Supramolecularly modulated carbon-centered radicals: toward selective oxidation from benzyl alcohol to aldehyde.

The reactivity of ketyl radicals and benzoyl radicals, two key intermediates of photo-induced oxidation of benzyl alcohol, can be stabilized by the host-guest interaction of the radicals with cucurbit[7]uril. As a result, the selectivity of photo-induced oxidation from benzyl alcohol to aldehyde is significantly improved by diminishing side reactions and inhibiting the generation of carboxylic acid products. This work presents a new route to modulate the reactivity of radical intermediates, enriching the chemistry of supramolecular intermediates and the toolbox of supramolecular catalysis.

A Polymeric Nanoparticle to Co-Deliver Mitochondria-Targeting Peptides and Pt(IV) Prodrug: Toward High Loading Efficiency and Combination Efficacy.

Developing combination chemotherapy systems with high drug loading efficiency at predetermined drug ratios to achieve a synergistic effect is important for cancer therapy. Herein, a polymeric dual-drug nanoparticle composed of a Pt(IV) prodrug derived from oxaliplatin and a mitochondria-targeting cytotoxic peptide is constructed through emulsion interfacial polymerization, which processes high drug loading efficiency and high biocompatibility. The depolymerization of polymeric dual-drug nanoparticle and the activation of Pt prodrug can be effectively triggered by the acidic tumor environment extracellularly and the high levels of glutathione intracellularly in cancer cells, respectively. The utilization of mitochondria-targeting peptide can inhibit ATP-dependent processes including drug efflux and DNA damage repair. This leads to increased accumulation of Pt-drugs within cancer cells. Eventually, the polymeric dual-drug nanoparticle demonstrates appreciable antitumor effects on both cell line derived and patient derived xenograft lung cancer model. It is highly anticipated that the polymeric dual-or multi-drug systems can be applied for combination chemotherapy to achieve enhanced anticancer activity and reduced side effects.

Reversible Amidation Chemistry Enables Closed-Loop Chemical Recycling of Carbon Fiber Reinforced Polymer Composites to Monomers and Fibers.

Highly efficient recycling of carbon fiber reinforced polymer composites into monomers and fibers is a formidable challenge. Herein, we present a closed-loop recycling approach for carbon fiber reinforced polymer composites using reversible amidation chemistry, which enables the complete recovery of intact carbon fibers and pure monomers. The polymer network, synthesized by amidation between a macromonomer linear polyethyleneimine and a bifunctional maleic anhydride cross-linker, serves as a matrix for the construction of composites with exceptional mechanical properties, thermal stability and solvent resistance. The matrices can be fully depolymerized under the acidic condition at ambient temperature, allowing the effective separation and recovery of both carbon fibers and the two monomers. The reclaimed carbon fibers retain nearly identical mechanical properties to pristine ones, while pure monomers are recycled with high separation yields (>93 %). They can be reused in for multiple cycles for the manufacture of new composites, whose mechanical properties recover over 95 % of their original properties. This line of research presents a promising approach for the design of high-performance and sustainable thermoset composites, offering significant environmental and economic benefits.

A Supramolecular Naphthalene Diimide Radical Anion with Efficient NIR-II Photothermal Conversion for E. coli-Responsive Photothermal Therapy.

We report a supramolecular naphthalene diimide (NDI) radical anion with efficient NIR-II photothermal conversion for E. coli-responsive photothermal therapy. The supramolecular radical anion (NDI-2CB[7])⋅- , which is obtained from the E. coli-induced in situ reduction of NDI-2CB[7] neutral complex, formed by the host-guest interaction between an NDI derivative and cucurbit[7]uril (CB[7]), exhibits unexpectedly strong NIR-II absorption and remarkable photothermal conversion capacity in aqueous solution. The NIR-II absorption is caused by the self-assembly of NDI radical anions to form supramolecular dimer radicals in aqueous solution, which is supported by theoretically predicted spectra. The (NDI-2CB[7])⋅- demonstrates excellent NIR-II photothermal antimicrobial activity (>99 %). This work provides a new approach for constructing NIR-II photothermal agents and non-contact treatments for bacterial infections.

Stabilization of Carbocation Intermediate by Cucurbit[7]uril Enables High Photolysis Efficiency.

A cucurbit[7]uril-based host-guest strategy is employed to enhance the efficiency of photolysis reactions that release caged molecules from photoremovable protecting groups. The photolysis of benzyl acetate follows a heterolytic bond cleavage mechanism, thereby leading to the formation of a contact ion pair as the key reactive intermediate. The Gibbs free energy of the contact ion pair is lowered by 3.06 kcal/mol through the stabilization of cucurbit[7]uril, as revealed by DFT calculations, which results in a 40-fold increase in the quantum yield of the photolysis reaction. This methodology is also applicable to the chloride leaving group and the diphenyl photoremovable protecting group. We anticipate that this research presents a novel strategy to improve reactions involving active cationics, thereby enriching the field of supramolecular catalysis.

Effects of Univariate Stiffness and Degradation of DNA Hydrogels on the Transcriptomics of Neural Progenitor Cells.

Mechanical interactions between cells and extracellular matrix (ECM) are critical for stem cell fate decision. Synthetic models of ECM, such as hydrogels, can be used to precisely manipulate the mechanical properties of the cell niche and investigate how mechanical signals regulate the cell behavior. However, it has long been a great challenge to tune solely the ECM-mimic hydrogels' mechanical signals since altering the mechanical properties of most materials is usually accompanied by chemical and topological changes. Here, we employ DNA and its enantiomers to prepare a series of hydrogels with univariate stiffness regulation, which enables a precise interpretation of the fate decision of neural progenitor cells (NPCs) in a three-dimensional environment. Using single-cell RNA sequencing techniques, Monocle pseudotime trajectory and CellphoneDB analysis, we demonstrate that the stiffness of the hydrogel alone does not influence the differentiation of NPCs, but the degradation of the hydrogel that enhances cell-cell interactions is possibly the main reason. We also find that ECM remodeling facilitates cells to sense mechanical stimuli.

Reinforcing supramolecular hyaluronan hydrogels via kinetically interlocking multiple-units strategy.

Supramolecular hydrogels exhibit promising potential in biological and clinical fields due to their special dynamic properties. However, most existing supramolecular hydrogels suffer from poor mechanical strength, which severely limits their applications. Here in this study, the Kinetically Interlocking Multiple-Units (KIMU) strategy was applied to the hyaluronan networks by introducing different supramolecular interaction motifs in an organized and alternative manner. Our strategy successfully elevated the energy barrier of crosslinker dissociation to 103.0 kJ mol-1 and increased the storage modulus of hydrogels by 78 % with the intrinsic dynamic properties preserved. It can be expected that this method would bring a convenient and effective route to fabricate novel supramolecular materials with excellent mechanical properties.

Closed-loop chemical recycling of cross-linked polymeric materials based on reversible amidation chemistry.

Closed-loop chemical recycling provides a solution to the end-of-use problem of synthetic polymers. However, it remains a major challenge to design dynamic bonds, capable of effective bonding and reversible cleaving, for preparing chemically recyclable cross-linked polymers. Herein, we report a dynamic maleic acid tertiary amide bond based upon reversible amidation reaction between maleic anhydrides and secondary amines. This dynamic bond allows for the construction of polymer networks with tailorable and robust mechanical properties, covering strong elastomers with a tensile strength of 22.3 MPa and rigid plastics with a yield strength of 38.3 MPa. Impressively, these robust polymeric materials can be completely depolymerized in an acidic aqueous solution at ambient temperature, leading to efficient monomer recovery with >94% separation yields. Meanwhile, the recovered monomers can be used to remanufacture cross-linked polymeric materials without losing their original mechanical performance. This work unveils a general approach to design polymer networks with tunable mechanical performance and closed-loop recyclability, which will open a new avenue for sustainable polymeric materials.

Studies on the Synergistic Effect of Tandem Semi-Stable Complementary Domains on Sequence-Defined DNA Block Copolymers.

Tandem semi-stable complementary domains play an important role in life, while the role of these domains in the folding process of nucleic acid molecules has not been systematically studied. Here, we designed a clean model system by synthesizing sequence-defined DNA-OEG copolymers composed of ssDNA fragments with palindromic sequences and orthogonal oligo(tetraethylene glycol) (OEG) linkers. By altering the lengths of DNA units (6-12 nt) and OEG linkers (Xn = 0-4) separately, we systematically studied how stabilities of tandem complementary domains and connecting flexibilities affect the assembly topology. Combining experimental methods and coarse-grained molecular simulation analysis, distributions of multiple assembled conformations (mainly monomers, dimers, and clusters) were characterized. Both results indicated that tandem semi-stable complementary domains tend to form homogeneous closed circular dimers instead of larger clusters due to the synergistic enhancement effect, and the distributions of each conformation highly depend on flexibilities.

"Shutter" Effects Enhance Protein Diffusion in Dynamic and Rigid Molecular Networks.

Hydrogels have been widely applied to understand the fundamental functions and mechanism of a natural extracellular matrix (ECM). However, revealing the high permeability of ECM through synthetic hydrogels is still challenged by constructing analogue networks with rigid and dynamic properties. Here, in this study, taking advantage of the rigidity and dynamic binding of DNA building blocks, we have designed a model hydrogel system with structural similarity to ECM, leading to enhanced diffusion for proteins compared with a synthetic polyacrylamide (PAAm) hydrogel. The molecular diffusion behaviors in such a rigid and dynamic network have been investigated both in experiments and simulations, and the dependence of diffusion coefficients with respect to molecular size exhibits a unique transition from a power law to an exponential function. A "shutter" model based on the rigid and dynamic molecular network has been proposed, which has successfully revealed how the rigidity and dynamic bond exchange determine the diffusion mechanism, potentially providing a novel perspective to understand the possible mechanism of enhanced diffusion behaviors in ECM.

Improving Photocatalytic Performance through the Construction of a Supramolecular Organic Framework.

A supramolecular organic framework-type photocatalyst, named TM-SOF, is constructed by the self-assembly of cucurbit[8]uril and a tetra-arm monomer containing four N, N'-dimethyl 2,5-bis(4-pyridinium)thiazolo[5,4-d]thiazole (MPT) moieties. Benefiting from the multivalent assembly, a photocatalytically active supramolecular MPT dimer can be stably formed in TM-SOF. In addition, TM-SOF exhibits better stability against temperature, substrate, and light irradiation. As a result, TM-SOF shows a significantly improved performance for the photocatalytic aerobic oxidation of aryl boronic acids and thioethers. It is anticipated that this line of research will provide a facile approach for fabricating high-performance supramolecular photocatalysis systems.

A Bio-Based Supramolecular Adhesive: Ultra-High Adhesion Strengths at both Ambient and Cryogenic Temperatures and Excellent Multi-Reusability.

Developing high-performance and reusable adhesives from renewable feedstocks is of significance to sustainable development, yet it still remains a formidable task. Herein, castor oil, melevodopa, and iron ions are used as building blocks to construct a novel bio-based supramolecular adhesive (BSA) with outstanding adhesion performances. It is prepared through partial coordination between melevodopa functionalized castor oil and Fe3+ ions. Noncovalent interactions between adherends and the catechol unit from melevodopa contribute to reinforcing adhesion, and the metal-ligand coordination between catechol and Fe3+ ions is utilized to strengthen cohesion. By combining strong adhesion and tough cohesion, the prepared BSA achieves an adhesion strength of 14.6 MPa at ambient temperature, a record-high value among reported bio-based adhesives as well as supramolecular adhesives to the best of knowledge. It also outperforms those adhesives at cryogenic temperature, realizing another record-high adhesion strength of 9.5 MPa at -196 °C. In addition, the BSA displays excellent multi-reusability with more than 87% of the original adhesion strength remaining even after reuse for ten times. It is highly anticipated that this line of research will provide a new insight into designing bio-based adhesives with outstanding adhesion performances and excellent multi-reusability.

Supramolecular Polymerization at Interfaces.

Supramolecular polymers, originating from the interplay between polymer science and supramolecular chemistry, have attracted increasing interest in the scientific and industrial communities. To date, most supramolecular polymers are constructed in homogeneous solutions. Supramolecular polymerization normally takes place spontaneously in solutions, thus creating challenges in fabricating supramolecular polymers in a controlled manner. By combining supramolecular polymerization and interfacial polymerization, supramolecular polymerization can be transferred from homogeneous solutions to interfaces, which allows for the controlled production of supramolecular polymers. In this Perspective, we will summarize recent progress and the advantages in supramolecular polymerization at solid-liquid and liquid-liquid interfaces. Meanwhile, current challenges and opportunities in the field of supramolecular polymerization at interfaces are proposed and discussed. It is anticipated that this Perspective will inspire supramolecular polymerization at interfaces and facilitate the construction of supramolecular polymeric materials with diverse architectures and tailor-made functions.

A Bacteria-Responsive Porphyrin for Adaptable Photodynamic/Photothermal Therapy.

We report a cationic porphyrin 5,10,15,20-tetrakis-(4-N-methylpyridyl)-porphyrin (TMPyP) that can respond to specific bacteria, followed by adaptable photodynamic/photothermal therapy processes. TMPyP could be reduced to phlorin by facultative anaerobes with a strong reducing ability such as E. coli and S. typhimurium in hypoxic environments, possessing strong NIR absorption and remarkable photothermal conversion capacity, thus demonstrating excellent antimicrobial activity (>99 %) by photothermal therapy. While in an aerobic environment with aerobic bacteria, TMPyP functioned as a typical photosensitizer that killed bacteria effectively (>99.9 %) by photodynamic therapy. By forming a host-guest complex with cucurbit[7]uril, the biocompatibility of TMPyP significantly improved. This kind of bacteria-responsive porphyrin shows specificity and adaptivity in antimicrobial treatment and holds potential in non-invasive treatments of bacterial infections.

Degradable Bactericide Constructed Using a Charge-Reversal Surfactant against Plant Pathogenic Bacteria.

Plant bacterial diseases are serious problems in agriculture, posing threats to global food security and the agricultural economy. Here, a degradable agricultural bactericide AMC-10 constructed using a charge-reversal surfactant, from being positively charged to negatively charged, was designed and synthesized. AMC-10 possessed high bactericidal activity toward plant pathogenic bacteria, consequently being able to inhibit the corresponding plant bacterial diseases. After degradation by water, the hydrolyzed products were nontoxic to bacteria and human cells. Such a degradable bactericide provides new ideas for the design of environmentally friendly agricultural bactericides. It is anticipated that degradable bactericides such as AMC-10 can be applied in the prevention and control of plant bacterial diseases, being less likely to produce toxicity or drug resistance.

In Situ Hypoxia-Induced Supramolecular Perylene Diimide Radical Anions in Tumors for Photothermal Therapy with Improved Specificity.

Considering that hypoxia is closely associated with tumor proliferation, invasion, metastasis, and drug resistance, it is of great significance to overcome hypoxia in tumor treatment. Herein, we report a hypoxia-induced specific photothermal therapy (PTT) based on the photothermal agent of supramolecular perylene diimide radical anions. Hypoxic regions in various tumors display strong reductive ability, and in such environments the supramolecular complex of a perylene diimide derivative and cucurbit[7]uril could be reduced to supramolecular perylene diimide radical anions. Benefiting from the strong NIR absorption and good photothermal conversion performance of the in situ generated supramolecular perylene diimide radical anions, the hypoxia-induced PTT strategy exhibits excellent photothermal therapeutic efficiency as well as good specificity and biological safety. Moreover, hypoxia inducible factor expression of tumors decreases to the normal level after PTT treatment. It is anticipated that such a hypoxia-induced specific PTT strategy opens new horizons for photothermal therapy against hypoxic tumors with improved specificity and safety.

Cucurbit[7]uril-Modulated H/D Exchange of α-Carbonyl Hydrogen: Deceleration in Alkali and Acceleration in Acid Conditions.

Supramolecular catalysis based on host-guest interactions has aroused much attention in past decades. Among the various strategies, modulation of the reactivity of key intermediates is an effective strategy to achieve high-efficiency supramolecular catalysis. Here, we report that by utilizing the host-guest interaction of cucurbit[7]uril (CB[7]), the reactivity of anionic enolate and cationic oxonium, the intermediates of H/D exchange of the α-carbonyl hydrogen in alkali and acid conditions, respectively, could be modulated effectively. On one hand, in alkaline conditions, both the electrostatic effect and the steric hindrance effect of CB[7] disfavored formation of the enolate anion intermediate. On the other hand, in acidic conditions, the oxonium was stabilized and the solvent effect was weakened by the electrostatic effect of CB[7]. As a result, the H/D exchange of 1-(4-acetylphenyl)-N,N,N-trimethylmethanaminium bromide is decelerated in alkaline and accelerated in acidic conditions. It is promising that the highly polar portals of CB[n] molecules together with their well-defined host-guest chemistry may be applied to modulate the reactivity of other kinds of ionic intermediates in an effective and convenient way, thus enriching the toolkit of supramolecular catalysis.

An Activatable Host-Guest Conjugate as a Nanocarrier for Effective Drug Release through Self-Inclusion.

There is a challenge in supramolecular chemotherapy for constructing a system equipped with both sufficient protection and high-efficiency release of drugs. To this end, a new strategy of an activatable host-guest conjugate with self-inclusion property is proposed. Based on the binding affinity gain of intramolecular host-guest self-inclusion, an activatable host-guest conjugate was designed, bearing cucurbit[7]uril as the host, an alkyl ammonium moiety as the guest, and the redox-responsive disulfide linkage. Oxaliplatin, a clinical antitumor drug, could be firmly encapsulated by the activatable host-guest conjugate to form the supramolecular drug with high stability. Moreover, oxaliplatin loaded in the activatable host-guest conjugate could be almost completely released by self-inclusion triggered by glutathione in a tumor microenvironment, thus exhibiting comparable antitumor bioactivity with naked oxaliplatin through in vitro cell experiments. It is highly anticipated that this line of research may open new horizons for programmable and on-demand supramolecular chemotherapy with high antitumor efficiency.

Kinetically Interlocking Multiple-Units Polymerization of DNA Double Crossover and Its Application in Hydrogel Formation.

A novel kinetically interlocking multiple-units (KIMU) supramolecular polymerization system with DNA double crossover backbone is designed. The rigidity of DX endows the polymer with high molecular weight and stability. The observed concentration of the formed polymers is insensitive and stable under ultralow monomer concentration owing to the KIMU interactions, in which multiple noncovalent interactions are connected by the phosphodiester bonds. Furthermore, a pH-responsive DNA supramolecular hydrogel is constructed by introducing a half i-motif domain into the DNA monomer. The rigidity of DNA polymer endows the hydrogel with high mechanical strength and low gelation concentration. This study enriches the KIMU strategy and offers a simple but effective way to fabricate long and stable supramolecular polymers by balancing the reversibility and stability. It also shows great potentials to construct next generation of smart materials, such as DNA nanostructures, DNA motors, and DNA hydrogels.

Fluorescence "Turn-On" Enzyme-Responsive Supra-Amphiphile Fabricated by Host-Guest Recognition between γ-Cyclodextrin and a Tetraphenylethylene-Sodium Glycyrrhetinate Conjugate.

A novel fluorescence "turn-on" enzyme-responsive supra-amphiphile is developed based on the host-guest recognition between γ-cyclodextrin (γ-CD) and an amphiphilic tetraphenylethene-sodium glycyrrhetinate conjugate (TPE-SGA). The covalent amphiphile TPE-SGA displayed strong fluorescence in aqueous solution owing to the aggregation-induced emission. Upon addition of γ-CD, the fluorescence of TPE-SGA was effectively turned off due to the host-guest recognition with γ-CD prohibiting the aggregation of TPE-SGA in aqueous solution. The as-formed nonfluorescent supra-amphiphile (TPE-SGA/γ-CD) inherited the α-amylase-responsive property of γ-CD. In the presence of α-amylase, the fluorescence of the supra-amphiphile was gradually turned on owing to the hydrolysis of γ-CD, and the fluorescence intensity linearly correlated to the activity of α-amylase. This study enriches the field of supra-amphiphile on the basis of cyclodextrin-based host-guest chemistry and provides a novel strategy to construct fluorescence turn-on functioned self-assemblies. It is anticipated that the fluorescence turn-on supra-amphiphile has potential applications in biological analysis and diagnosis of pancreatic diseases.