Broad-Spectrum Extracellular Antiviral Properties of Cucurbit[n]urils.

Viruses are microscopic pathogens capable of causing disease and are responsible for a range of human mortalities and morbidities worldwide. They can be rendered harmless or destroyed with a range of antiviral chemical compounds. Cucurbit[n]urils (CB[n]s) are a family of macrocycle chemical compounds existing as a range of homologues; due to their structure, they can bind to biological materials, acting as supramolecular "hosts" to "guests", such as amino acids. Due to the increasing need for a nontoxic antiviral compound, we investigated whether cucurbit[n]urils could act in an antiviral manner. We have found that certain cucurbit[n]uril homologues do indeed have an antiviral effect against a range of viruses, including herpes simplex virus 2 (HSV-2), respiratory syncytial virus (RSV) and SARS-CoV-2. In particular, we demonstrate that CB[7] is the active homologue of CB[n], having an antiviral effect against enveloped and nonenveloped species. High levels of efficacy were observed with 5 min contact times across different viruses. We also demonstrate that CB[7] acts with an extracellular virucidal mode of action via host-guest supramolecular interactions between viral surface proteins and the CB[n] cavity, rather than via cell internalization or a virustatic mechanism. This finding demonstrates that CB[7] acts as a supramolecular virucidal antiviral (a mechanism distinct from other current extracellular antivirals), demonstrating the potential of supramolecular interactions for future antiviral disinfectants.

Microcapsule Buckling Triggered by Compression-Induced Interfacial Phase Change.

There is an emerging trend toward the fabrication of microcapsules at liquid interfaces. In order to control the parameters of such capsules, the interfacial processes governing their formation must be understood. Here, poly(vinyl alcohol) films are assembled at the interface of water-in-oil microfluidic droplets. The polymer is cross-linked using cucurbit[8]uril ternary supramolecular complexes. It is shown that compression-induced phase change causes the onset of buckling in the interfacial film. On evaporative compression, the interfacial film both increases in density and thickens, until it reaches a critical density and a phase change occurs. We show that this increase in density can be simply related to the film Poisson ratio and area compression. This description captures fundamentals of many compressive interfacial phase changes and can also explain the observation of a fixed thickness-to-radius ratio at buckling, [Formula: see text].

Microfluidic Droplet-Facilitated Hierarchical Assembly for Dual Cargo Loading and Synergistic Delivery.

Bottom-up hierarchical assembly has emerged as an elaborate and energy-efficient strategy for the fabrication of smart materials. Herein, we present a hierarchical assembly process, whereby linear amphiphilic block copolymers are self-assembled into micelles, which in turn are accommodated at the interface of microfluidic droplets via cucurbit[8]uril-mediated host-guest chemistry to form supramolecular microcapsules. The monodisperse microcapsules can be used for simultaneous carriage of both organic (Nile Red) and aqueous-soluble (fluorescein isothiocyanate-dextran) cargo. Furthermore, the well-defined compartmentalized structure benefits from the dynamic nature of the supramolecular interaction and offers synergistic delivery of cargos with triggered release or through photocontrolled porosity. This demonstration of premeditated hierarchical assembly, where interactions from the molecular to microscale are designed, illustrates the power of this route toward accessing the next generation of functional materials and encapsulation strategies.

Electrostatically Directed Self-Assembly of Ultrathin Supramolecular Polymer Microcapsules.

Supramolecular self-assembly offers routes to challenging architectures on the molecular and macroscopic scale. Coupled with microfluidics it has been used to make microcapsules-where a 2D sheet is shaped in 3D, encapsulating the volume within. In this paper, a versatile methodology to direct the accumulation of capsule-forming components to the droplet interface using electrostatic interactions is described. In this approach, charged copolymers are selectively partitioned to the microdroplet interface by a complementary charged surfactant for subsequent supramolecular cross-linking via cucurbit[8]uril. This dynamic assembly process is employed to selectively form both hollow, ultrathin microcapsules and solid microparticles from a single solution. The ability to dictate the distribution of a mixture of charged copolymers within the microdroplet, as demonstrated by the single-step fabrication of distinct core-shell microcapsules, gives access to a new generation of innovative self-assembled constructs.

Supramolecular hydrogel microcapsules via cucurbit[8]uril host-guest interactions with triggered and UV-controlled molecular permeability.

Host-guest assembly in droplet-based microfluidics opens a new avenue for fabricating supramolecular hydrogel microcapsules with high monodispersity and controlled functionality. In this paper, we demonstrate a single emulsion microdroplet platform to prepare microcapsules with supramolecular hydrogel skins from host molecule cucurbit[8]uril and guest polymer anthracene-functionalized hydroxyethyl cellulose. In contrast to construction of microcapsules from a droplet-in-droplet double emulsion, here the electrostatic attraction between charged polymer and surfactant facilitates formation of defined supramolecular hydrogel skins in a single emulsion. Furthermore, by taking advantage of dynamic interactions and the tunable cross-linked supramolecular hydrogel network, it is possible to prepare microcapsules with triggered and UV-controlled molecular permeability. These could be potentially used in a delivery system for e.g. agrochemicals, nutraceuticals or cosmetics.

Efficient host-guest energy transfer in polycationic cyclophane-perylene diimide complexes in water.

We report the self-assembly of a series of highly charged supramolecular complexes in aqueous media composed of cyclobis(4,4'-(1,4-phenylene)bispyridine-p-phenylene)tetrakis(chloride) (ExBox) and three dicationic perylene diimides (PDIs). Efficient energy transfer (ET) is observed between the host and guests. Additionally, we show that our hexacationic complexes are capable of further complexation with neutral cucurbit[7]uril (CB[7]), producing a 3-polypseudorotaxane via the self-assembly of orthogonal recognition moieties. ExBox serves as the central ring, complexing to the PDI core, while two CB[7]s behave as supramolecular stoppers, binding to the two outer quaternary ammonium motifs. The formation of the 3-polypseudorotaxane results in far superior photophysical properties of the central PDI unit relative to the binary complexes at stoichiometric ratios. Lastly, we also demonstrate the ability of our binary complexes to act as a highly selective chemosensing ensemble for the neurotransmitter melatonin.

In situ SERS monitoring of photochemistry within a nanojunction reactor.

We demonstrate a powerful SERS-nanoreactor concept composed of self-assembled gold nanoparticles (AuNP) linked by the sub-nm macrocycle cucurbit[n]uril (CB[n]). The CB[n] functions simultaneously as a nanoscale reaction vessel, sequestering and templating a photoreaction within, and also as a powerful SERS-transducer through the large field enhancements generated within the nanojunctions that CB[n]s define. Through the enhanced Raman fingerprint, the real-time SERS-monitoring of a prototypical stilbene photoreaction is demonstrated. By choosing the appropriate CB[n] nanoreactor, selective photoisomerism or photodimerization is monitored in situ from within the AuNP-CB[n] nanogap.

Dynamically crosslinked materials via recognition of amino acids by cucurbit[8]uril.

Hydrogels, an increasingly important class of material, have physical properties amenable to many potential uses, particularly in the biomedical area. Utilisation of hydrogels, however, relies not only on their mechanical properties but also on a favourable toxicity profile. Self assembly of polymers through naturally occurring and non-toxic units is therefore a very attractive option. The aromatic amino acids phenylalanine and tryptophan are two such molecular units that form 2 : 1 complexes with cucurbit[8]uril (CB[8]) with high binding equilibrium constants (Keq up to 1012 M-2). Herein, water soluble styrenic monomers were copolymerised with synthetically derived aromatic amino acid monomers of phenylalanine and tryptophan. The resulting polymers were shown to form dynamic and self-healing physically crosslinked hydrogels via recognition and binding of the amino acids to cucurbit[8]uril.

One-step fabrication of supramolecular microcapsules from microfluidic droplets.

Although many techniques exist for preparing microcapsules, it is still challenging to fabricate them in an efficient and scalable process without compromising functionality and encapsulation efficiency. We demonstrated a simple one-step approach that exploits a versatile host-guest system and uses microfluidic droplets to generate porous microcapsules with easily customizable functionality. The capsules comprise a polymer-gold nanoparticle composite held together by cucurbit[8]uril ternary complexes. The dynamic yet highly stable micrometer-sized structures can be loaded in one step during capsule formation and are amenable to on-demand encapsulant release. The internal chemical environment can be probed with surface enhanced Raman spectroscopy.

Supramolecular gold nanoparticle-polymer composites formed in water with cucurbit[8]uril.

A gold nanoparticle-polymer composite material has been prepared in water using cucurbit[8]uril as a supramolecular "handcuff" to hold together viologen-functionalised gold nanoparticles and a naphthol-functionalised acrylamide copolymer.

Harnessing the energy of molecular recognition in a nanomachine having a photochemical on/off switch.

6A-Deoxy-6A-(N-methyl-3-phenylpropionamido)-beta-cyclodextrin operates as a molecular machine, where the amide group serves as a torsion bar to harness the work output resulting from extraction of 1-adamantanol and consequent complexation of the aryl substituent by the cyclodextrin, when the latter behave as the piston and cylinder, respectively, of a molecular pump. At 25 degrees C, the complexation changes the ratio of the amide (Z)- and (E)-isomers from 2.4:1 to 25:1, on which basis the work performed on the amide bond is calculated to be 1.4 kcal mol-1. trans-6A-Deoxy-6A-(N-methylcinnamido)-beta-cyclodextrin and the cis isomer function as a more advanced version of the machine, with the alkene moiety serving as a photochemical on/off switch. Irradiation at 300 nm converts the trans cinnamide to the cis isomer, while the reverse process occurs at 254 nm. With the cis isomer there is little interaction of the phenyl group with the cyclodextrin cavity, so in that mode the machine is turned off. By contrast, complexation of the aryl substituent by the cyclodextrin occurs with the trans cinnamide and changes the ratio of the amide (Z)- and (E)-isomers from 2.6:1 to 100:1. Consequently, in this mode the machine is turned on, and the work harnessed by the amide bond is 2.1 kcal mol-1.