Long-Term Prevention of Biofilm Formation by Polycatechol-Based Supramolecular Assemblies with Low Molecular Weight Polymers on Surfaces.

Achievement of a stable surface coating with long-term resistance to biofilm formation remains a challenge. Catechol-based polymerization chemistry and surface deposition are used as tools for surface modification of diverse materials. However, the control of surface deposition of the coating, surface coverage, coating properties, and long-term protection against biofilm formation remain to be solved. We report a new approach based on supramolecular assembly to generate long-acting antibiofilm coating. Here, we utilized catechol chemistry in combination with low molecular weight amphiphilic polymers for the generation of such coatings. Screening studies with diverse low molecular weight (LMW) polymers and different catechols are utilized to identify lead compositions, which resulted in a thick coating with high surface coverage, smoothness, and antibiofilm activity. We have identified that small supramolecular assemblies (∼10 nm) formed from a combination of polydopamine and LMW poly(N-vinyl caprolactam) (PVCL) resulted in relatively thick coating (∼300 nm) with excellent surface coverage in comparison to other polymers and catechol combinations. The coating properties, such as thickness (10-300 nm) and surface hydrophilicity (with water contact angle: 20-60°), are readily controlled. The optimal coating composition showed excellent antibiofilm properties with long-term (>28 days) antibiofilm activity against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) strains. We further utilized the combination of optimal binary coating with silver to generate a coating with sustained release of silver ions, resulting in killing both adhered and planktonic bacteria and preventing long-term surface bacterial colonization. The new coating method utilizing LMW polymers opens a new avenue for the development of a novel class of thick, long-acting antibiofilm coatings.

Intramolecular Electrostatic Interactions Regulate Reactivity of Zwitterionic Functionalities in Amphiphilic Assemblies.

Consequences of intramolecular ionic interactions in determining the reactivity of functional groups are of interest because they provide insights into how nature deploys seemingly reactive functionalities to be rather ubiquitous. Of specific interest are the quaternary ammonium ions in lipids. In this work, we investigate the effect of intramolecular electrostatic interactions in zwitterionic functionalities by judiciously incorporating them as leaving groups at the α-position of an α,ß-unsaturated ester-based lipid headgroup. We find that electrostatic stabilization indeed plays a critical role in both the reaction kinetics with nucleophiles and the thermodynamics of lipid formation. We further leverage these findings to fabricate both triggerable assembly and disassembly of liposomal supramolecular assemblies in the presence of nucleophiles.

Bioengineered self-assembled nanofibrils for high-affinity SARS-CoV-2 capture and neutralization.

The recent coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spurred intense research efforts to develop new materials with antiviral activity. In this study, we genetically engineered amyloid-based nanofibrils for capturing and neutralizing SARS-CoV-2. Building upon the amyloid properties of a short Sup35 yeast prion sequence, we fused it to SARS-CoV-2 receptor-binding domain (RBD) capturing proteins, LCB1 and LCB3. By tuning the reaction conditions, we achieved the spontaneous self-assembly of the Sup35-LCB1 fusion protein into a highly homogeneous and well-dispersed amyloid-like fibrillar material. These nanofibrils exhibited high affinity for the SARS-CoV-2 RBD, effectively inhibiting its interaction with the angiotensin-converting enzyme 2 (ACE2) receptor, the primary entry point for the virus into host cells. We further demonstrate that this functional nanomaterial entraps and neutralizes SARS-CoV-2 virus-like particles (VLPs), with a potency comparable to that of therapeutic antibodies. As a proof of concept, we successfully fabricated patterned surfaces that selectively capture SARS-CoV-2 RBD protein on wet environments. Collectively, these findings suggest that these protein-only nanofibrils hold promise as disinfecting coatings endowed with selective SARS-CoV-2 neutralizing properties to combat viral spread or in the development of sensitive viral sampling and diagnostic tools.

Modulating ß-catenin homeostasis for cancer therapy.

ß-Catenin is a well-established driver of many cancers; however, there are challenges in developing agents targeting ß-catenin for clinical use. Recent progress has indicated that most of the pathological changes in ß-catenin may be commonly caused by loss of protein homeostasis. Modulation of ß-catenin homeostasis, especially by hyperactivation of ß-catenin, potentially leads to robust antitumor outcomes. Here, we comprehensively dissect the protein homeostasis of ß-catenin in terms of time, compartmentalization, supramolecular assemblies, and dynamics, with emphasis on changes in ß-catenin homeostasis upon oncogenic mutations. We propose that altered ß-catenin homeostasis could be deleterious for ß-catenin-dependent cancers and that modulation of ß-catenin homeostasis offers a novel avenue for targeting ß-catenin for cancer therapy.

Supramolecular Assembly Based on Calix(4)arene and Aggregation-Induced Emission Photosensitizer for Phototherapy of Drug-Resistant Bacteria and Skin Flap Transplantation.

Photodynamic therapy as a burgeoning and non-invasive theranostic technique has drawn great attention in the field of antibacterial treatment but often encounters undesired phototoxicity of photosensitizers during systemic circulation. Herein, a supramolecular substitution strategy is proposed for phototherapy of drug-resistant bacteria and skin flap repair by using macrocyclic p-sulfonatocalix(4)arene (SC4A) as a host, and two cationic aggregation-induced emission luminogens (AIEgens), namely TPE-QAS and TPE-2QAS, bearing quaternary ammonium group(s) as guests. Through host-guest assembly, the obtained complex exhibits obvious blue fluorescence in the solution due to the restriction of free motion of AIEgens and drastically inhibits efficient type I ROS generation. Then, upon the addition of another guest 4,4'-benzidine dihydrochloride, TPE-QAS can be competitively replaced from the cavity of SC4A to restore its pristine ROS efficiency and photoactivity in aqueous solution. The dissociative TPE-QAS shows a high bacterial binding ability with an efficient treatment for methicillin-resistant Staphylococcus aureus (MRSA) in dark and light irradiation. Meanwhile, it also exhibits an improved survival rate for MRSA-infected skin flap transplantation and largely accelerates the healing process. Thus, such cascaded host-guest assembly is an ideal platform for phototheranostics research.

Optimized Polymeric Membranes for Water Treatment: Fabrication, Morphology, and Performance.

Conventional polymers, endowed with specific functionalities, are extensively utilized for filtering and extracting a diverse set of chemicals, notably metals, from solutions. The main structure of a polymer is an integral part for designing an efficient separating system. However, its chemical functionality further contributes to the selectivity, fabrication process, and resulting product morphology. One example would be a membrane that can be employed to selectively remove a targeted metal ion or chemical from a solution, leaving behind the useful components of the solution. Such membranes or products are highly sought after for purifying polluted water contaminated with toxic and heavy metals. An efficient water-purifying membrane must fulfill several requirements, including a specific morphology attained by the material with a specific chemical functionality and facile fabrication for integration into a purifying module Therefore, the selection of an appropriate polymer and its functionalization become crucial and determining steps. This review highlights the attempts made in functionalizing various polymers (including natural ones) or copolymers with chemical groups decisive for membranes to act as water purifiers. Among these recently developed membrane systems, some of the materials incorporating other macromolecules, e.g., MOFs, COFs, and graphene, have displayed their competence for water treatment. Furthermore, it also summarizes the self-assembly and resulting morphology of the membrane materials as critical for driving the purification mechanism. This comprehensive overview aims to provide readers with a concise and conclusive understanding of these materials for water purification, as well as elucidating further perspectives and challenges.

Porous and Close Packed Supramolecular Assemblies from 2,4-Difluoronitrobenzene with Three Different Linkers and an n-Butylamine Cap.

A porous structure formed from sheets with cavities and two close packed structures were crystallised from building blocks prepared from 2,4-difluoronitrobenzene, a diamine linker and n-butylamine. The porous structure crystallised from a flexible building block prepared using 1,4-diaminobutane as linker. The close packed structures were prepared using either piperazine or 1,4-bis(aminomethyl)benzene as a linker and have less conformational freedom.

Weakly Self-Assembled [6]Helicenes: Circularly Polarized Light and Spin Filtering Properties.

Self-assembling features, chiroptical activity, and spin filtering properties are reported for 2,15- and 4,13-disubstituted [6]helicenes decorated in their periphery with 3,4,5-tris(dodecyloxy)-N-(4-ethynylphenyl)benzamide moieties. The weak non-covalent interaction between these units conditions the corresponding circularly polarized luminescence and spin polarization. The self-assembly is overall weak for these [6]helicene derivatives that, despite the formation of H-bonding interactions between the amide groups present in the peripheral moieties, shows very similar chiroptical properties both in the monomeric or aggregated states. This effect could be explained by considering the steric effect that these groups could generate in the growing of the corresponding aggregate formed. Importantly, the self-assembling features also condition chiral induced spin selectivity (CISS effect), with experimental spin polarization (SP) values found between 35-40 % for both systems, as measured by magnetic-conducting atomic force microscopy (AFM) technique.

Excitation-Dependent Fluorescence with Excitation-Selective Circularly Polarized Luminescence from Hierarchically Organized Atomic Nanoclusters.

Nanometer-scaled objects are known to have dimension-related properties, but sometimes the assembly of such objects can lead to the emergence of other properties. Here, we show the assembly of atomically precise gold nanoclusters into large fibrillar structures that are featuring excitation-dependent luminescence with an excitation-selective circularly polarized luminescence (CPL), even though all components are achiral. The origin of CPL in the assembly of atomic clusters has been attributed to the hierarchical organization of atomic clusters into fibrillar structures, mediated via a hydrogen bonding interaction with a surfactant. We follow the assembly process both experimentally and computationally showing the advance in the structural formation along with its chiroptical electronic properties, i.e., circular dichroism (CD) and CPL. Our study here can assist in the rational design of materials featuring chiroptical properties, thus leading to a controlled CPL activity.

Polyethylene glycol embedded reduced graphene oxide supramolecular assemblies for enhanced room-temperature gas sensors.

Herein, we present the gas-dependent electrical properties of a reduced graphene oxide nanocomposite. The reduced graphene oxide (rGO) was synthesized by reducing GO with sodium borohydride (NaBH4). As-synthesized rGO was dispersed in DI water containing 1, 2, 3, 4, and 5 wt% polyethylene glycol (PEG) to prepare PEG-rGO supramolecular assemblies. The successful preparation of supramolecular assemblies was verified by their characterization using XRD, FESEM, EDS, TEM, FTIR, and Raman spectroscopy. At room temperature, the gas-dependent electrical properties of these supramolecular assemblies were investigated. The results showed that sensors composed of PEG-rGO supramolecular assemblies performed better against benzene and methanol at 3% and 4% PEG, respectively. However, high selectivity and a wide range of activation energies (∼1.64-1.91 eV) were observed for H2 gas for 4% PEG-modified supramolecular assemblies. The PEG-rGO supramolecular assemblies may be an excellent candidate for constructing ultrahigh-performance gas sensors for a variety of applications due to their high sensitivity and selectivity.

Tunable Multicolor Lanthanide Supramolecular Assemblies with White Light Emission Confined by Cucurbituril[7].

Macrocyclic confinement-induced supramolecular luminescence materials have important application value in the fields of bio-sensing, cell imaging, and information anti-counterfeiting. Herein, a tunable multicolor lanthanide supramolecular assembly with white light emission is reported, which is constructed by co-assembly of cucurbit[7]uril (CB[7]) encapsulating naphthylimidazolium dicarboxylic acid (G1 )/Ln (Eu3+ /Tb3+ ) complex and carbon quantum dots (CD). Benefiting from the macrocyclic confinement effect of CB[7], the supramolecular assembly not only extends the fluorescence intensity of the lanthanide complex G1 /Tb3+ by 36 times, but also increases the quantum yield by 28 times and the fluorescence lifetime by 12 times. Furthermore, the CB[7]/G1 /Ln assembly can further co-assemble with CD and diarylethene derivatives (DAE) to realize the intelligently-regulated full-color spectrum including white light, which results from the competitive encapsulation of adamantylamine and CB[7], the change of pH, and photochromic DAE. The multi-level logic gate based on lanthanide supramolecular assembly is successfully applied in anti-counterfeiting system and information storage, providing an effective method for the research of new luminescent intelligent materials.

A Serum-Stable supramolecular drug carrier for chemotherapeutics fabricated by a Peptide-Photosensitizer conjugate.

Supramolecular assemblies fabricated by peptide-photosensitizer conjugates have attracted increasing attentions in recent years as drug carriers for chemotherapeutics (CTs). However, these assemblies have been known to suffer from disintegration by serum components leading to off-target drug release, and thereby impairing antitumor effects and causing systemic toxicities. To address this problem, this study reports a nano-architectural self-assembly peptide-photosensitizer carrier (NSPC) fabricated by conjugating a phthalocyanine derivative (MCPZnPc) and ε-poly-l-lysine (EPL). By engineering the core and peripheral interactions, MCPZnPC-EPL (M-E) NSPC firmly encapsulated multiple CTs, creating CT@M-E NSPCs that were highly stable against disintegration in serum. More importantly, CT@M-E NSPCs exhibited controlled release of CTs in tumor tissues. The antitumor effects of CTs were further promoted by the synergism with the reactivated photodynamic effect. Furthermore, M-E NSPC-encapsulation optimized CTs' biodistribution reducing adverse effects in vivo. This study provides a serum-stable supramolecular drug delivery system with photodynamic effect, which is applicable for a broad-range of CTs to promote antitumor effects and ameliorate adverse effects.

Interaction of Aggregated Cationic Porphyrins with Human Serum Albumin.

The interaction of an equilibrium mixture of monomeric and aggregated cationic trans-5,15-bis(N-methylpyridinium-4-yl)-10,15-bis-diphenylporphine (t-H2Pagg) chloride salt with human serum albumin (HSA) has been investigated through UV/Vis absorption, fluorescence emission, circular dichroism and resonant light scattering techniques. The spectroscopic evidence reveals that both the monomeric t-H2Pagg and its aggregates bind instantaneously to HSA, leading to the formation of a tight adduct in which the porphyrin is encapsulated within the protein scaffold (S430) and to clusters of aggregated porphyrins in electrostatic interaction with the charged biomolecules. These latter species eventually interconvert into the final S430 species following pseudo-first-order kinetics. Molecular docking simulations have been performed to get some insights into the nature of the final adduct. Analogously to hemin bound to HSA, the obtained model supports favorable interactions of the porphyrin in the same 1B subdomain of the protein. Hydrophobic and van der Waals energy terms are the main contributions to the calculated ΔGbind value of -117.24 kcal/mol.

Kinetic Investigations on the Chiral Induction by Amino Acids in Porphyrin J-Aggregates.

The self-assembling kinetics of the 5,10,15,20-tetrakis(4-sulfonato-phenyl)porphyrin (TPPS4) into nano-tubular J-aggregates under strong acidic condition and in the presence of amino acids as templating chiral reagents have been investigated through UV/Vis spectroscopy. The ability of the chiral species to transfer its chiral information to the final J-aggregate has been measured through circular dichroism (CD) spectroscopy and compared to the spontaneous symmetry breaking process usually observed in these nano-aggregates. Under the experimental conditions here selected, including mixing protocol, we have observed a large difference in the observed aggregation rates for the various amino acids, those with a positively charged side group being the most effective. On the contrary, these species are less efficient in transferring their chirality, exhibiting a quite low or modest enhancement in the observed dissymmetry g-factors. On the other side, hydrophobic and some hydrophilic amino acids are revealed to be very active in inducing chirality with a discrete increase of intensity of the detected CD bands with respect to the spontaneous symmetry breaking.

Construction of artificial light-harvesting systems based on a variety of polyelectrolyte materials and application in photocatalysis.

In the present work, we designed and synthesized a cationic cyano-substituted p-phenylenevinylene derivative (PPTA), which can form supramolecular assemblies through electrostatic interaction with a type of polyelectrolyte material anionic guar gum (GP5A). A polyelectrolyte-based artificial light-harvesting system (LHS) was constructed by selecting a fluorescent dye sulforhodamine 101 (SR101) that matched its energy level as an energy acceptor. The energy harvested by the acceptors was used in the aqueous phase cross dehydrogenation coupling (CDC) reaction with a yield of up to 87%. In addition, the general applicability of polyelectrolyte materials to build artificial LHS was demonstrated by three other polyelectrolyte materials sodium polyphenylene sulfonate (RSS), sodium carboxymethyl cellulose (CMC), and sodium polyacrylate (PAAS), in which the CDC reaction was also carried out by these three LHSs and obtained high yields. This work not only provides a new method to construct LHSs by using polyelectrolyte materials, but also provides a beneficial exploration for further applying the energy harvested in LHSs to the field of photocatalysis in an aqueous solution.

Assembly of Helical Nanostructures: Solvent-Induced Morphology Transition and Its Effect on Cell Adhesion.

Being able to precisely manipulate both the morphology and chiroptical signals of supramolecular assemblies will help to better understand the natural biological self-assembly mechanism. Two simple l/d-phenylalanine-based derivatives (L/DPFM) have been designed, and their solvent-dependent morphology evolutions are illustrated. It was found that, as the content of H2 O in aqueous ethanol solutions was increased, LPFM self-assembles first into right-handed nanofibers, then flat fibrous structures, and finally inversed left-handed nanofibers. Assemblies in ethanol and H2 O exhibit opposite conformations and circular dichroism (CD) signals even though they are constructed from the same molecules. Thus, the morphology-dependent cell adhesion and proliferation behaviors are further characterized. Left-handed nanofibers are found to be more favorable for cell adhesion than right-handed nanostructures. Quantitative AFM analysis showed that the L929 cell adhesion force on left-handed LPFM fibers is much higher than that on structures with inversed handedness. Moreover, the value of cell Young's modulus is lower for left-handed nanofibrous films, which indicates better flexibility. The difference in cell-substrate interactions might lead to different effects on cell behavior.

A comprehensive review on bio-mimicked multimolecular frameworks and supramolecules as scaffolds for enzyme immobilization.

Immobilization depicts a propitious route to optimize the catalytic performances, efficient recovery, minimizing autocatalysis, and also augment the stabilities of enzymes, particularly in unnatural environments. In this opinion, supramolecules and multimolecular frameworks have captivated immense attention to achieve profound controllable interactions between enzyme molecules and well-defined natural or synthetic architectures to yield protein bioconjugates with high accessibility for substrate binding and enhanced enantioselectivities. This scholastic review emphasizes the possibilities of associating multimolecular complexes with biological entities via several types of interactions, namely covalent interactions, host-guest complexation, π - π ${\rm{\pi }}-{\rm{\pi }}$ interactions, intra/inter hydrogen bondings, electrostatic interactions, and so forth offers remarkable applications for the modulations of enzymes. The potential synergies between artificial supramolecular structures and biological systems are the primary concern of this pedagogical review. The majority of the research primarily focused on the dynamic biomolecule-responsive supramolecular assemblages and multimolecular architectures as ideal platforms for the recognition and modulation of proteins and cells. Embracing sustainable green demeanors of enzyme immobilizations in a quest to reinforce site-selectivity, catalytic efficiency, and structural integrality of enzymes are the contemporary requirements of the biotechnological sectors that instigate the development of novel biocatalytic systems.

Agglomeration: when folded proteins clump together.

Protein self-association is a widespread phenomenon that results in the formation of multimeric protein structures with critical roles in cellular processes. Protein self-association can lead to finite protein complexes or open-ended, and potentially, infinite structures. This review explores the concept of protein agglomeration, a process that results from the infinite self-assembly of folded proteins. We highlight its differences from other better-described processes with similar macroscopic features, such as aggregation and liquid-liquid phase separation. We review the sequence, structural, and biophysical factors influencing protein agglomeration. Lastly, we briefly discuss the implications of agglomeration in evolution, disease, and aging. Overall, this review highlights the need to study protein agglomeration for a better understanding of cellular processes.

Proton Conducting Membranes with Molecular Self Assemblies and Ionic Channels for Efficient Proton Conduction.

Supramolecular assemblies are vital for biological systems. This phenomenon in artificial materials is directly related to their numerous properties and their performance. Here, a simple approach to supramolecular assemblies is employed to fabricate highly efficient proton conducting molecular wires for fuel cell applications. Small molecule-based molecular assembly leading to a discotic columnar architecture is achieved, simultaneously with proton conduction that can take place efficiently in the absence of water, which otherwise is very difficult to obtain in interconnected ionic channels. High boiling point proton facilitators are incorporated into these columns possessing central ionic channels, thereby increasing the conduction multifold. Larger and asymmetrical proton facilitators disintegrated the self-assembly, resulting in low proton conduction efficiency. The highest conductivity was found to be approaching 10-2 S/cm for the molecular wires in an anhydrous state, which is ascribed to the continuous network of hydrogen bonds in which protons can hop between with a lower energy barrier. The molecular wires with ionic channels presented here have potential as an alternative to proton conductors operating under anhydrous conditions at both low and high temperatures.

The First Noncovalent-Bonded Supramolecular Frameworks of (Benzylthio)Acetic Acid with Proline Compounds, Isonicotinamide and Tryptamine.

The co-crystallization of (benzylthio)acetic acid (HBTA) with L-proline (L-PRO), D-proline (D-PRO), DL-proline (DL-PRO), isonicotinamide (INA) and tryptamine (TPA) led to the formation of five novel crystalline compounds: L-PRO±·HBTA (1), D-PRO±·HBTA (2), DL-PRO±·HBTA (3), INA·HBTA (4) and TPA+·BTA- (5). The prepared supramolecular assemblies were characterized by single crystal X-ray diffraction, an elemental analysis, FT-IR spectroscopy and a thermal analysis based on thermogravimetry (TG) combined with differential scanning calorimetry (DSC). Additionally, their melting points through TG/DSC measurements were established. All fabricated adducts demonstrated the same stoichiometry, displayed as 1:1. The integration of HBTA with selected N-containing co-formers yielded different forms of multi-component crystalline phases: zwitterionic co-crystals (1-3), true co-crystal (4) or true salt (5). In the asymmetric units of 1-4, the acidic ingredient is protonated, whereas the corresponding N-containing entities take either the zwitterionic form (1-3) or remain in the original neutral figure (4). The molecular structure of complex 5 is occupied by the real ionic forms of both components, namely the (benzylthio)acetate anion (BTA-) and the tryptaminium cation (TPA+). In crystals 1-5, the respective molecular residues are permanently bound to each other via strong H-bonds provided by the following pairs of donor···acceptor: Ocarboxylic···Ocarboxylate and Npyrrolidinium···Ocarboxylate in 1-3, Ocarboxylic···Npyridine and Namine···Ocarboxylic in 4 as well as Nindole···Ocarboxylate and Naminium···Ocarboxylate in 5. The crystal structures of conglomerates 1-5 are also stabilized by numerous weaker intermolecular contacts, including C-H···O (1-3, 5), C-H···S (1, 2, 5), C-H···N (5), C-H···C (5), C-H···π (1-5) as well as π···π (4) interactions. The different courses of registered FT-IR spectral traces and thermal profiles for materials 1-5 in relation to their counterparts, gained for the pure molecular ingredients, also clearly confirm the formation of new crystalline phases.