Search Results (656)

The emergence of biological membranes was a critical step in the origin of cellular life because compartmentalization enabled molecular concentration, selective interactions, and increasingly complex chemical evolution. While fatty acids are widely considered the primary constituents of primitive membranes, the origin of the hydrophilic molecular scaffolds required for more stable amphiphilic systems remains unresolved. In this review, we propose a new conceptual framework in which low-molecular-weight polyols—including ethylene glycol, glycerol, tetritols, and related sugar alcohols—served as key molecular intermediates linking abiotic carbohydrate chemistry with the emergence of proto-lipids and protomembranes during a pre-phosphate stage of Earth history. Experimental and theoretical studies indicate that abiotic carbon chemistry can generate abundant polyols capable of esterification, etherification, hydrogen bonding, and reversible complexation with borate species. We hypothesize that borate-mediated stabilization of sugars and polyols promoted molecular selection, while sulfur-rich geochemical environments supplied chemically diverse amphiphiles and redox-active reaction networks. Building upon these observations, we propose a pH-dependent evolutionary model in which acidic sulfur-rich environments favored sulfo-protolipids, near-neutral environments promoted mixed polyol–fatty acid membranes, and alkaline boron-rich systems facilitated borate-associated amphiphiles and dynamic supramolecular membrane organization. We further suggest that borate-cross-linked polyol hydrogels acted as transitional soft-matter systems connecting molecular synthesis, membrane self-assembly, compartmentalization, and the emergence of proto-informational assemblies. Modern glycolipids, sulfolipids, archaeal ether lipids, and calditol-containing tetraether membranes are discussed as structural analogues, rather than direct evolutionary descendants, supporting the chemical versatility of polyol-based membrane architectures. Although the proposed evolutionary framework remains hypothetical, it integrates current knowledge from prebiotic organic chemistry, membrane biophysics, boron coordination chemistry, sulfur geochemistry, and systems chemistry into a unified and experimentally testable model for the evolution of proto-lipids, protomembranes, and early protocellular organization. Full article

Deep eutectic systems (DESs) have evolved from sustainable solvent alternatives to promising bioactive platforms with reported antimicrobial, anti-inflammatory, regenerative, cryoprotective, and cytoprotective properties. However, despite the growing number of biological studies, the mechanistic basis of these effects remains poorly understood because biological activity is still interpreted predominantly from the chemical identity of the hydrogen-bond donor and acceptor, rather than from the supramolecular organization of the eutectic system itself. This review is intended to provide anyone interested in the biomedical and pharmaceutical applications of DESs with a conceptual framework for understanding how supramolecular organization may influence the biological performance of DES-based systems, without requiring extensive expertise in physical chemistry. It critically analyzes the current evidence linking DES structure with biological function. The literature reveals that many reported biological responses cannot be fully explained by the properties of the individual constituents alone, supporting the existence of emergent physicochemical behavior associated with eutectic formation. Current evidence further demonstrates that DESs are dynamic supramolecular systems characterized by hydrogen-bond networks, nanoscale heterogeneity, hydration-dependent structural rearrangement, and persistent local organization under biologically relevant conditions. These structural features generate localized physicochemical microenvironments capable of modulating membrane organization, protein hydration, osmotic balance, and biomolecular interactions, providing a plausible mechanistic basis for the diverse biological effects reported to date. Our analysis also highlights a fundamental disconnect between the extensive physicochemical characterization of DESs and the predominantly composition-based interpretation of their biological activity. While conventional Quantitative Structure–Activity Relationship (QSAR) approaches rely on molecular descriptors of individual components, they fail to capture the higher levels of organization that characterize these dynamic multicomponent systems. Based on concepts established in supramolecular chemistry, self-assembled biomaterials, colloidal science, and soft matter, we propose a Hierarchical Structure–Activity Relationship (H-SAR) framework in which biological activity emerges from successive levels of organization extending from molecular composition and hydrogen-bond networks to nanostructural organization, hydration-dependent restructuring, localized physicochemical microenvironments, and biological interfaces. This framework provides a mechanistic basis for interpreting DES bioactivity and could offer a conceptual roadmap for the rational design, predictive modeling, and biomedical translation of next-generation bioactive deep eutectic systems. Full article

Hemodialysis (HD) remains the most widely adopted renal replacement therapy for patients with end-stage kidney disease; however, its delivery entails a substantial environmental burden due to high water and energy consumption and extensive reliance on single-use synthetic polymeric membranes. As the global prevalence of chronic kidney disease increases, the ecological footprint of dialysis systems has become a critical challenge for sustainable healthcare. Conventional HD membranes, based on petroleum-derived polymers, provide controlled permeability but are inherently non-renewable, non-biodegradable, and susceptible to fouling and bio-incompatibility, underscoring the need for alternative, more sustainable materials. Chitosan has emerged as a promising biopolymer owing to its biodegradability, intrinsic antimicrobial activity, chemical versatility, and favorable hemocompatibility. This review presents a comprehensive analysis of chitosan-based hybrid membranes for HD, with emphasis on sustainability-driven material innovation. The structural chemistry and functional properties of chitosan are discussed in relation to molecular weight, degree of deacetylation, and supramolecular organization, followed by a comparative assessment of chitosan derived from crustacean, insect, fungal, and cephalopod sources. Attention is given to fungal chitosan as a naturally deacetylated, high-purity, and reproducible biomaterial aligned with circular bioeconomy principles. Eco-innovative extraction and purification strategies, including enzymatic and low-energy processes, are critically examined alongside membrane fabrication approaches such as polymer blending, electrospinning of hollow fibers, and functionalization strategies aimed at improving hemocompatibility, antimicrobial performance, and fouling resistance. Key challenges related to membrane reuse, scale-up, regulatory compliance, and clinical translation are also addressed. Overall, this review highlights fungal-derived chitosan as a sustainable platform for next-generation HD membranes. Full article

Breast cancer treatment still faces challenges including local recurrence, systemic toxicity, tumor heterogeneity, drug resistance, and immunosuppression. Conventional systemic administration provides limited exposure at the tumor site and exhibits significant toxicity. Injectable hydrogels, combining the properties of minimally invasive administration, in situ gelation, local retention, and sustained release, have become a key platform for local precision drug delivery. Compared with nanomedicines or free drugs, hydrogels can both prolong drug retention time and achieve on-demand release through the modulation of crosslinking density, degradation rate, and responsive chemical bonds. This review is organized around the material logic of such systems. Injectable hydrogels are first classified into natural, synthetic, hybrid, supramolecular, nanocomposite, and self-healing systems, the in situ gelation chemistries available to each are compared, and network parameters such as crosslinking density, mesh size, swelling, porosity, modulus, and rheology are related to release kinetics and intratumoral retention. Current research is primarily advancing along two directions: one is the construction of pH-, enzyme-, redox/ROS-, hypoxia-, ATP-, glucose-or thermo-responsive hydrogels; the other is achieving active targeting by integrating functionalized hydrogels with targets such as CD44, folate receptor, integrins, EGFR, transferrin receptor, and HER2 or with biomimetic cell-membrane coatings. On this basis, hydrogels have been extended to cancer vaccines, immune checkpoint modulation, local delivery of CAR-T/CAR-NK, as well as combination therapies involving chemotherapy, photothermal therapy, photodynamic therapy, chemodynamic therapy, sonodynamic therapy, radiosensitization, gene therapy, and theranostics. The constraints imposed on hydrogel design by different payload classes, including small molecules, natural products, proteins and peptides, nucleic acids, antibodies, exosomes, and gene-editing machinery, are further examined, and imaging-integrated theranostic gels are discussed together with the emerging role of machine learning and digital fabrication in hydrogel optimization. Based on the biological foundations of breast cancer, this review summarizes advances in the material design, microenvironment-responsive release, targeting strategies, immunomodulation, and combination therapy of hydrogels, critically evaluates the limitations of each strategy, and aims to provide a reference for the design of mechanistically well-defined and translatable hydrogel delivery systems for breast cancer. Full article

Protein aggregation strongly depends on the local environment, yet investigating it in compartmentalized, high-surface-area volumes remains challenging. Here, we present an optically controlled platform for inducing and monitoring protein aggregation in microliter droplets. Local pH changes are generated in situ via photoconversion of 2-nitrobenzaldehyde, enabling noninvasive environmental control without mechanical mixing or direct perturbation of the sample. By combining fluorescein-based pH measurements with Raster Image Correlation Spectroscopy (RICS), pH variations and protein diffusion were monitored. As a model system, we investigated β-lactoglobulin, whose association state strongly depends on pH. Light-induced acidification progressively shifted the protein toward its isoelectric region, resulting in a measurable decrease in the diffusion coefficient consistent with the formation of larger supramolecular species. Furthermore, modulation of electrostatic interactions through NaCl addition revealed the sensitivity of the system to environmental factors governing the balance between electrostatic repulsion and short-range attractive interactions. Under these conditions, the platform enabled the observation of aggregation behaviors that were significantly less pronounced in corresponding bulk conditions. Overall, this droplet-based approach allows for the precise manipulation of local chemistry and quantitative analysis of biomolecular self-assembly, making it readily extendable to various noninvasive, time-resolved monitoring applications. Full article

Supramolecular hydrogels are usually prepared in aqueous media containing diverse ions, for instance, buffer solutions, yet the influences of ions, especially the Hofmeister effect, on their self-assembly are often overlooked. Here, we systematically investigate the impacts of different anions in the Hofmeister series on the self-assembly of supramolecular hydrogels. On the basis of a hydrazone formation-mediated supramolecular gelation system, we found that the addition of kosmotropic anions can accelerate the self-assembly of gelators as determined by rheology and critical gelation concentration tests. Confocal microscopy observations and rheological measurements demonstrate that the resultant hydrogels have denser fibrous networks and higher stiffness relative to the samples without additional kosmotropic anions. In contrast, chaotropic anions effectively impede the self-assembly process. These impacts of ions on the self-assembly of supramolecular hydrogels are in line with the specific ion effect. This work suggests that the Hofmeister effect can serve as an effective approach to control the self-assembly and the properties of supramolecular hydrogels, and the effects of ions should be considered in the studies of supramolecular hydrogels. Full article

Cardiolipin (CL), a dimeric phospholipid with four acyl chains and a small polar head group, is one of the most striking examples of evolutionary continuity in cell biology. Present in the plasma membrane of α-proteobacteria and retained without fundamental modification in the inner mitochondrial membrane (IMM) of every eukaryote examined, CL has persisted across roughly two billion years of evolution, a period over which the mitochondrion shed the great majority of its ancestral genes. This review develops, as an organizing hypothesis rather than an established fact, the proposal that CL acts as a programmable signaling hub: a lipid whose physical chemistry and membrane address allow it to nucleate distinct supramolecular platforms in response to discrete stress signals, each platform coupling a specific mitochondrial state to a defined cell fate outcome. Three CL-dependent platforms are examined, together with a fourth, emerging axis, and the evidence supporting each is explicitly graded. Platform 1, the catalytic peroxidase platform, converts the constitutive CL–cytochrome c (cyt c) structural complex into an enzymatic reaction under oxidative stress, generating oxidized CL (oxCL) species that contribute to cyt c release from the IMM; this platform is the best supported of the four. Platform 2, the receptor-like mitophagy platform, exploits NME4-dependent CL scramblase activity to translocate CL from the IMM to the outer mitochondrial membrane (OMM) surface upon membrane potential dissipation, creating an externalized “eat-me” signal recognized by LC3-II; the evidence here is moderate and largely cell-based. Platform 3, the caspase-8/BID activation platform, is proposed to assemble a CL microdomain scaffold at the OMM that recruits caspase-8, markedly accelerates BID cleavage, and couple extrinsic apoptotic signals to mitochondrial outer membrane permeabilization (MOMP); this model rests substantially on reconstituted systems and requires further validation in intact cells and in vivo. A fourth, still-debated axis links CL externalization to innate immune activation through NLRP3 recruitment, for which alternative membrane-recruitment models exist. The argument advanced here is that the conservation of CL is unlikely to be explained by its structural roles alone, although those roles are themselves sufficient to impose strong selection; disentangling structural from signaling contributions remains an open problem, and the comparative genomic work needed to do so has not yet been performed. Full article

Cyclodextrin (CD)-based supramolecular nanofibers (NFs) have emerged as an advanced class of multifunctional materials for active food packaging by integrating host–guest supramolecular chemistry with electrospun nanofibrous architectures. The unique hydrophobic cavity and hydrophilic exterior of CDs enable the encapsulation of a wide range of bioactive compounds, including essential oils, natural antioxidants, antimicrobials, and volatile active agents, thereby enhancing their solubility, stability, controlled release, and preservation efficacy. This review comprehensively discusses the molecular structure and inclusion complexation mechanisms of CDs, recent advances in polymer-assisted and polymer-free electrospinning strategies, and the design of CD-based supramolecular nanofibers for food preservation. Particular emphasis is placed on the relationship between fiber morphology, supramolecular interactions, and controlled release behavior, which collectively govern antimicrobial, antioxidant, moisture management, and barrier properties. Recent developments involving biodegradable polymers, hybrid nanofibrous systems, and cyclodextrin-based metal–organic frameworks (CD-MOFs) are critically summarized, highlighting their roles in improving encapsulation efficiency, mechanical stability, and multifunctional performance. The review further compares CD-based nanofibers with other advanced encapsulation technologies, including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, polymeric nanoparticles, microspheres, and conventional MOFs, providing a comprehensive evaluation of their loading capacity, release kinetics, scalability, cost, and regulatory suitability for food-contact applications. Representative applications in the preservation of fruits, vegetables, meat, seafood, dairy products, and bakery products demonstrate significant improvements in microbial inhibition, oxidation resistance, ethylene and volatile organic compound adsorption, and shelf-life extension through sustained delivery of natural preservatives. Ultimately, the current challenges, including large-scale manufacturing, long-term stability, regulatory approval, and commercialization, are discussed together with future directions, focusing on smart packaging, stimuli-responsive delivery systems, intelligent sensing, biodegradable multifunctional materials, and sustainable industrial implementation. Full article

Gallium (Ga)-based liquid metal (LM) composites, particularly those based on eutectic gallium–indium (EGaIn) and related alloys, have emerged as a promising materials platform for soft and deformable energy storage owing to their unique combination of metallic conductivity, fluidic deformability, and adaptive interfaces. Despite rapid advances in LM-enabled devices, binders remain insufficiently understood and are still commonly regarded as passive structural components. Here, we present a comprehensive binder-centered perspective for LM composites, establishing the binder as a key regulator of electro-chemo-mechanical coupling, interfacial stability, transport behavior, and processability in soft energy systems. We show that tailored binder chemistries in Ga-based LM systems—including stretchable batteries, printable conductors, and soft electrochemical devices—govern LM droplet dispersion, suppress coalescence and leakage, and preserve conductive percolation under large deformation, while enabling room-temperature fabrication and printability through rheological regulation and interfacial wetting. Beyond mechanical confinement, emerging binder functionalities—including dynamic bonding, supramolecular interactions, ionically conductive networks, and reversible polymer architectures—enable self-healing interfaces, adaptive transport pathways, and robust adhesion in deformable devices. By integrating recent advances in stretchable batteries, flexible supercapacitors, printable electronics, and multifunctional soft energy systems, we establish a unified multiscale framework linking binder molecular design to device-level electrochemical and mechanical performance. We further discuss sustainability and manufacturing considerations, including recyclable polymer networks, low-temperature fabrication, and scalable processing strategies. Finally, we outline current challenges and future opportunities toward programmable binder systems with tunable viscoelasticity, interfacial reactivity, and adaptive functionality. This Review establishes binder-centered engineering as a key pathway for transforming LM composites from proof-of-concept materials into resilient, manufacturable, and multifunctional soft energy technologies for wearable, stretchable, and biointegrated electronics. Full article

The nucleophilic properties of the isolated dicyanoaurate(I) anion in σ-hole interactions were investigated using theoretical calculations of models from 19 crystalline literature structures. The study focuses on the ability of [Au(CN)₂]⁻ to participate in various noncovalent interactions, including halogen, chalcogen, pnictogen, and tetrel bonds. The research reveals that both nitrogen atoms of the cyanide ligands and the gold(I) center exhibit nucleophilic behavior. The nature of all interactions and philicities of interacting atoms were confirmed using a set of theoretical methods, including QTAIM topological analysis, noncovalent interaction plots (NCIplot), electrostatic potential (ESP) surfaces, electron localization function (ELF), analysis of electron density (ED), and electrostatic potential (ESP) minima in their 1D profiles along the bond paths, BSSE corrected dimerization energies, and NBO charge-transfer analysis. The study demonstrates that the dicyanoaurate(I) anion can act as a versatile building block in supramolecular chemistry, participating in multiple types of noncovalent interactions through different sites, including first confirmed examples of gold(I)-involving intermolecular chalcogen bonds. Full article

Curcuminoids from Curcuma longa L. (curcumin, demethoxycurcumin, bisdemethoxycurcumin) are attractive bioactives yet constrained by low water solubility and chemical instability. Herein, we introduce a Supramolecular Deep Eutectic Solvent (SupraDES) as a “Janus” green platform, combining extraction and stabilization with a subsequent solvent-to-material strategy. Eight NaDES/SupraDES formulations based on choline chloride (ChCl) or betaine with glycerol (Gly) or citric acid (CitA), with/without β-cyclodextrin (βCD), were assessed. The extinction coefficients of the most promising solvents were extrapolated at 425 nm for the UV–vis quantification of curcuminoids, to determine extraction performance. The SupraDES ChCl:Gly:βCD gave the best performance during the first solvent screening, improving at the same time the bioactive stability (after 30-day, 47.5% loss vs. 62.8% of ChCl:Gly alone). Subsequent microwave-assisted extraction (MAE) optimization identified 80 °C as the optimal process temperature, with near-equilibrium reached within 15 min (3139.4 µgCurc/gEXT). Peleg modelling (R² = 0.997) indicated a fast extraction rate and limited benefit from longer residence times. Finally, the curcuminoid-loaded SupraDES was incorporated into polyvinyl alcohol (PVA) networks crosslinked with CitA and 2,5-bis(hydroxymethyl)furan (BHMF); thermal analysis confirmed the formation of a stable crosslinked structure. To the best of our knowledge, this is the first report of a βCD-based SupraDES acting as a Janus platform that couples supramolecular extraction of lipophilic bioactives with their direct incorporation into bio-based polymeric materials, exemplifying an integrated green chemistry approach aligned with circular bioeconomy principles. Full article

Skin aging is a central focus of skin health. Supramolecular chemistry has emerged as a powerful strategy for enhancing the performance of cosmetic active ingredients. Adenosine is a promising anti-aging ingredient in skincare products, but its cosmetic application is limited by poor water solubility and low skin penetration. This study developed a supramolecular complex combining adenosine with ectoine through cocrystallization. The supramolecular assembly was characterized by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR) and density functional theory (DFT) calculations revealed extensive hydrogen-bonding networks between the components. The optimal supramolecular composition (1:1.5 molar ratio) achieved a 5.5-fold increase in water solubility. The supramolecular organization enhanced skin permeability by 3.1-fold in ex vivo porcine skin models. In fibroblast cell models, the supramolecular system exhibited superior antioxidant activity with 30.3% greater reactive oxygen species (ROS) reduction and restored cellular adenosine triphosphate (ATP) levels by 2.1-fold under H₂O₂-induced oxidative stress compared to individual components. These findings demonstrate that the adenosine–ectoine supramolecular complex represents an innovative multifunctional ingredient for basic anti-aging cosmetics, offering enhanced delivery, improved safety, and superior biological efficacy through supramolecular engineering. Full article

The development of supramolecular materials has opened up unprecedented opportunities for smart, responsive systems. Yet, their practical application in extreme environments—deep space, deep sea, polar regions, high-temperature and high-pressure reservoirs—is fundamentally challenged by the inherent trade-off between structural stability and dynamic adaptability. This review addresses this core issue by presenting a comprehensive framework for understanding and overcoming the stability–dynamism mismatch under harsh condition. We systematically analyze the molecular mechanisms by which severe factors disrupt non-covalent networks. Based on these insights, we outline four universal molecular design strategies that re-establish the balance, and summarize engineering applications across aerospace, marine, energy, and polar exploration. Beyond offering a comprehensive roadmap for rational material design, this review highlights persistent challenges—including multi-field coupling failure mechanisms, industrialization barriers, and the limitations of current systems—and outlines future directions. By bridging fundamental chemistry with extreme environment engineering, this work aims to guide the next generation of supramolecular materials that can reliably serve in the most demanding operational scenarios. Full article

Synthesis of bifunctional cytisine–squaramide derivatives bearing a single amino acid moiety has revealed an unexpected and intriguing chemical challenge. During modification of cytisine squaramates with α-amino acids, base-sensitive amido esters readily underwent hydrolysis, forming poorly soluble amido-acid side products that resisted standard purification and initially obscured their identity. Persistent observation of these elusive precipitates prompted a deliberate co-crystallization approach, which unambiguously revealed their supramolecular nature using single-crystal X-ray diffraction. With this insight, optimized purification strategies allowed isolation of analytically pure Cyt-SQ-OH and its derivatives, which were characterized by complementary spectroscopic techniques, X-ray crystallography and computational studies. Furthermore, the DFT-optimized parameters of all compounds were determined, providing additional insight into their structural and electronic properties. This work highlights the interplay between reactivity, solubility, and supramolecular assembly in cytisine–squaramide-amino acid hybrids, providing a robust platform for future exploration of multifunctional conjugates with potential applications in medicinal chemistry, molecular recognition, and materials science. Full article

Self-healing materials have attracted increasing attention as a strategy to enhance durability, extend service life, and reduce maintenance in advanced material systems. Among these, cellulose-based self-healing materials represent a sophisticated intersection between sustainable macromolecular chemistry and adaptive materials science. This review provides a synthesis of recent advancements in the field, systematically categorizing materials derived from cellulose raw materials. We evaluate the fundamental chemical strategies employed to achieve autonomous repair, distinguishing between extrinsic mechanisms—utilizing cellulose-based micro/nano-capsules to sequester healing agents—and intrinsic mechanisms governed by dynamic covalent chemistry (Schiff-base, boronic ester, Diels–Alder) and supramolecular interactions (hydrogen bonding, metal–ligand coordination, and host–guest assemblies). The analysis highlights how cellulose’s hierarchical structure and abundant surface functionality are leveraged to overcome the traditional trade-off between mechanical toughness and healing efficiency. Particular emphasis is placed on the transition from simple structural hydrogels to sophisticated multifunctional systems. These include ultra-stretchable strain and pressure sensors for e-skin applications, biocompatible and injectable matrices for chronic wound management and stem cell delivery, and advanced anti-freezing eutectogels for performance in extreme environments. Furthermore, we explore the integration of cellulose into traditional sectors, such as self-healing concrete utilizing microbe-induced calcification and smart, eco-friendly coatings for corrosion protection. Finally, we discuss critical challenges, including environmental stability, scalability, and the development of standardized evaluation protocols, providing a roadmap for the next generation of bio-derived, sustainable and intelligent materials. Full article