Stimuli-responsive Behavior Research Articles

Effect of Polymorphism on the Sorption Properties of a Flexible Square-Lattice Topology Coordination Network.

The stimulus-responsive behavior of coordination networks (CNs), which switch between closed (nonporous) and open (porous) phases, is of interest because of its potential utility in gas storage and separation. Herein, we report two polymorphs of a new square-lattice (sql) topology CN, X-sql-1-Cu, of formula [Cu(Imibz)2]n (HImibz = {[4-(1H-imidazol-1-yl)phenylimino]methyl}benzoic acid), isolated from the as-synthesized CN X-sql-1-Cu-(MeOH)2·2MeOH, which subsequently transformed to a narrow pore solvate, X-sql-1-Cu-A·MeOH, upon mild activation (drying in air or heating at 333 K under nitrogen). X-sql-1-Cu-A·MeOH contains MeOH in cavities, which was removed through exposure to vacuum for 2 h, yielding the nonporous (closed) phase X-sql-1-Cu-A. In contrast, a more dense polymorph, X-sql-1-Cu-B, was obtained by exposing X-sql-1-Cu-(MeOH)2·2MeOH directly to vacuum for 2 h. Gas sorption studies conducted on X-sql-1-Cu-A and X-sql-1-Cu-B revealed different switching behaviors to two open phases (X-sql-1-Cu·CO2 and X-sql-1-Cu·C2H2), with different gate-opening threshold pressures for CO2 at 195 K and C2H2 at 278 K. Coincident CO2 sorption and in situ powder X-ray diffraction studies at 195 K revealed that X-sql-1-Cu-A transformed to X-sql-1-Cu-B after the first sorption cycle and that the CO2-induced switching transformation was thereafter reversible. The results presented herein provide insights into the relationship between two polymorphs of a CN and the effect of polymorphism upon gas sorption properties. To the best of our knowledge, whereas sql networks such as X-sql-1-Cu are widely studied in terms of their structural and sorption properties, this study represents only the second example of an in-depth study of the sorption properties of polymorphic sql networks.

Photoresponsive Azobenzene Nanocluster-Modified Liposomes: Mechanism Analysis Combining Experiments and Simulations.

Stimuli-responsive behaviors and controlled release in liposomes are pivotal in nanomedicine. To this end, we present an approach using a photoresponsive azobenzene nanocluster (AzDmpNC), prepared from azobenzene compounds through melting and aggregation. When integrated with liposomes, they form photoresponsive vesicles. The morphology and association with liposomes were investigated by using transmission electron microscopy. Liposomes loaded with calcein exhibited a 9.58% increased release after UV exposure. To gain insights into the underlying processes and elucidate the mechanisms involved. The molecular dynamic simulations based on the reactive force field and all-atom force field were employed to analyze the aggregation of isomers into nanoclusters and their impacts on phospholipid membranes, respectively. The results indicate that the nanoclusters primarily aggregate through π-π and T-stacking forces. The force density inside the cis-isomer of AzDmpNC formed after photoisomerization is lower, leading to its easier dispersion, rapid diffusion, and penetration into the membrane, disrupting the densification.

Enzyme-Triggered Polyelectrolyte Complex for Responsive Delivery of α-Helical Polypeptides to Optimize Antibacterial Therapy.

Responsive nanomaterials hold significant promise in the treatment of bacterial infections by recognizing internal or external stimuli to achieve stimuli-responsive behavior. In this study, we present an enzyme-responsive polyelectrolyte complex micelles (PTPMN) with α-helical cationic polypeptide as a coacervate-core for the treatment of Escherichia coli (E. coli) infection. The complex was constructed through electrostatic interaction between cationic poly(glutamic acid) derivatives and phosphorylation-modified poly(ethylene glycol)-b-poly(tyrosine) (PEG-b-PPTyr) by directly dissolving them in aqueous solution. The cationic polypeptide adopted α-helical structure and demonstrated excellent broad-spectrum antibacterial activity against both Gram-negative and Gram-positive bacteria, with a minimum inhibitory concentration (MIC) as low as 12.5 μg mL-1 against E. coli. By complexing with anionic PEG-b-PPTyr, the obtained complex formed β-sheet structures and exhibited good biocompatibility and low hemolysis. When incubated in a bacterial environment, the complex cleaved its phosphate groups triggered by phosphatases secreted by bacteria, exposing the highly α-helical conformation and restoring its effective bactericidal ability. In vivo experiments confirmed accelerated healing in E. coli-infected wounds.

Peptide-conjugated Nanoparticle Platforms for Targeted Delivery, Imaging, and Biosensing Applications.

Peptides have become an indispensable tool in engineering of multifunctional nanostructure platforms for biomedical applications such as targeted drug and gene delivery, imaging and biosensing. They can be covalently incorporated into a variety of nanoparticles (NPs) including polymers, metallic nanoparticles, and others. Using different bioconjugation techniques, multifunctional peptide-modified NPs can be formulated to produce therapeutical and diagnostic platforms offering high specificity, lower toxicity, biocompatibility, and stimuli responsive behavior. Targeting peptides can direct the nanoparticles into specific tissues for targeted drug and gene delivery and imaging applications due to their specificity towards certain receptors. Furthermore, due to their stimuli-responsive features, they can offer controlled release of therapeutics into desired sites of disease. In addition, peptide-based biosensors and imaging agents can provide non-invasive detection and monitoring of diseases including cancer, infectious diseases, and neurological disorders. In this review, we covered the design and formulation of recent peptide-based NP platforms, as well as their utilization in in vitro and in vivo applications such as targeted drug and gene delivery, targeting, sensing, and imaging applications. In the end, we provided the future outlook to design new peptide conjugated nanomaterials for biomedical applications.

Competition in formation of stimuli-responsive metallogel and coordination polymers from a single precursor: synthesis, characterization and catalytic application

The synthesis, structure, and catalytic properties of a new 2D crystalline coordination polymer (Zn-CP1) as well as a stable new low molecular weight metallogel (Zn-G1) are reported. Interestingly, both types of materials can be synthesized using the same amino acid based chiral ligand (PV) and Zn2+ ion. Precisely, pure organic solvent (MeOH) prompts gelation while DMF-water medium favours the formation of coordination polymer (CP). Hence, the nature of the solvents and metal counter anion used, play a crucial role in gel formation. Both the CP and gel were characterized by various spectroscopic and analytical techniques such as PXRD, FT-IR, TGA, SEM, and dynamic rheology. Structural analysis of Zn-G1 reveals an entangled spongy-like fibrous network in which spongy patches consist of micro fibres within the matrix of the supramolecular metallogel, while the structural analysis of Zn-CP1 revealed the formation of a 2D sheet-like structure. The Zn-G1 exhibits remarkable stimuli-responsive behaviour towards temperature, mechanical force, and chemicals; however, the Zn-CP1 was found to exhibit promising catalytic activity over Zn-G1 for the conversion of CO2 to cyclic carbonate from various epoxides.

Controllable Regulation of Diesel Oil-in-Water Pickering Emulsion Stability by Multiresponsive Recyclable Magnetic Polymer Brush Microvessels.

To ensure safety and efficiency in the production and transportation of fuel oil, there is an urgent demand to develop intelligent emulsifiers to deal with this challenge. Fe3O4@PDA-P(NIPAM-b-MAA-b-LMA) (MNPDNML) microspheres were prepared by modifying polydopamine and the triblock polymer brush P(NIPAM-b-MAA-b-LMA) on the surface of Fe3O4 nanoparticles via oxidative autopolymerization and SI-RAFT polymerization. Therefore, the MNPDNML microspheres exhibited sensitive stimulus-responsive behavior to pH, temperature, near-infrared (NIR) laser radiation, and magnetic fields. The stability state of the emulsion could be modulated by changing pH, temperature, magnetic field, and NIR radiation, and the reversible switching of emulsification/breaking behavior could be reached at least 10 times. This "intelligent emulsifier" exhibited high emulsification efficiency, long-term stability, and on-demand emulsification/breaking properties. It was notable that MNPDNML microspheres showed excellent emulsification ability for olive oil, kerosene, gasoline, and crude oil, which allowed the material to be widely used in the controlled transportation and separation of fuel oil.

Structure–Activity Relationship and Stimuli-Responsiveness Behavior of Metallosupramolecular Polymers

The widespread discourse on the circular economy has fueled a growing demand for polymeric materials characterized by mechanical robustness, sustainability, renewability, and the ability to mend defects. Such materials can be crafted using dynamic covalent bonds, albeit rarely or more efficiently through noncovalent interactions. Metal–ligand interactions, commonly employed by living organisms to adapt to environmental changes, play a pivotal role in this endeavor. Metallosupramolecular polymers (MSPs), formed through the incorporation of metal–ligand interactions, present a versatile platform for tailoring physicochemical properties. This review explores recent advancements in MSPs achieved through the assembly of (macro)monomers via reversible metal–ligand interactions. Various strategies and pathways for synthesizing these materials are discussed, along with their resulting properties. The review delves into the stimuli-responsive behavior of coordination metal–ligand polymers, shedding light on the impact of the core employed in MSPs. Additionally, it examines the influence of parameters such as solvent choice and counter-ions on the supramolecular assemblies. The ability of these materials to adapt their properties in response to changing environmental conditions challenges the traditional goal of creating stable materials, marking a paradigm shift in material design.

Biogenic Polymer-Based Fluorescent Assemblies: Versatile Platforms for Ultrasensitive ATP Detection and Enzyme Assay.

Here, we investigated the optical properties of biocompatible supramolecular assemblies formed through electrostatic interactions between anionic fluorescent dyes and biogenic polymers. The dynamic equilibrium between the monomeric form (fluorescent) and aggregates (nonfluorescent) of dye molecules is responsible for the stimuli-responsive behavior of these polymer composites, which can respond to changes in pH, temperature, and ionic strength. Furthermore, we employed supramolecular assemblies for the purpose of turn-on fluorescence sensing of adenosine triphosphate (ATP) at physiological pH. Notably, no interference was observed even in the presence of well-known competing analytes such as pyrophosphate. In addition to its outstanding selectivity, the present system can detect ATP at concentrations as low as 4.8 nM. The superior detection capabilities are achieved through multiple interactions with biogenic polymers, involving the adenine ring, ribose unit (through hydrogen bonding), and phosphate groups (via charge pairing) of ATP. Given the remarkable sensitivity to ATP, we have applied the present system for the detection of a dephosphorylating enzyme, alkaline phosphatase.

Molecular design of a solvent-free spiropyran-containing DNA material with triple external stimuli-responsive behavior

External stimuli-responsive behavior allows smart materials to gain controllable physicochemical changes. Compared to single stimulus response, the multiple stimuli-responsive behavior makes materials suitable for accommodating different environments, which is highly desired but appreciably more difficult to be addressed. In this study, a spiropyran-containing ammonium surfactant SPA is designed and synthesized for the electrostatic complexation with DNA, affording the ionic biomaterial DNA-SPA with a triple stimuli-responsive behavior. The treatments of UV irradiation and heating can promote fast ring-opening isomerization of DNA-SPA by giving distinct orange-to-purple color change. These properties make DNA-SPA a good candidate biomaterial for information recording and temperature indication. DNA-SPA also responds to humidity by showing linear fit between absorption intensity and relative humidity, providing the potential use as a hygrometer. The half-life of the ring-opening isomer of DNA-SPA favors the stable indications of UV irradition, temperature and humidity, and the sensitivity of ring-opening isomer to Vis light promotes the recyclable use of such biomaterial. This study provides a designing strategy for the fabrication of multiple external stimuli-responsive functional materials, opening a new pathway for gaining smart biomaterials capable of working in various fields.

PNIPAm-Based pH and Thermoresponsive Copolymer Hydrogel for Hydrophobic and Hydrophilic Drug Delivery.

The regulated and targeted administration of hydrophobic and hydrophilic drugs is both promising and challenging in the field of drug delivery. Developing a hydrogel which is responsive to dual stimuli is considered a promising and exciting research area of study. In this work, melamine functionalized poly-N-isopropyl acrylamide-co-glycidyl methacrylate copolymer has been developed by copolymerizing glycidyl methacrylate (GMA) monomer with N-isopropyl acrylamide (NIPAm) and further functionalized with melamine units (pNIPAm-co-pGMA-Mela). The prepared pNIPAm-co-pGMA-Mela copolymer hydrogel was characterized using various characterization techniques, including 1H NMR, FTIR, SEM, zeta potential, and particle size analysis. A hydrophobic drug (ibuprofen, Ibu) and hydrophilic drug (5-fluorouracil, 5-Fu) were selected as model drugs. Dual pH and temperature stimuli-responsive drug release behavior of the pNIPAm-co-pGMA-Mela hydrogel was evaluated under different pH (pH 7.4 and 4.0) and temperature (25 °C, 37 °C, and 45 °C) conditions. Furthermore, the in vitro biocompatibility of the developed pNIPAm-co-pGMA-Mela copolymer hydrogel was determined on MDA-MB-231 cells. The pH and temperature-responsive drug delivery study results reveal that the pNIPAm-co-pGMA-Mela hydrogel system is responsive to both pH and temperature stimuli and exhibits about ~100% of Ibu and 5-Fu, respectively, released at pH 4.0/45 °C. Moreover, the MTT assay and hemocompatibility analysis results proved that the pNIPAm-co-pGMA-Mela hydrogel system is biocompatible and hemocompatible, suggesting that that it could be used for drug delivery applications. The experimental results suggest that the proposed pNIPAm-co-pGMA-Mela hydrogel system is responsive to dual pH and temperature stimuli, and could be a promising drug carrier system for both hydrophilic and hydrophobic drug delivery applications.

Acid and Glutathione Dual-Responsive, Injectable and Self-Healing Hydrogels for Controlled Drug Delivery.

Considering the complexity of physiological microenvironments and the risks of surgical infection, there still remains critical demand to develop a hydrogel as a drug release platform with multifunctional properties, including good neutral stability and sensitive multiple stimuli-responsive behaviors, as well as injectable and self-healing properties. Herein, we present a facile preparation of injectable, self-healing hydrogels with acid and glutathione (GSH) dual-responsiveness for controlled drug delivery. Initially, the anticancer drug camptothecin (CPT) was premodified with disulfide bonds and attached to poly(ethylenimine) (PEI) via the Schiff base reaction, resulting in PEI-CPT. Subsequently, OSA-IR780 was synthesized through the Schiff base reaction involving IR780 with amine groups (IR780-NH2) and oxidized sodium alginate with aldehyde groups (OSA). The formation of PEI-CPT/OSA-IR780 hydrogels with various solid contents occurred rapidly within 40 s through a simple mixing process of the aqueous solution of PEI-CPT and OSA-IR780. These hydrogels exhibited remarkable stability under neutral conditions and controlled release of CPT upon exposure to simulated tumor environments characterized by acidic conditions and elevated GSH concentrations. Furthermore, they had significant injectable and self-healing properties due to the dynamically imine-cross-linked networks. In addition, the prepared hydrogels exhibited long-term biodegradability and biocompatibility. Collectively, these features indicate the great potential of PEI-CPT/OSA-IR780 hydrogels as therapeutic delivery vehicles.

Multiresponsive Core-Shell Microgels Functionalized by Nitrilotriacetic Acid.

Stimuli-responsive microgels with ionizable functional groups offer versatile applications, e.g., by the uptake of oppositely charged metal ions or guest molecules such as drugs, dyes, or proteins. Furthermore, the incorporation of carboxylic groups enhances mucoadhesive properties, crucial for various drug delivery applications. In this work, we successfully synthesized poly{N-vinylcaprolactam-2,2'-[(5-acrylamido-1-carboxypentyl)azanediyl]diacetic acid} [p(VCL/NTAaa)] microgels containing varying amounts of nitrilotriacetic acid (NTA) using precipitation polymerization. We performed fundamental characterization by infrared (IR) spectroscopy and dynamic and electrophoretic light scattering. Despite their potential multiresponsiveness, prior studies on NTA-functionalized microgels lack in-depth analysis of their stimuli-responsive behavior. This work addresses this gap by assessing the microgel responsiveness to temperature, ionic strength, and pH. Morphological investigations were performed via NMR relaxometry, nanoscale imaging (AFM and SEM), and reaction calorimetry. Finally, we explored the potential application of the microgels by conducting cytocompatibility experiments and demonstrating the immobilization of the model protein cytochromec in the microgels.

Controlling A x Mn[Fe(CN)6] charge transfer pathways through tilt-engineering for enhanced metal-to-metal interactions.

The induction of structural distortion in a controlled manner through tilt engineering has emerged as a potent method to finely tune the physical characteristics of Prussian blue analogues. Notably, this distortion can be chemically induced by filling their pores with cations that can interact with the cyanide ligands. With this objective in mind, we optimized the synthetic protocol to produce the stimuli-responsive Prussian blue analogue A x Mn[Fe(CN)6] with A = K+, Rb+, and Cs+, to tune its stimuli-responsive behavior by exchanging the cation inside pores. Our crystallographic analyses reveal that the smaller the cation, the more pronounced the structural distortion, with a notable 20-degree Fe-CN tilting when filling the cavities with K+, 10 degrees with Rb+, and 2 degrees with Cs+. Moreover, this controlled distortion offers a means to switch on/off its stimuli-responsive behavior, while modifying its magnetic response. Thereby empowering the manipulation of the PBA's physical properties through cationic exchange.

Multi-stimuli-responsive behaviours of fluorenone-based donor–acceptor–donor triads in solution and supramolecular gel states

The newly developed fluorenone-based donor–acceptor–donor triads formed supramolecular organogels in appropriate solvents. The stimuli-responsive behaviours in solution as well as in supramolecular gels of the fluorenone derivatives were clarified.

Photoswitchable coordination cages.

Stimuli-responsive behaviour is key to the design of smart materials, surfaces, nano-systems and effector molecules, allowing their application as switchable catalysts, molecular transporters, bioimaging probes or caged drugs. Supramolecular chemistry has embraced the widespread integration of photoswitches because of their precise spatiotemporal addressability and waste-free nature. In the vibrant area of discrete metal-mediated self-assembly, however, photoswitches are still rarely employed. Only recently has it been shown that embedding photoswitches into the organic backbones of coordination cages enables control of their host and material properties and thus unlocks the hitherto unexploited dynamic adaptivity of such systems. Here we discuss four cases where triggering ligand-integrated photoswitches leads to (1) control over disassembly/reassembly, (2) bi-stable switching between defined states, (3) interplay with thermal processes in metastable systems and (4) light-fuelled dissipative self-assembly. We highlight first clues concerning the relationship between fundamental photophysics and dynamic assembly equilibria and propose directions for future development.

Exploring microgel adsorption: synthesis, classification, and pollutant removal dynamics.

Microgels have gained significant importance for the removal of pollutants owing to their stimulus-responsive behavior, high stability, and reusable capacity. However, despite these advantages, several hurdles need to be overcome to fully maximize their potential as effective adsorbents for eradicating various contaminants from the environment, such as metallic cations, organic compounds, anions, harmful gases, and dyes. Therefore, a critical review on the adsorption of pollutants by microgels is needed. In this regard, this review presents the latest developments in the adsorptive properties of microgels. The synthetic methods, architectural structures, and stimulus-responsive behavior of microgels are explained in detail. In addition, this review explores various factors that directly influence the adsorption of pollutants by microgels, such as pH, feed composition, content of pollutants, content of comonomers, agitation time, temperature, microgel dose, nature of both adsorbates (pollutants) and adsorbents (microgels), nature of the medium, and ionic strength. Various adsorption isotherms are also explored together with the kinetic aspects of the adsorption process to provide a comprehensive understanding.

Therapeutic coordination polymers: tailoring drug release through metal-ligand interactions.

Developing tunable materials which exhibit sustained drug release is a considerable challenge. Herein, we report the concept of Therapeutic Coordination Polymers (TCPs); non-porous coordination polymers constructed from biocompatible components which demonstrate tunable zero-order drug release kinetics upon degradation of metal-ligand bonds. TCPs were constructed from three principal components: (i) a cationic metal center (M = Mg2+, Mn2+, Zn2+, or Cu2+); (ii) an anionic drug (Diclofenac); and (iii) an alkyl bis-imidazole organic ligand which behaves as a "linker" between metal centers. Most drug-release materials, such as amorphous polymer dispersions, or metal-organic frameworks rely on a diffusion-based mechanism for drug release, but the degradation-controlled release of drugs from non-porous one-periodic coordination polymers has been largely unexplored. TCPs described herein exhibit a high wt% of pharmaceutical (>62%), tailorable zero-order drug release rate kinetics which span over three orders of magnitude, and stimuli-responsive drug release behavior making them well suited for extended drug-release applications.

Stimuli-responsive spin crossover behavior in 3D Fe(ii) porous coordination polymers for guest molecules

A new 3D FeII spin crossover porous coordination polymer, [Fe(tpe)2dca]ClO4·5CHCl3·3CH3OH which accommodates guest molecules in its cavities to modulate its magnetic and optical properties, was prepared and investigated in detail.

Design of multi-responsive and actuating microgels toward on-demand drug release.

Multifunctional colloidal microgels that exhibit stimuli-responsive behaviour and excellent biocompatibility have attracted particular attention for developing functional compartmentalized networks. Herein, a series of stimuli-responsive microgels (M0, M1, and M2) were designed through the copolymerization of di(ethylene glycol) methyl ether methacrylate (DEGMA) and methacrylic acid (MAA) monomers using hydroxy ethyl methacrylate-coupled azobenzene (HEMA-Az) and ethylene glycol dimetharylate (EGDMA) as crosslinkers. The behaviour of the microgels in response to temperature, pH, and light was thoroughly investigated using spectroscopic, microscopic, and light-scattering techniques. Interestingly, the microgels deswelled with an increase in temperature, decrease in pH, and under the irradiation of UV light. Such a reversible swelling/deswelling behaviour was exploited for microgel M2, which showed better photoactuation at pH 5 with a higher fluid pumping velocity. The actuating microgel M2 was optimized for loading the drug ciprofloxacin (Cf) to study its release at different temperature, pH, and light conditions. Microgel M2 exhibited photoresponsive Cf release at pH 5 and 37 °C, demonstrating its potential for application in on-demand drug release.

Nanogel-based composites for bacterial antibiofilm activity: advances, challenges, and prospects.

Nano-based approaches, particularly nanogels, have recently emerged as a potential strategy for combating biofilm-related infections. Their exceptional characteristics including biocompatibility, biodegradability, stability, high water content, stimuli-responsiveness, and their nano size (which enables their penetration into biofilms) make nanogels a promising technology in the biomedical field. However, exploring nanogels for biofilm treatment remains in its early stages. This review examined the status of nanogels application for the treatment of bacterial biofilms. Recent investigations studied nanogels derived from natural polymers like chitosan (CS), hyaluronic acid (HA), and alginate, among others, for eliminating and inhibiting biofilms. These nanogels were utilized as carriers for diverse antibiofilm agents, encompassing antibiotics, antimicrobial peptides, natural extracts, and nanoparticles. Utilizing mechanisms like conventional antibody-mediated pathways, photodynamic therapy, photothermal therapy, chemodynamic therapy, and EPS degradation, these nanogels effectively administered antibiofilm drugs, exhibiting efficacy across several bacterial strains, notably Staphylococcus aureus (S. aureus), Pseudomonas aeruginosa (P. aeruginosa), and Escherichia coli (E. coli), among others. Despite showing promise, nanogels remain relatively underexplored in biofilm treatment. This review concludes that research gaps are still present in biofilm treatment processes including (i) a better understanding of the stimuli-responsive behaviors of nanogels, (ii) active targeting strategies, and (iii) the narrow spectrum of antibiofilm agents loaded into nanogels. Hence, future studies could be directed towards the following elements: the exploration of multi-strain biofilms rather than single-strain biofilms, other endogenous and exogenous stimuli to trigger drug release, active targeting mechanisms, a broader range of antibiofilm agents when employing nanogels, and fostering more comprehensive and reliable biofilm treatment strategies. This review found that there are currently several research gaps as well in the use of nanogels for biofilm therapy, and these include: (i) very limited exogenous and endogenous stimuli were explored to trigger drug release from nanogels, (ii) the active targeting strategies were not explored, (iii) a very narrow spectrum of antibiofilm agents was loaded into nanogels, and (iv) only biofilms of single strains were investigated.