Noncovalent Strategy Research Articles

Supramolecular Polymer Additives as Repairable Reinforcements for Dynamic Covalent Networks.

Employing rigid (in)organic materials as reinforcement for dynamic covalent networks (DCNs) is an effective approach to develop high-performance materials. Yet, recycling of these materials after failure often necessitates inefficient chemical reprocessing or inevitably alters their performance due to unrepairable inert components. Here, a non-covalent reinforcement strategy is presented by introducing a supramolecular additive to a DCN that can reversibly depolymerize and reform on demand, therefore acting as an adaptive and repairable reinforcement. The strong hydrogen-bonding interactions in the supramolecular polymer of triazine-1,3,5-tribenzenecarboxamide (S-T) strengthen the DCN at room temperature, while its non-covalent nature allows for easy one-pot reprocessing at high temperatures. Depending on wether S-T is covalently bond to the DCN or not, it can play either the role of compatibilizer or filler, providing a synthetic tool to control the relaxation dynamics, reprocessability and mechanical properties. Moreover, the S-T reinforcement can be chemically recovered with high yield and purity, showcasing the recyclability of the composite. This conceptually novel supramolecular reinforcement strategy with temperature-controlled dynamics highlights the potential of supramolecular polymer additives to replace conventional unrepairable reinforcements.

Gallocyanine-mediated non-covalent functionalization and exfoliation of h-BN for efficient anticorrosion reinforcement of waterborne epoxy coating

Hexagonal boron nitride (h-BN) is commonly used to enhance the anti-corrosion of organic coatings due to its excellent barrier properties, dielectricity and mechanical robustness. However, the bulky h-BN tends to create poor dispersibility and interfacial compatibility problems with the resin matrix, leading to coating cracking and failure. H-BN nanosheets exfoliated by conventional methods only provide passive barrier effect with coatings at the initial stage of corrosion. Herein, we used a mussel-inspired non-covalent functionalization strategy, using the catechol groups and heteroaromatic ring structure of gallocyanine to achieve the functionalization and exfoliation of h-BN through ball milling, and obtained ultra-thin h-BN@G nanosheets. Remarkably, spare gallocyanine can further suppress the erosion, whose inhibition efficiency is 95.48 % at the concentration of 100 mg/L in 1 M HCl within 9 h. Typically, after 105 days of immersion in 3.5 wt% NaCl solution, the low-frequency impedance of h-BN@G/WEP coating is still as high as 1.45 × 109 Ω cm2, which is two orders of magnitude higher than that of the pure coating. The superior long-term anti-corrosion capacity can be ascribed to the triple protection of enhanced shielding property of desirable-exfoliated h-BN, passivation films adsorbed on the metal and coordination bonds formed between gallocyanine and the iron to resist the active corrosion. Our work offers an innovative idea for the functionalization and exfoliation of other lamellar materials, which can be applied to the implementation of long-lasting anti-corrosion coatings.

Esterase-Responsive Floxuridine-Tethered Multifunctional Nanoparticles for Targeted Cancer Therapy.

Floxuridine is a potential clinical anticancer drug for the treatment of various cancers. However, floxuridine typically causes unfavorable side effects due to its very poor tumor selectivity, and, hence, there is a high demand for the development of novel approaches that permit the targeted delivery of floxuridine into cancerous cells. Herein, the design and synthesis of an esterase-responsive multifunctional nanoformulation for the targeted delivery of floxuridine in esterase-overexpressed cancer cells is reported. Photopolymerization of floxuridine-tethered lipoic acid results in the formation of amphiphilic floxuridine-tethered poly(disulfide). Self-assembly of the amphiphilic polymer results in the formation of nanoparticles with floxuridine decorated on the surfaces of the particles. Integration of aptamer DNA for nucleolin onto the surface of the nanoparticle is demonstrated by exploring the base-pairing interaction of floxuridine with adenine. Targeted internalization of the aptamer-decorated nanoparticle into nucleolin-expressed cancer cells is demonstrated. Esterase triggered cleavage of the ester bond connecting floxuridine with the polymer backbone, and the subsequent targeted delivery of floxuridine into cancer cells is also shown. Excellent therapeutic efficacy is observed both in vitro and also in the 3D tumor spheroid model. This noncovalent strategy provides a simple yet effective strategy for the targeted delivery of floxuridine into cancer cells in a less laborious fashion.

Novel synthesis of thermoresponsive single-walled carbon nanotubes/poly(N-isopropylacrylamide) hybrids

Poly(N-isopropylacrylamide) (PNIPAM) is one of the most well studied thermoresponsive polymers and its microgels undergo a reversible volume phase transition (VPT) at temperatures close to that of the human body. Coupling this property with the unique optical properties of single-walled carbon nanotubes (SWCNT) in the near infrared (NIR) leads to interesting nanohybrids that could be used as multi-responsive sensors/actuators for biological applications.We show the synthesis of thermoresponsive SWCNT/PNIPAM hybrids using two different non-covalent strategies, preserving the nanotube optical properties such as fluorescence. The first strategy involves the dispersion of the SWCNT in water with sodium dodecyl sulfate (SDS), and subsequent in situ synthesis of PNIPAM microgels inside the SDS coatings around the nanotubes. The second strategy starts with modifying the nanotubes with a pyrene derivative, which in turn is used as the starting point for the in situ polymerization of the PNIPAM microgels, thus ensuring that the polymer grows around the nanotubes. In both cases, we obtain hybrids showing a phase transition at temperatures close to that of the human body, with the absorption and fluorescence spectra of the hybrids in the NIR changing in response to the changing dielectric environment. These systems could be used as actuators/sensors in biological systems.

Supramolecular Assembly Frameworks (SAFs): Shaping the Future of Functional Materials.

Supramolecular assembly frameworks (SAFs) represent a new category of porous materials, utilizing non-covalent interactions, setting them apart from metal-organic frameworks (MOFs) and covalent organic frameworks (COFs). This category includes but is not restricted to hydrogen-bonded organic frameworks and supramolecular organic frameworks. SAFs stand out for their outstanding porosity, crystallinity, and stability, alongside unique dissolution-recrystallization dynamics that enable significant structural and functional modifications. Crucially, their non-covalent assembly strategies allow for a balanced manipulation of porosity, symmetry, crystallinity, and dimensions, facilitating the creation of advanced crystalline porous materials unattainable through conventional covalent or coordination bond synthesis. Despite their considerable promise in overcoming several limitations inherent to MOFs and COFs, particularly in terms of solution-processability, SAFs have received relatively little attention in recent literature. This Minireview aims to shed light on standout SAFs, exploring their design principles, synthesis strategies, and characterization methods. It emphasizes their distinctive features and the broad spectrum of potential applications across various domains, aiming to catalyze further development and practical application within the scientific community.

Dispersion of Single-Walled Carbon Nanotubes by Aromatic Cyclic Schiff Bases via Non-Covalent Interactions.

One of the challenging issues that hinders the application of single-walled carbon nanotubes (SWCNTs) is the poor solubility and the inevitable formation of bundles. Efforts still need to be made towards solving the problem. Herein, we report a non-covalent strategy to disperse aggregated SWCNTs by aromatic cyclic Schiff bases assisted by ultrasonic techniques. The aromatic cyclic Schiff base (OMM) was synthesized via Schiff base reactions, and the molecular structure was determined by ATR-FT-IR, solid-state 13C-NMR, and HRMS. Although the yielded product showed poor solubility in aqueous solution and organic solvents, it could interact with and disperse the aggregated SWCNTs in dimethyl formamide (DMF) under the condition of ultrasound. UV-vis-NIR, FL, Raman spectra, AFM, and TEM, along with computer simulations, provide evidence for the interactions between OMM molecules and SWCNTs and the dispersion thereof. The semiconductive (7,5), (8,6), (12,1), and (9,7)-SWCNTs expressed a preference for dissolution. The capability of dispersion is contributed by π-π, C-H·π, and lone pair (lp)·π interactions between OMM and SWCNTs based on the simulated results. The present non-covalent strategy could provide inspiration for preparing organic cyclic compounds as dispersants for SWCNTs and then facilitate their further utilization.

Noncovalent Assembly Strategy for Efficient Synthesis of Dual‐Atom Catalysts

AbstractDiatomic catalysts (DACs), as a frontier of research on atomically dispersed catalysts, have drawn great attention, especially in electrocatalysis. However, most of the current synthetic strategies for DACs suffer from poor efficiency and high cost. In this work, a novel noncovalent assembly strategy is reported for the efficient synthesis of DACs. By the aid of two kinds of noncovalent intermolecular force, the π–π stacking and Coulomb forces, a pair of metal complex ions with opposite electrical charges is spontaneously loaded onto the carbon substrate and transformed into diatomic sites via thermal treatment. This noncovalent assembly approach shows universal feasibility for a broad spectrum of DACs (Ir–Fe, Pt–Fe, Pt–Co, and Pt–Ni). To prove the practical utility, the as‐prepared PtFe‐DAC is deployed as oxygen reduction reaction catalyst, performing excellent activity with a half‐wave potential of 0.935 V (vs RHE) and a 2.3 times higher turnover frequency than that of the single‐atomic Fe‐SAC. In situ characterization and theoretical calculation indicate that the adjacent Pt sites could endow moderate activation of oxygen molecule on Fe sites by lowering the electron pairing energy as well as the modulation of the d‐band center and spin states of Fe centers propelling the desorption of the intermediates.

Fabrication of magnetic molecularly imprinted polymer-based covalent–noncovalent synergistic imprinting strategies for the highly specific enrichment of luteolin from honeysuckle

Fabrication of magnetic molecularly imprinted polymer-based covalent–noncovalent synergistic imprinting strategies for the highly specific enrichment of luteolin from honeysuckle

Riboflavin-induced photo-ATRP electrochemical strategy for detection of biomarker trypsin

The detection of trypsin and its inhibitors is important for both clinical diagnosis and disease treatment. Abnormal trypsin activity affects pancreatic function and leads to corresponding pathological changes in the body. Therefore, the study presented a riboflavin-induced photo-ATRP electrochemical assay of trypsin activity and its inhibitor, including detection of trypsin activity in real urine samples. Experiments were performed on indium tin oxide (ITO) electrodes modified with sulfhydryl groups of 3-mercaptopropionic acid, and target trypsin-specific cleavage of BSA-Au nanocluster (BSA-Au NCs) was followed by the modification of Au NCs to the electrodes using Au–S. The Au NCs immobilized monodeoxy-monomercapto-β-cyclodextrin@adamantan-2-amine (SH-β-CD@2-NH2-Ada) host-guest inclusion complexes to the electrode surfaces via Au–S. In a two-component photo-initiator system consisting of riboflavin as an initiator and ascorbic acid (AA) as a mild reducing agent under mild blue light radiation, a large number of electroactive substances were grafted onto the electrode surface to generate electrochemical signals. In addition, we have successfully realized the detection of clinical drug inhibitors of trypsin. The detection limit of the system is as low as 0.0024 ng/mL, which much littler than the average standard of trypsin in the patient's urine or serum. It's worth noting that this work will provide researchers with a different route to design electrochemical sensors based on non-covalent recognition strategies.

Synergy between Laminin-Derived Elastin-like Polypeptides (LELPs) Optimizes Cell Spreading.

A major component of the extracellular matrix (ECM), laminins, modulates cells via diverse receptors. Their fragments have emerging utility as components of "ECM-mimetics" optimized to promote cell-based therapies. Recently, we reported that a bioactive laminin peptide known as A99 enhanced cell binding and spreading via fusion to an elastin-like polypeptide (ELP). The ELP "handle" serves as a rapid, noncovalent strategy to concentrate bioactive peptide mixtures onto a surface. We now report that this strategy can be further generalized across an expanded panel of additional laminin-derived elastin-like polypeptides (LELPs). A99 (AGTFALRGDNPQG), A2G80 (VQLRNGFPYFSY), AG73 (RKRLQVQLSIRT), and EF1m (LQLQEGRLHFMFD) all promote cell spreading while showing morphologically distinct F-actin formation. Equimolar mixtures of A99:A2G80-LELPs have synergistic effects on adhesion and spreading. Finally, three of these ECM-mimetics promote the neurite outgrowth of PC-12 cells. The evidence presented here demonstrates the potential of ELPs to deposit ECM-mimetics with applications in regenerative medicine, cell therapy, and tissue engineering.

Benzodipyrrolidone-based donor-acceptor semiconducting polymers with high hole mobility and noncovalent conformational locks

Constructing highly coplanar polymer backbone plays an important role in boosting the carrier mobility of organic field effect transistors (OFETs) devices. In this study, based on noncovalent conformational locks strategy, we synthesized the electron-acceptor (A) monomer via introducing 3-dodecylthiophene on strong electron-deficient planar benzodipyrrolidone and the electron-donor (D) monomers containing different numbers (0–2) of fluorine atoms at different positon. A series of novel D-A copolymers, namely PBDP-F0, PBDP-F1 and PBDP-F2 with different backbone conformational locks through F⋯S and F⋯H–C noncovalent interactions, were obtained via Stille polycondensation. For the application in an organic field-effect transistor, all the polymers exhibited p-type charge transport characteristics and good performance with the highest hole mobilities as 0.24 cm2 V−1 s−1 for PBDP-F0, 0.87 cm2 V−1 s−1 for PBDP-F1 and 1.93 cm2 V−1 s−1 for PBDP-F2, respectively. AFM and GIXRD investigations indicated that all polymers take predominantly edge-on orientation packing mode because of the rigid and coplanar backbone conformation and the annealing films exhibited small π-π stacking distances of 3.73, 3.71 and 3.69 Å for PBDP-F0, PBDP-F1 and PBDP-F2 respectively. This work demonstrates that modified BDP-based D-A copolymers with conformational locks has a potential application in the high-performance semiconductor materials.

Doping heteroatoms to form multiple hydrogen bond sites for enhanced interfacial reconstruction and separations

Interfacial challenges in unconventional oil extraction include heavy oil–water–solid multiphase separation and corrosion inhibition. Herein, a novel strategy based on interfacial hydrogen bonding reconstruction is proposed for constructing multifunctional interfacially active materials (MIAMs) to address multi-interfacial separation needs. A simple one-pot method is applied to successfully synthesize four different MIAM varieties, integrating site groups (–NH2, OSO, –COOH, and Si–O–Si) with multiple hydrogen bonds (HBs) into allyl polyether chains. The results indicate that all synthesized MIAMs excel in demulsification, detergency, and corrosion inhibition simultaneously, even at 25 °C. Their dehydration efficiency for different water-in-oil emulsions (even heavy oil emulsion) surpasses 99.9 % even at 16 °C, showing their excellent energy-saving potential for field applications. Furthermore, they demonstrate effective, nondestructive static cleaning (up to 86 %) of adhered oil from solid surfaces at 25 °C and provide corrosion inhibition effects (up to 92.09 %) on mild steel immersed in saturated brine. Mechanistic tests reveal that incorporating multiple HB sites in MIAMs dramatically enhances their effectiveness in interfacial separations. Based on these findings, an HB-dominated noncovalent interaction reconstruction strategy is tentatively proposed to develop advanced materials for low-carbon, efficient interfacial separations.

Acetone Serving as a Solvent and Interaction Partner Promotes the Direct Olefination of N-Tosylhydrazones under Visible Light.

The photochemistry of noncovalent interactions to promote organic transformations is an emerging approach to providing fresh opportunities in synthetic chemistry. Generally, the external substance is necessary to add as an interaction partner, thereby sacrificing the atom economy of the reaction. Herein, we describe a catalyst-free and noncovalent interaction-mediated strategy to access the olefination of N-tosylhydrazones using acetone as a solvent and an interaction partner. This protocol also features broad substrate scope, excellent functional group compatibility, and mild reaction conditions without transition metals. Moreover, the gram-scale synthesis of olefins and the generation of pharmaceutical intermediates highlighted its practical applicability. Lastly, mechanistic studies indicate that the reaction was initiated via noncovalent interactions between acetone and N-tosylhydrazone anion, which is also supported by density functional theory calculations.

Building ultra-stable and low-temperature aqueous zinc–organic batteries via noncovalent supramolecular self-assembly strategy

Zinc-organic batteries (ZOB) have garnered significant attention owing to their design flexibility and abundant raw materials. However, a notable drawback arises from the tendency of organic electrodes to dissolve in the electrolyte during cycling, resulting in diminished cycle stability and a shortened lifespan. Herein, we propose a noncovalent supramolecular self-assembly approach to address the challenge of organic electrode dissolution, namely the hydrogen-bonded organic polymer (HOP) is introduced as the cathode ensuring the electrolyte/electrode stability in ZOB. The HOP comprises perylene anhydride units characterized by robust strong π-π stacking and hydrogen bond connections. This configuration enables the reversible storage of Zn2+/H3O+ through CO/CO bond conversion, as validated by in-situ ATR-FTIR and ex-situ XPS analyses. Employing a 1 m Zn(OTF)2 electrolyte, the Zn//HOP cell exhibited stable cycling at room temperature for 20,000 cycles with nearly 80 % capacity retention and operated at –5 °C for 300 cycles with 100 % capacity retention. Our findings explore the noncovalent supramolecular self-assembly strategy in producing organic electrodes resistant to dissolution.

A co-assembly platform engaging macrophage scavenger receptor A for lysosome-targeting protein degradation

Targeted degradation of proteins has emerged as a powerful method for modulating protein homeostasis. Identification of suitable degraders is essential for achieving effective protein degradation. Here, we present a non-covalent degrader construction strategy, based on a modular supramolecular co-assembly system consisting of two self-assembling peptide ligands that bind cell membrane receptors and the protein of interest simultaneously, resulting in targeted protein degradation. The developed lysosome-targeting co-assemblies (LYTACAs) can induce lysosomal degradation of extracellular protein IL-17A and membrane protein PD-L1 in several scavenger receptor A-expressing cell lines. The IL-17A-degrading co-assembly has been applied in an imiquimod-induced psoriasis mouse model, where it decreases IL-17A levels in the skin lesion and alleviates psoriasis-like inflammation. Extending to asialoglycoprotein receptor-related protein degradation, LYTACAs have demonstrated the versatility and potential in streamlining degraders for extracellular and membrane proteins.

Superior Intermolecular Noncovalent Interactions Empowered Dopant‐Free Hole Transport Materials for Efficient and Stable Sb2(S,Se)3 Solar Cells

AbstractAntimony selenosulfide (Sb2(S,Se)3) solar cells are critically restrained by the Sb2(S,Se)3/charge transport layer interface with scarce carriers transfer ability and high density of deep‐level defect‐induced traps, which are prone to spark the nonradiative recombination and capture the benign photogenerated carriers. Herein, utilizing the intermolecular noncovalent interactions strategy in molecular stereoscopic structural engineering, two dopant‐free hole transport materials (HTMs) are constructed, coded as T‐BDT and F‐BDT, with synergistic hole selectivity and interfacial healing ability. The theoretical simulation and experimental results decipher that the F‐BDT possesses the more favorable planarized conformation, charge delocalization/coupling and molecular stacking pattern, which endow it with the salient hole selection, robust interface passivation and appropriate energy level alignment. Consequently, the Sb2(S,Se)3 solar cell with F‐BDT as dopant‐free HTM realize an outstanding power conversion efficiency of 9.13%, hitting the record high for Sb2(S,Se)3 devices under dopant‐free conditions.

Hyaluronic acid-functionalized graphene-based nanohybrids for targeted breast cancer chemo-photothermal therapy

Nanomaterials’ application in cancer therapy has been driven by their ability to encapsulate chemotherapeutic drugs as well as to reach the tumor site. Nevertheless, nanomedicines’ translation has been limited due to their lack of specificity towards cancer cells. Although the nanomaterials’ surface can be coated with targeting ligands, such has been mostly achieved through non-covalent functionalization strategies that are prone to premature detachment. Notwithstanding, cancer cells often establish resistance mechanisms that impair the effect of the loaded drugs. This bottleneck may be addressed by using near-infrared (NIR)-light responsive nanomaterials. The NIR-light triggered hyperthermic effect generated by these nanomaterials can cause irreversible damage to cancer cells or sensitize them to chemotherapeutics’ action. Herein, a novel covalently functionalized targeted NIR-absorbing nanomaterial for cancer chemo-photothermal therapy was developed. For such, dopamine-reduced graphene oxide nanomaterials were covalently bonded with hyaluronic acid, and then loaded with doxorubicin (DOX/HA-DOPA-rGO). The produced nanomaterials showed suitable physicochemical properties, high encapsulation efficiency, and photothermal capacity. The in vitro studies revealed that the nanomaterials are cytocompatible and that display an improved uptake by the CD44-overexpressing breast cancer cells. Importantly, the combination of DOX/HA-DOPA-rGO with NIR light reduced breast cancer cells’ viability to just 23 %, showcasing their potential chemo-photothermal therapy.

A noncovalent backbone planarization strategy increases the NIR-II extinction coefficients for gas/phototheranostic applications.

We propose a noncovalent backbone planarization strategy to fabricate a gas/phototheranostic nanocomposite (B-E-NO NPs) in the near-infrared-II (NIR-II, 1000-1700 nm) window by incorporating noncovalent conformational locks. B-E-NO NPs display a giant NIR-II extinction coefficient, realizing multimodal imaging-guided high-efficiency NIR-II photothermal therapy (η = 45.4%) and thermal-initiated nitric oxide combination therapy.

A co-assembly process for high strength and injectable dual network gels with sustained doxorubicin release performance.

Adopting a non-covalent co-assembly strategy shows great potential in loading drugs efficiently and safely in drug delivery systems. However, finding an efficient method for developing high strength gels with thixotropic characteristics is still challenging. In this work, by hybridizing the low molecular weight gelator fluorenylmethyloxycarbonyl-phenylalanine (Fmoc-F) (first single network, 1st SN) and alginate (second single network, 2nd SN) into a dual network (DN) gel, gels with high strength as well as thixotropy were prepared efficiently. The DN gels showed high strength (103 Pa in SN gels and 105 Pa in DN gels) and thixotropic characteristics (yield strain <25%; recovery ratio >85% within 100 seconds). The application performance was verified by loading doxorubicin (DOX), showing better encapsulation capacity (77.06% in 1st SN, 59.11% in 2nd SN and 96.71% in DN) and sustained release performance (lasting one week under physiological conditions) than single network gels. Experimental and DFT results allowed the elaboration of the specific non-covalent co-assembly mechanism for DN gel formation and DOX loading. The DN gels were formed by co-assembly driven by H-bond and π-π stacking interactions and then strengthened by Ca2+-coupling. Most DOX molecules co-assembled with Fmoc-F and alginate through π-π stacking and H-bond interactions (DOX-I), with a few free DOX molecules (DOX-II) left. Proven by the release dynamics test, DOX was released through a diffusion-erosion process, in an order of DOX-I first and then DOX-II. This work suggests that non-covalent co-assembly is a useful technique for effective material strengthening and drug delivery.

Visible-light-mediated catalyst-free synthesis of trifluoromethyl(spiro)-epoxides bearing contiguous quaternary centers

Herein, we describe a non-covalent complex-mediated epoxidation strategy that can yield highly selective central spiro-epoxides by irradiation with visible light without the need for catalyst addition.