Jesús del Barrio

Photocontrol over Cucurbit[8]uril Complexes: Stoichiometry and Supramolecular Polymers

Herein we report the photocontrol of cucurbit[8]uril (CB[8])-mediated supramolecular polymerization of azobenzene-containing monomers. The CB[8] polymers were characterized both in solution and in the solid state. These host-guest complexes can be reversibly switched between highly thermostable photostationary states. Moreover, a remarkable stabilization of Z-azobenzene was achieved by CB[8] complexation, allowing for structural characterization in the solid state.

Triply Triggered Doxorubicin Release From Supramolecular Nanocontainers

The synthesis of a supramolecular double hydrophilic block copolymer (DHBC) held together by cucurbit[8]uril (CB[8]) ternary complexation and its subsequent self-assembly into micelles is described. This system is responsive to multiple external triggers including temperature, pH and the addition of a competitive guest. The supramolecular block copolymer assembly consists of poly(N-isopropylacrylamide) (PNIPAAm) as a thermoresponsive block and poly(dimethylaminoethylmethacrylate) (PDMAEMA) as a pH-responsive block. Moreover, encapsulation and controlled drug release was demonstrated with this system using the chemotherapeutic drug doxorubicin (DOX). This triple stimuli-responsive DHBC micelle system represents an evolution over conventional double stimuli-responsive covalent diblock copolymer systems and displayed a significant reduction in the viability of HeLa cells upon triggered release of DOX from the supramolecular micellar nanocontainers.

Formation of Single‐Chain Polymer Nanoparticles in Water through Host–Guest Interactions

The dynamic three-dimensional structures of enzymes are dictated by secondary bonding interactions and play a crucial role in both molecular recognition and allosteric regulation. Controlled crosslinking of single polymer chains in isolation, that can be seen as a mimic of the self-organization of enzymes, has previously been realized in organic solvents through crosslinking of multivalent polymer chains under highly dilute conditions. 2] In this instance, crosslinking must be specifically intramolecular to form these “self-collapsed” single-chain polymeric entities, which have been reported as discrete, spherical nanoparticulate structures. Whilst a few of the above systems are documented in the literature, where novel applications for such systems have been realized, only a small number are shown to be reversible and only one example exists in water. Moreover, the controlled folding and unfolding of a single polymer chain in water has not yet been realized. A completely reversible form of this system would be beneficial for many reasons, especially in light of one notable property of these nanoparticles (NPs), which is their ability to produce non-Einsteinian reductions in viscosity. Supramolecular crosslinking motifs exploit well-established non-covalent interactions and their incorporation into molecular constructs has led to the formation of materials with novel properties. Notable examples of such materials predominantly include gelating entities where intermolecular crosslinking leads to gel formation. This strategy has been particularly successful for systems that consist of polymeric subunits which are able to gel through multivalent functionality. Cucurbit[8]uril (CB[8]), a macrocylic host molecule capable of binding two aromatic guest molecules simultaneously, is a suitable candidate for such reversible crosslinking on account of the variety of guests available for binding. This allows for the use of guests with a range of orthogonal stimuli where guest binding can be controlled through simple external conditions (e.g. temperature, pH, light, competing guests), thus allowing for reversibility to be easily achieved. As a result, a variety of systems have already been produced bearing this reversible CB[8]-based crosslinking motif. Herein we document a CB[8]-mediated system for the preparation of metastable single-chain polymer nanoparticles. These nanoparticles are shown to form rapidly, are highly tunable and reversible and do not require protection chemistries (Figure 1).

Triggered insulin release studies of triply responsive supramolecular micelles

The synthesis of a supramolecular double hydrophilic glucose responsive block copolymer (DHBC) held together by cucurbit[8]uril (CB[8]) ternary complexation and its subsequent self-assembly into micelles is described. The supramolecular block copolymer assembly consists of poly(N-isopropylacrylamide) (PNIPAAm) and poly(acrylamidophenyl boronic acid) (PAAPBA) as temperature and glucose responsive blocks, respectively, and poly(dimethylacrylamide) (PDMAAm) as a hydrophilic block. Drug release studies of insulin-loaded micelles using three external triggers were studied with release of insulin achieved by changing temperature, glucose concentration or by adding a competitive guest for CB[8]. This system offers good control over the release of insulin under physiological conditions (pH 7.4, 37 °C). These exciting results suggest that this system could be a model for a clinically relevant drug delivery vehicle for diabetic treatment.

Supramolecular polymeric peptide amphiphile vesicles for the encapsulation of basic fibroblast growth factor

The synthesis of a supramolecular double hydrophilic peptide-conjugated polymer held together by cucurbit[8]uril (CB[8]) ternary complexation and its subsequent temperature triggered self-assembly into vesicles are described. Basic fibroblast growth factor can be easily loaded into the vesicles under benign conditions and their bioactivities can be preserved without the need for excipients such as heparin.

Temperature‐ and Voltage‐Induced Ligand Rearrangement of a Dynamic Electroluminescent Metallopolymer

A dynamic-covalent metal-containing polymer was synthesized by the condensation of linear diamine and dialdehyde subcomponents around copper(I) templates in the presence of bidentate phosphine ligands. In solution, the red polymers undergo a sol-gel transition upon heating to form a yellow gel, a process that can be either reversible or irreversible depending on the solvent used. When fabricated into a light-emitting electrochemical cell (LEC), the polymer emits infrared light at low voltage. As the voltage is increased, a blue shift in the emission wavelength is observed until yellow light is emitted, a process which is gradually reversed over time upon lowering the voltage. The mechanism underlying these apparently disparate responses is deduced to be due to loss of the copper phosphine complex from the polymer.

Metastable single-chain polymer nanoparticles prepared by dynamic cross-linking with nor-seco-cucurbit[10]uril

We present the preparation of metastable single-chain polymeric nanoparticles through stimuli-responsive and reversible intramolecular cross-linking of a single polymer chain in water. Functionalisation of poly(N-hydroxyethylacrylamide) polymers with viologen, followed by addition of nor-seco-cucurbit[10]uril allows for facile preparation of nanoparticles through specific and tightly binding 2 : 1 homo-ternary complexes. Particle sizes can be readily tuned through either polymer molecular weight or degree of cross-linking. By virtue of the supramolecular nature of the intramolecular cross-linking in water, the formation of these metastable nanoparticles represents a step towards the development of synthetic polymers with aqueous phase behaviour analogous to the self folding of biomacromolecules.

The Importance of Excess Poly(N-isopropylacrylamide) for the Aggregation of Poly(N-isopropylacrylamide)-Coated Gold Nanoparticles

Thermoresponsive materials are generating significant interest on account of the sharp and tunable temperature deswelling transition of the polymer chain. Such materials have shown promise in drug delivery devices, sensing systems, and self-assembly. Incorporation of nanoparticles (NPs), typically through covalent attachment of the polymer chains to the NP surface, can add additional functionality and tunability to such hybrid materials. The versatility of these thermoresponsive polymer/nanoparticle materials has been shown previously; however, significant and important differences exist in the published literature between virtually identical materials. Here we use poly(N-isopropylacrylamide) (PNIPAm)-AuNPs as a model system to understand the aggregation behavior of thermoresponsive polymer-coated nanoparticles in pure water, made by either grafting-to or grafting-from methods. We show that, contrary to popular belief, the aggregation of PNIPAm-coated AuNPs, and likely other such materials, relies on the size and concentration of unbound “free” PNIPAm in solution. It is this unbound polymer that also leads to an increase in solution turbidity, a characteristic that is typically used to prove nanoparticle aggregation. The size of PNIPAm used to coat the AuNPs, as well as the concentration of the resultant polymer–AuNP composites, is shown to have little effect on aggregation. Without free PNIPAm, contraction of the polymer corona in response to increasing temperature is observed, instead of nanoparticle aggregation, and is accompanied by no change in solution turbidity or color. We develop an alternative method for removing all traces of excess free polymer and develop an approach for analyzing the aggregation behavior of such materials, which truly allows for heat-triggered aggregation to be studied.

Light-Regulated Molecular Trafficking in a Synthetic Water-Soluble Host

Cucurbit[8]uril (CB[8])-mediated complexation of a dicationic azobenzene in water allows for the light-controlled encapsulation of a variety of second guest compounds, including amino acids, dyes, and fragrance molecules. Such controlled guest sequestration inside the cavity of CB[8] enables the regulation of the thermally induced phase transition of poly(N-isopropylacrylamide)-which is not photosensitive-thus demonstrating the robustness and relevancy of the light-regulated CB[8] complexation.

Quantitative multiplexing with nano-self-assemblies in SERS

Multiplexed or simultaneous detection of multiple analytes is a valuable tool in many analytical applications. However, complications caused by the presence of interfering compounds in a sample form a major drawback in existing molecular sensor technologies, particularly in multi-analyte systems. Although separating analytes through extraction or chromatography can partially address the problem of interferents, there remains a need for developing direct observational tools capable of multiplexing that can be applied in situ. Surface-enhanced Raman Spectroscopy (SERS) is an optical molecular finger-printing technique that has the ability to resolve analytes from within mixtures. SERS has attracted much attention for its potential in multiplexed sensing but it has been limited in its quantitative abilities. Here, we report a facile supramolecular SERS-based method for quantitative multiplex analysis of small organic molecules in aqueous environments such as human urine.