized with a ligand exchange approach to adjust its hydrophobicity, resulting in excellent catalyst dispersity in diverse reaction media. These attractive properties contribute to the formation of MOF-based biohybrid catalysts with high activity and selectivity in the synthesis of benzyl hexanoate from benzaldehyde and ethyl hexanoate. With this proof-of-concept, we reasonably expect that future tailor-made MOFs can combine other catalysts, ranging from chemical to biological catalysts for applications in industry.

Biological Macrocycle: Supramolecular Hydrophobic Guest Transport System Based on Nanodiscs with Photodynamic Activity.

A biogenic macrocycle-based guest loading system has been developed by the self-assembly of membrane scaffold protein and phospholipids. The resulting 10 nm level transport system can increase the solubility of hydrophobic photodynamic agent hypocrellin B in aqueous medium and exhibited a cellular internalization capacity with substantial photodynamic activity.

Supramolecular Gel Based on Crown-Ether-Appended Dynamic Covalent Macrocycles.

A new type of dynamic covalent macrocycle with self-promoted supramolecular gelation behavior is developed. Under oxidative conditions, the dithiol compound containing a diamide alkyl linker with an odd number (7) of carbon chain and an appended crown ether shows a remarkable gelation ability in acetonitrile, without any template molecules. Due to the existence of crown ethers and disulfide bonds, the obtained gel shows a multiple stimuli-responsiveness behavior. The mechanical properties and reversibility of the gel are investigated. Computational modeling suggests that the peripheral chain for diamide hydrogen bonding is responsible for the gelation process.

Self-assembly behaviors of perylene- and naphthalene-crown macrocycle conjugates in aqueous medium.

The synthesis of conjugates of perylene diimide (PDI) and naphthalene diimide (NDI) modified with two benzo-21-crown-7 ethers (B21C7) are herein described. Their self-assembly behavior in various solvents was investigated particularly in aqueous medium, due to the recently discovered hydrophilic properties of B21C7 crown macrocycle. An unexpected fluorescence quenching phenomenon was observed in the PDI-B21C7 macrocycle conjugate in chloroform. The detailed UV-vis absorption and fluorescence spectra of these PDI/NDI derivatives in different solvents as well as their morphologies were investigated.

Ion Selectivity in Nonpolymeric Thermosensitive Systems Induced by Water-Attenuated Supramolecular Recognition.

The chemistry of aqueous salt solutions is rich with ambiguities, especially in stimuli-responsive supramolecular systems. Rational use of ion specificity to design supramolecular responsive materials, however, remains a challenging task. In this work, a low-molecular-weight supramolecular system was developed that was used to reveal the underlying systematic relationship between ions, water, and solutes. By utilizing these water-attenuated supramolecular forces (with Ka only ca. 30 m-1 ), an alternative concept for fabricating an aqueous responsive system in ionic medium was demonstrated. This work not only provides mechanistic insight into the underdeveloped role of topology in ion specificity upon noncharged polar surfaces, but also demonstrates the feasibility of utilizing weak supramolecular approaches to control the thermoresponsiveness.

Thermosensitive Phase Behavior of Benzo-21-crown-7 and Its Derivatives.

For designing water-soluble responsive materials, utilizing crown ethers as main building blocks has been rarely explored in contrast to their linear poly(ethylene glycol) counterparts. In the current study, we report the robust thermoresponsive properties of the benzo-21-crown-7 (B21C7) family with lower critical solution temperature (LCST) and upper critical solution temperature (UCST) behavior. Different substituent groups on the benzene ring exhibit significant effects on water solubility and thermoresponsiveness. B21C7 and its cyano derivative display LCST phenomena, while B21C7-based carboxylic acid derivative presents UCST followed by LCST phase behavior. Supramolecular interactions with KCl provide an additional tuning approach for this crown ether system. These results demonstrate that B21C7s can serve as an easily accessible toolbox to develop new thermosensitive systems and prepare thermally responsive materials.

Gas-phase chemistry of molecular containers.

The remarkable technical advances in mass spectrometry during the last decades, including soft ionisation techniques, the coupling of electrospray ionisation to flow reactors, and the broad scope of tandem mass spectrometric experiments applicable to mass-selected ions allow investigating the chemistry of molecular capsules in solution as well as in the absence of any environment. With these methods, mass spectrometry is capable of answering many questions starting from providing analytical characterisation data (elemental composition, stoichiometry, etc.) to structural aspects (connectivities, positions of building blocks in supramolecular complexes) and to the examination of solution and gas-phase reactivity including reactions inside molecular containers. The present article reviews this work with a focus rather on the chemical questions that can be answered than on the technical specialities of (tandem) mass spectrometry.

Multivalency at Interfaces: Supramolecular Carbohydrate-Functionalized Graphene Derivatives for Bacterial Capture, Release, and Disinfection.

A supramolecular carbohydrate-functionalized two-dimensional (2D) surface was designed and synthesized by decorating thermally reduced graphene sheets with multivalent sugar ligands. The formation of host-guest inclusions on the carbon surface provides a versatile strategy, not only to increase the intrinsic water solubility of graphene-based materials, but more importantly to let the desired biofunctional binding groups bind to the surface. Combining the vital recognition role of carbohydrates and the unique 2D large flexible surface area of the graphene sheets, the addition of multivalent sugar ligands makes the resulting carbon material an excellent platform for selectively wrapping and agglutinating Escherichia coli (E. coli). By taking advantage of the responsive property of supramolecular interactions, the captured bacteria can then be partially released by adding a competitive guest. Compared to previously reported scaffolds, the unique thermal IR-absorption properties of graphene derivatives provide a facile method to kill the captured bacteria by IR-laser irradiation of the captured graphene-sugar-E. coli complex.

Exploring macrocycles in functional supramolecular gels: from stimuli responsiveness to systems chemistry.

CONSPECTUS: Supramolecular gels are ideal candidates for soft, stimuli-responsive materials, because they combine the elastic behavior of solids with the microviscous properties of fluids. The dynamic networks of fibers in supramolecular gels are reminiscent of the cytoskeleton of a cell and provide scaffolds to implement function. When gels are made responsive to stimuli, these mechanical properties can be controlled. Gel-sol transitions also open opportunities to immobilize molecules inside the gel's cavities and to release them on demand. To establish selective responsiveness, suitable recognition sites are required influencing the properties of the fiber network depending on the presence of the stimulus. Supramolecular gels are expected to be stimuli-responsive per se, for example, to temperature, mechanical stress, or an environment that is competitive with the noncovalent interactions connecting the low-molecular weight gelators. Nevertheless, the opportunities for controlling the mechanical properties are rather limited, if one merely relies on interfering with these interactions. It would be much more promising to equip the gel with additional receptor sites that offer selectivity for a broader variety of chemical stimuli. Macrocycles often exhibit a distinct host-guest chemistry and thus are excellent candidates for this purpose. A broad variety of macrocycles differing with respect to structure, topology, solubility, or biocompatibility have been incorporated in gels and endow gels with responsiveness and function. Macrocycles can have different roles: They offer rather rigid scaffolds for the construction of structurally well-defined gelator molecules. Furthermore, their host-guest interactions can be integral to gel formation, if these interactions are required to build the gel fibers. Finally, macrocycles can also be functional groups with which gelators are equipped that would also form gels in the absence of the macrocycle. Here, the macrocycle can be used as a binding site to allow additional stimuli control. To combine different stimuli for triggering gel-sol transitions certainly expands the options for establishing stimuli responsiveness. If, for example, an agent trapped inside the gel is only liberated when two different stimuli are present simultaneously, its release can be controlled with much higher precision and selectivity compared with a gel that responds to one stimulus only. In this Account, the recent progress in the construction of functional macrocycle-containing supramolecular gels is summarized. First, recent strategies to engineer responsiveness into macrocycle-containing gels are discussed. Next, different functions are presented including applications as responsive reaction media, for controlled drug-delivery or tissue engineering, and as self-healing materials. Finally, we highlight the recent progress in designing macrocycle-containing supramolecular gel materials exhibiting complex behavior. This field is part of systems chemistry and still in its infancy but appears to be one of the most promising routes to smart responsive materials.

Self-recovering stimuli-responsive macrocycle-equipped supramolecular ionogels with unusual mechanical properties.

A chiral, crown-ether-functionalized bisurea gelator forms supramolecular gels in ionic liquids. The resulting ionogels show a remarkably high thermal stability with gel-sol transition temperatures (T(gs)) reaching more than 100 °C. The mechanical strength of these ionogels is surprisingly high and even comparable to that of cross-linked protein fibres. Furthermore, the ionogels exhibit rapid self-recovery properties after structural damage caused by deformation. Pseudorotaxanes form from the gelators' benzo[21]crown-7 ethers as the wheels and secondary ammonium ions as the axles despite the competition between that cation and the imidazolium ions of the ionic liquid for crown ether binding. Pseudorotaxane formation as an external chemical stimulus triggers the gel-sol transition of the ionogels.

A redox-responsive macrocycle based on the crown ether C7Te for enhanced bacterial inhibition.

Due to increasing bacterial resistance to disinfectants, there is an urgent need for new therapeutic agents and strategies to effectively inhibit bacteria. Accordingly, we have designed and synthesized a novel crown ether known as C7Te, and its oxidized form C7TeO. These compounds have demonstrated antibacterial effectiveness against Gram-negative E. coli (BL21). Notably, C7Te has the capability to enhance the inhibition of E. coli and the prevention of biofilm formation by H2O2 through a redox response. It can also effectively disrupt preformed E. coli biofilms by penetrating biofilm barriers effectively. Additionally, computer modeling of the bacterial cell membrane using nanodiscs composed of phospholipids and encircled amphipathic proteins with helical belts has revealed that C7Te can insert into and interact with phospholipids and proteins. This interaction results in the disruption of the bacterial cell membrane leading to bacterial cell death. The utilization of redox-responsive crown ethers to augment the antibacterial capabilities of H2O2-based disinfectants represents a novel approach to supramolecular bacterial inhibition.

Single-layer semiconductor-decorated flexible 2D protein nanosheets by engineered anchoring for efficient photocatalytic hydrogen production.

Protein self-assembly can be accurately manipulated to form ordered nanostructures through various supramolecular forces. This strategy is expected to make significant breakthroughs in the field of new biomimetic functional materials. Specifically, the construction of photocatalytic systems on two-dimensional (2D) flexible protein nanosheets meets a great challenge. We introduce a synthetic methodology for creating single-layer semiconductor-decorated protein 2D materials under mild conditions with enhanced light-driven hydrogen production. This approach employs a bioengineered green fluorescent protein (E4P) with the addition of a Cd-binding peptide, enabling precise control of the assembly of CdS quantum dots (QDs) on the protein's surface. Consequently, we obtained 4.3 nm-thin single-layer 2D protein nanosheets with substantial surface areas ideal for accommodating CdS QDs. By orthogonal incorporation of metal-binding peptides and supramolecular coordination, significantly enhancing the overall photocatalytic efficiency. Our findings demonstrate the potential for stable and efficient hydrogen production, highlighting the adaptability and biocompatibility of protein scaffolds for photocatalysis.

Liquid-Liquid Phase Separation-Mediated Photocatalytic Subcellular Hybrid System for Highly Efficient Hydrogen Production.

Plant chloroplasts have a highly compartmentalized interior, essential for executing photocatalytic functions. However, the construction of a photocatalytic reaction compartment similar to chloroplasts in inorganic-biological hybrid systems (IBS) has not been reported. Drawing inspiration from the compartmentalized chloroplast and the phenomenon of liquid-liquid phase separation, herein, a new strategy is first developed for constructing a photocatalytic subcellular hybrid system through liquid-liquid phase separation technology in living cells. Photosensitizers and in vivo expressed hydrogenases are designed to coassemble within the cell to create subcellular compartments for synergetic photocatalysis. This compartmentalization facilitates efficient electron transfer and light energy utilization, resulting in highly effective H2 production. The subcellular compartments hybrid system (HM/IBSCS) exhibits a nearly 87-fold increase in H2 production compared to the bare bacteria/hybrid system. Furthermore, the intracellular compartments of the photocatalytic reactor enhance the system's stability obviously, with the bacteria maintaining approximately 81% of their H2 production activity even after undergoing five cycles of photocatalytic hydrogen production. The research brings forward visionary prospects for the field of semi-artificial photosynthesis, offering new possibilities for advancements in areas such as renewable energy, biomanufacturing, and genetic engineering.

Multivalency in the gas phase: H/D exchange reactions unravel the dynamic "rock 'n' roll" motion in dendrimer-dendrimer complexes.

Noncovalent dendrimer-dendrimer complexes were successfully ionized by electrospray ionization of partly protonated amino-terminated polypropylene amine (POPAM) and POPAM dendrimers fully functionalized with benzo[21]crown-7 on all branches. Hydrogen/deuterium exchange (HDX) experiments conducted on dendrimer-dendrimer complexes in the high vacuum of a mass spectrometer give rise to a complete exchange of all labile NH hydrogen atoms. As crown ethers represent noncovalent protective groups against HDX reactions on the ammonium group to which they are coordinated, this result provides evidence for a very dynamic binding situation: each crown is mobile enough to move from one ammonium binding site to another. Schematically, one might compare this motion with two rock 'n' roll dancers that swirl around each other without completely losing all contact at any time. Although the multivalent attachment certainly increases the overall affinity, the "microdynamics" of individual site binding and dissociation remains fast.

Fibrous networks with incorporated macrocycles: a chiral stimuli-responsive supramolecular supergelator and its application to biocatalysis in organic media.

A new and versatile, crown ether appended, chiral supergelator has been designed and synthesized based on the bis-urea motif. The introduction of a stereogenic center improved its gelation ability significantly relative to its achiral analogue. This low-molecular-weight gelator forms supramolecular gels in a variety of organic solvents. It is sensitive to multiple chemical stimuli and the sol-gel phase transitions can be reversibly triggered by host-guest interactions. The gel can be used to trap enzymes and release them on demand by chemical stimuli. It stabilizes the microparticles in Pickering emulsions so that enzyme-catalyzed organic reactions can take place in the polar phase inside the microparticles, the organic reactants diffusing through the biphasic interface from the surrounding organic phase. Because of the higher interface area between the organic and polar phases, enzyme activity is enhanced in comparison with simple biphasic systems.

Pseudorotaxanes with self-sorted sequence and stereochemical orientation.

Partner preferences in pseudorotaxane formation were exploited to establish an integrative self-sorting system able to discriminate simultaneously at the sequence and stereochemical level (see picture). It was found that calix[6]arenes were threaded selectively with a preferred orientation onto bisammonium axles, even when the structural differences between the possible building blocks were small and located remote from the binding sites.

The aqueous supramolecular chemistry of crown ethers.

This mini-review summarizes the seminal exploration of aqueous supramolecular chemistry of crown ether macrocycles. In history, most research of crown ethers were focusing on their supramolecular chemistry in organic phase or in gas phase. In sharp contrast, the recent research evidently reveal that crown ethers are very suitable for studying abroad range of the properties and applications of water interactions, from: high water-solubility, control of Hofmeister series, "structural water", and supramolecular adhesives. Key studies revealing more details about the properties of water and aqueous solutions are highlighted.

The Mechanism of Inflammatory Factors and Soluble Vascular Cell Adhesion Molecule-1 Regulated by Nuclear Transcription Factor NF-κB in Unstable Angina Pectoris.

This work is aimed at exploring the mechanism of inflammatory factors and soluble vascular cell adhesion molecule-1 (sVCAM-1) regulated by nuclear transcription factor-κB (NF-κB) in unstable angina pectoris (UAP). 60 patients with unstable angina pectoris (UAP), 60 patients with stable angina pectoris (SAP), and some healthy people (controls) were selected and included. Peripheral venous blood (PVB) of all subjects was collected to detect blood routine. The enzyme-linked immunosorbent assay (ELISA) was adopted for detecting Visfatin, sVCAM-1, soluble intervascular cell adhesion molecule-1 (sICAM-1), and inflammatory factors; flow cytometry (FCM) was to detect the CD63 and CD62P; real-time fluorescence quantitative polymerase chain reaction (rt-qPCR) was employed to detect the NF-κB1, NF-κB2, and REL mRNA. The hs-CRP results of UAP group, SAP group, and control group were 11.12 ± 1.5 mg/L, 10.23 ± 1.3 mg/L, and 4.51 ± 1.1 mg/L, respectively. The CD62P results of UAP group, SAP group, and control group were 16.07 ± 2.5%, 11.09 ± 1.8%, and 22.15 ± 0.4%, respectively. The high-sensitivity C-reactive protein (hs-CRP), inflammatory factors (IL-6, IL-17, IL-23, IL-1ß, and tumor necrosis factor α (TNF-α)), CD63, CD62P, NF-κB1, NF-κB2, and REL mRNA were obviously higher in the SAP group compared than the indicator values in the control group (P < 0.05). The relative REL expression results of UAP group, SAP group, and control group were 3.77 ± 1.5, 2.2 ± 0.6, and 1 ± 0.4, respectively. The inflammatory factors, Visfatin, sVCAM-1, sICAM-1, CD63, CD62P, NF-κB1, NF-κB2, and REL mRNA in the UAP group showed higher levels in contrast to the other two groups (P < 0.05). In summary, UAP patients had marked activation of the IL-23/IL-17 inflammatory axis, high expressions of sVCAM-1 and sICAM-1, and activation of the NF-κB pathway. Increase of inflammatory factors and sVCAM-1 regulated by NF-κB was closely correlated with UAP.

Assembly of Protein Cages for Drug Delivery.

Nanoparticles (NPs) have been widely used as target delivery vehicles for therapeutic goods; however, compared with inorganic and organic nanomaterials, protein nanomaterials have better biocompatibility and can self-assemble into highly ordered cage-like structures, which are more favorable for applications in targeted drug delivery. In this review, we concentrate on the typical protein cage nanoparticles drugs encapsulation processes, such as drug fusion expression, diffusion, electrostatic contact, covalent binding, and protein cage disassembly/recombination. The usage of protein cage nanoparticles in biomedicine is also briefly discussed. These materials can be utilized to transport small molecules, peptides, siRNA, and other medications for anti-tumor, contrast, etc.