Hydrophobic Alkyl Chains Research Articles

Effects of N-acylation on the immune adjuvanticity of analogs of the Quillaja saponins derivative GPI-0100

Modification of the 3-glucuronic acid (GlcA) residue from the Quillaja saponin (QS) adjuvants by N-acylation, yields derivatives with linear alkylamides that show structural and functional changes. Structural, since the relatively unreactive added hydrophobic alkyl chains may modify these glycosides’ conformation and micellar structure. Functional, because altering the availability of proposed pharmacophores, like fucose (Fucp) and aldehyde groups, to interact with their cellular receptors, may change these glycosides’ adjuvanticity. While deacylated QS (DS-QS) adjuvants bias the response toward a sole anti-inflammatory Th2 immunity against an antigen, their N-alkylated derivatives carrying octyl to dodecylamide residues, modify that response to a pro-inflammatory Th1 immunity. As shown by their IgG2a/IgG1 titer ratios, which are higher than those for Th2 immunity. A result of the fact that in mice, the IgG2a levels are dependent on the direct influence of secreted interferon-γ (IFN-γ), a crucial Th1 cytokine. But addition of the longer and more lipophilic tetradecylamide group, yields derivatives that like DS-QS induce Th2 immunity, as shown by their low IgG2a/IgG1 ratio. Results that imply that changes in these analogs’ conformation and micellar structure, would affect the immunomodulatory properties or adjuvanticity of N-acylated DS-QS. Physical changes that may alter the availability of groups like Fucp, to bind to its presumed dendritic cells’ lectin receptor DC-SIGN; an essential step in the stimulation of Th2 immunity. Structural properties that in an aqueous environment, would depend on these glycosides’ balance of their hydrophilic and lipophilic moieties (HLB), and the interactions of the newly introduced alkyl chain with the native QS’ lipophilic triterpene aglycone and hydrophilic oligosaccharide chains. A situation that would explain these new derivatives’ qualitative and quantitative changes in adjuvanticity.

Cationic surfactant-assisted delamination of disorderly layered clinoptilolites for selective adsorption of CO2 and CH4

With the assistance of cetyltrimethyl ammonium bromide (CTAB), the delamination of disorderly layered clinoptilolite (CP) was performed. The introduction of CTAB in hydrothermal system was beneficial to stratification of CP lamellas by enlarging interlayer spacing, and thus accelerating the formation of disordered CP nanosheets. The hydrophobic alkyl chain restricts the crystal growth along a-axis and the few-layer CP lamellas with integrally preserved heulandite structures were obtained by ultrasonic treatment and HNO3 modification at room temperature. Meanwhile, the CTAB-assisted crystallization mechanism was further elucidated, in which, the amorphous spherical nanoparticles were firstly generated and then transformed into the fibrous and lamellar species. Finally, the flower-like CP morphologies with the aggregated nanosheets appeared. Meanwhile, the selective adsorptions and separations of CO2 and CH4 using these delaminated CPs as the absorbents were preliminarily explored, showing a strong potential in the mixed gases separation applications. This approach is a promising strategy for constructing delaminated zeolites with low n(SiO2/Al2O3), which may open a new avenue for the delaminated CP nanosheet applications in gas adsorption and separation fields.

3D Printable Composite Polymer Electrolytes: Influence of SiO2 Nanoparticles on 3D-Printability.

We here demonstrate the preparation of composite polymer electrolytes (CPEs) for Li-ion batteries, applicable for 3D printing process via fused deposition modeling. The prepared composites consist of modified poly(ethylene glycol) (PEG), lithium bis(trifluoromethylsulfonyl)imide (LiTFSI) and SiO2-based nanofillers. PEG was successfully end group modified yielding telechelic PEG containing either ureidopyrimidone (UPy) or barbiturate moieties, capable to form supramolecular networks via hydrogen bonds, thus introducing self-healing to the electrolyte system. Silica nanoparticles (NPs) were used as a filler for further adjustment of mechanical properties of the electrolyte to enable 3D-printability. The surface functionalization of the NPs with either ionic liquid (IL) or hydrophobic alkyl chains is expected to lead to an improved dispersion of the NPs within the polymer matrix. Composites with different content of NPs (5%, 10%, 15%) and LiTFSI salt (EO/Li+ = 5, 10, 20) were analyzed via rheology for a better understanding of 3D printability, and via Broadband Dielectric Spectroscopy (BDS) for checking their ionic conductivity. The composite electrolyte PEG 1500 UPy2/LiTFSI (EO:Li 5:1) mixed with 15% NP-IL was successfully 3D printed, revealing its suitability for application as printable composite electrolytes.

Synthesis of cationic waterborne polyurethane via thiol-ene click reaction and catechol chemistry to improve the performance of soybean meal adhesives

The development of bio-based adhesives comprised of low-cost, renewable, and accessible biomass resources with high adhesion and toughness is needed in wood-based panel industry. Herein, a novel cationic waterborne polyurethane (CWPU) emulsion was prepared with a hydrophobic long alkyl chain and catechol structure via thiol-ene click reaction and direct emulsification. Then, the obtained emulsions were applied as efficient crosslinkers to enhance the bonding performance of soybean meal (SM) adhesives. The catechol group on polyurethane acted as a secondary reaction platform that formed multiple hydrogen bonds with protein molecules to optimize the mechanical strength and adhesion toughness of the SM resins. In addition, the hydrophobic alkyl chains grafted intertwine and served as a “water-proofer” that hindered the intrusion of water molecules. Consequently, the modified SM/HD@CCWPU resin presented an impressive improvement in its wet bonding strength and toughness to 165.9% and 378.1%, respectively, compared with the pure SM resin. This efficient, ecofriendly, and low-cost design enables the utilization of agricultural byproducts instead of traditional formaldehyde-based products to prepare high-performance adhesives.

Perovskite films passivated by a dendrimer toward high efficiency and high stability devices

Passivation engineering has become one of the most effective and convenient strategies to enhance the performance and the stability of perovskite solar cells (PSCs). We design a new material, fatty acid-polyamidoamine-COOH (FPC), with sixteen long alkyl chains and eight carboxylic acid functional groups. The carboxylic acid can passivate the Pb defects at the surface and grain boundaries (GBs). Self-arrangement of the FPC molecules on the surface results in improved surface potential. FPC passivation leads to suppressed charge recombination, enhanced charge carrier transport, and increased light-harvesting. The transient absorption measurements confirm the key role of FPC passivation on the recombination at the interface between perovskite and PC61BM layer in PSCs. The power conversion efficiency (PCE) of PSCs modified by FPC increases to 21.01% with Jsc 23.74 mA/cm2, Voc 1.09 V, and FF 81.16%. Furthermore, the hydrophobic long alkyl chains improve the device stability. Under 60 ± 5% relative humidity (RH), the PSCs with FPC passivation maintain ∼90% of the initial PCE for 3500 min, but the control PSCs only keep ∼50% of the origin PCE. In addition, the devices modified by FPC could maintain ∼82% of the initial PCE value under 25 ± 5% (RH) and 30 ± 5 °C ambient environment for 30 days. This work provides a guideline for designing passivants to improve the efficiency and stability of devices.

Hydrophobicity regulates self-assembly behavior of binding-induced fibrillogenesis peptides

Binding-induced fibrillogenesis (BIF) peptides have a promising future in biomedicine due to the processiblity in situ in vivo, which bind to a specific trigger and in situ self-assemble into nanofibrous structures (BIF process) with excellent physical/biological functions. Alkyl chains in BIF peptides as hydrophobic tails have an important effect on self-assembly behaviors of BIF peptides. Herein, BIF peptides (trigger: Ca2+ or integrin) with different hydrophobic alkyl chains are designed to explore the influence of hydrophobicity on self-assembly behaviors of BIF peptides (Abbreviation as BIF4, BIF8, and BIF16 for 4, 8, 16 carbons of alkyl chains). It is found that BIF peptides with weak hydrophobicity (BIF4) do not form fibrous structure upon binding to Ca2+, but in nanoparticle formulation. While with strong hydrophobicity, BIF16 initially self-assemble into nanoparticles, which further bind to Ca2+ and self-assemble into nanofibers with a β-sheet conformation. As a result, when incubated with HUVECs overexpressing integrins on surfaces, BIF4 were internalized as nanoparticles without BIF process, but BIF16 performed BIF process and attached on cell surfaces. This study provides experimental evidences of the hydrophobicity effect on self-assembly behavior of BIF peptides and directs applications of BIF peptides with controllable self-assembly

Cationic Amphiphilic Dendrons with Anticancer Activity.

Cancer has become the leading cause of human death worldwide, and there is an urgent need to design and develop new oncology drugs. In this study, we report series of cationic amphiphilic dendrons with different hydrophobic alkyl chains (Cn) and different generations (Gx) and demonstrate their use for anticancer applications. The results revealed that lower-generation dendrons (G1) with a longer hydrophobic alkyl chain (C12 and C18) have stronger antitumor activity. Among these dendrons, a lead candidate C12-G1 was identified that demonstrated excellent broad-spectrum antitumor activity in 7 cancer cell lines including highly metastatic tumor cells, while simultaneously, hemolysis was negligible. Mechanistic studies showed that C12-G1 could lead to cytoplasmic leakage and induce cancer cell necrosis through membrane disruption. In addition, C12-G1 showed potent inhibition of tumor growth in a B16-F10 melanoma model. In conclusion, these findings demonstrate that the cationic amphiphilic dendron might be a promising agent for anticancer application.

Small Molecules Modulate Liquid-to-Solid Transitions in Phase-Separated Tau Condensates.

In Tau protein condensates formed by the Liquid-Liquid Phase Separation (LLPS) process, liquid-to-solid transitions lead to the formation of fibrils implicated in Alzheimer's disease. Here, by tracking two contacting Tau-rich droplets using a simple and nonintrusive video microscopy, we found that the halftime of the liquid-to-solid transition in the Tau condensate is affected by the Hofmeister series according to the solvation energy of anions. After dissecting functional groups of physiologically relevant small molecules using a multivariate approach, we found that charged groups facilitate the liquid-to-solid transition in a manner similar to the Hofmeister effect, whereas hydrophobic alkyl chains and aromatic rings inhibit the transition. Our results not only elucidate the driving force of the liquid-to-solid transition in Tau condensates, but also provide guidelines to design small molecules to modulate this important transition for many biological functions for the first time.

Small Molecules Modulate Liquid‐to‐Solid Transitions in Phase‐Separated Tau Condensates

AbstractIn Tau protein condensates formed by the Liquid–Liquid Phase Separation (LLPS) process, liquid‐to‐solid transitions lead to the formation of fibrils implicated in Alzheimer's disease. Here, by tracking two contacting Tau‐rich droplets using a simple and nonintrusive video microscopy, we found that the halftime of the liquid‐to‐solid transition in the Tau condensate is affected by the Hofmeister series according to the solvation energy of anions. After dissecting functional groups of physiologically relevant small molecules using a multivariate approach, we found that charged groups facilitate the liquid‐to‐solid transition in a manner similar to the Hofmeister effect, whereas hydrophobic alkyl chains and aromatic rings inhibit the transition. Our results not only elucidate the driving force of the liquid‐to‐solid transition in Tau condensates, but also provide guidelines to design small molecules to modulate this important transition for many biological functions for the first time.

Interaction of bisdemethoxycurcumin with sodium dodecyl sarcosine + Tween 20/Tween 60 mixed surfactants: Insights from multispectral analysis and solubilization effect

The low aqueous solubility of curcuminoids, including bisdemethoxycurcumin (BDMC), severely limits their applications in the food and pharmaceutical industries. This improvement is expected to be achieved by encapsulating them with mixed surfactant micellar systems. In this study, the interaction of BDMC with sodium dodecyl sarcosine (SDDS) + Tween 20/Tween 60 mixed micelles was studied at the molecular level. The molar ratio of Tween 20/Tween 60 to SDDS in the mixed micelles was optimized using response surface methodology. The binding parameters of BDMC to the mixed micelles were determined by fluorescence and UV–vis absorption spectroscopy. Thermodynamic analysis showed that the hydrophobic interaction was dominant in the binding process. The longer hydrophobic chain of Tween 60 was responsible for the stronger interaction of BDMC with SDDS + Tween 60. The binding site of BDMC in the hydrophobic alkyl chains of the mixed micelles was analyzed by copper ion fluorescence quenching analysis, fluorescence polarization analysis, 1H nuclear magnetic resonance spectroscopy, and time-resolved fluorescence spectroscopy. The solubility of BDMC in the mixed micelles was enhanced and SDDS + Tween 60 had more significant solubilization capacity. Therefore, the mixed micellar systems may provide a feasible solution for the application of BDMC in functional food and medicine fields.

Coordination‐Driven Terpyridine‐Based Twisted Prisms with Tunable Emissions and Hierarchical Self‐Assembly Properties

AbstractTunable fluorescence emission materials play a critical role in many fields such as biology and chemistry. With respect to metallo‐supramolecular assemblies, the construction of 3D tunable‐fluorescent supramolecular assemblies with 2,2′:6′,2″‐terpyridine (tpy) is still in its infancy. In this study, two luminous 3D supramolecular prisms self‐assembled with two terpyridine‐based tetraphenylethylene (TPE) ligands and metal Zn(II) are prepared, and the influence of hydrophobic alkyl chains on tunable fluorescence is further explored. By exploiting hydrophobic properties, the prism SA exhibits tunable visible‐light emission in the molecular‐aggregated state. Moreover, SA forms left‐hand and right‐hand helical nanofibers by hierarchical self‐assembly. However, the prism SB without hydrophobic chains does not exhibit tunable fluorescence emission, and only random spherical aggregates after hierarchical self‐assembly are formed. This study can aid to further strengthen the understanding about the effect of hydrophobic segments on photophysical properties and hierarchical self‐assembly of discrete supramolecular architectures.

Catechol modification of non-woven chitosan gauze for enhanced hemostatic efficacy

Development of efficient hemostatic gauze is critical to increasing survival rate by quick bleeding control of life-threatening hemorrhage. Herein, a novel chitosan non-woven hemostatic gauze is made by slightly surface modification with a special catechol compound, i.e. 3-(9,11,13-pentadecatrienyl)-1,2-benzenediol with a long side hydrophobic alkyl chain. Its wettability, interaction with red blood cell and platelet, and hemostatic efficacy on rat injuries are evaluated. This chitosan-catechol gauze demonstrates impressive hemostatic performances on rat femoral artery and liver laceration injury models (blood loss of this modified chitosan gauze is less than 17% of that of pristine chitosan gauze). Additionally, it is biodegradable, and maintains non-cytotoxicity. It integrates three structure and function effects together, i.e., anchoring effect between catechol and tissue, blood repelling effect from hydrophobic alkyl chain, and blood wicking effect from hydrophilic chitosan. Therefore, a new hemostatic mechanism is proposed for the excellent hemostatic potentials of this chitosan gauze.

Role of Ionic Strength in the Formation of Stable Supramolecular Nanoparticle-Protein Conjugates for Biosensing.

Monolayer-protected gold nanoparticles (AuNPs) exhibit distinct physical and chemical properties depending on the nature of the ligand chemistry. A commonly employed NP monolayer comprises hydrophobic molecules linked to a shell of PEG and terminated with functional end group, which can be charged or neutral. Different layers of the ligand shell can also interact in different manners with proteins, expanding the range of possible applications of these inorganic nanoparticles. AuNP-fluorescent Green Fluorescent Protein (GFP) conjugates are gaining increasing attention in sensing applications. Experimentally, their stability is observed to be maintained at low ionic strength conditions, but not at physiologically relevant conditions of higher ionic strength, limiting their applications in the field of biosensors. While a significant amount of fundamental work has been done to quantify electrostatic interactions of colloidal nanoparticle at the nanoscale, a theoretical description of the ion distribution around AuNPs still remains relatively unexplored. We perform extensive atomistic simulations of two oppositely charged monolayer-protected AuNPs interacting with fluorescent supercharged GFPs co-engineered to have complementary charges. These simulations were run at different ionic strengths to disclose the role of the ionic environment on AuNP–GFP binding. The results highlight the capability of both AuNPs to intercalate ions and water molecules within the gold–sulfur inner shell and the different tendency of ligands to bend inward allowing the protein to bind not only with the terminal ligands but also the hydrophobic alkyl chains. Different binding stability is observed in the two investigated cases as a function of the ligand chemistry.

Carbohydrate-substituted N-heterocyclic carbenes Palladium complexes: High efficiency catalysts for aqueous Suzuki–Miyaura reaction

Metal complexes that contain carbohydrate-substituent (Carb-) N-heterocyclic carbenes (NHCs) ligand have demonstrated great success as catalysts for organic synthesis reactions. In this study, four new Carb-NHC-Pd complexes 2a-d were prepared and their catalytic activities for Suzuki–Miyaura reaction were evaluated. The Carb-NHC-Pd complex behaved as a general surfactant which leads to the formation of a temporary oil-in-water contact interface, thereby promoting the Suzuki–Miyaura reaction. A long hydrophobic alkyl chain (–nC16H33) was remotely linked to complex 2d, in which Carb-NHCs showed high electron-donating properties, and steric bulk with 1JCH constant of 1H NMR. Complex 2d exhibited a higher catalytic activity as compared with 2a (–nC2H5), 2b (–nC4H9), and 2c (–nC8H17). A series of fluorene-cored materials with different aryl groups were synthesized with high yields (34 examples, 91–99%) under the optimized reaction conditions.

Enhanced catalytic performance of palladium nanoparticles in MOFs by channel engineering

The embedding of metal nanoparticles in MOFs is highly relevant in catalysis research. The MOF matrix prevents the NMP agglomeration. Furthermore, the MOF can easily be functionalized to design an optimal chemical environment for the benefit of a catalytic reaction. We report on a series of [email protected] materials, namely [email protected] and [email protected]nip, consisting of the structural prototype CuBTC (= [Cu3BTC2]; BTC = benzene-1,3,5-tricarboxylate). Pd NPs were incorporated by rapid “bottle-around-the-ship” encapsulation. Regulation of the microenvironment around the Pd NPs by using alkoxy-functionalized fragmented linkers H2Cnip (n = 3, 6, 10) allows to adjust the hydrophobicity. These modifications significantly improve the catalytic activity for alkene hydrogenation compared with [email protected] Our work suggests that the “channel engineering,” i.e., the introduction of hydrophobic alkyl chains to the MOF linkers, increases the interactions with non-polar substrates, leading to a facilitated substrate diffusion in the host, which is an efficient way to optimize the [email protected] catalysts.

Efficient, biosafe and tissue adhesive hemostatic cotton gauze with controlled balance of hydrophilicity and hydrophobicity

Cotton gauze is a widely used topical hemostatic material for bleeding control, but its high blood absorption capacity tends to cause extra blood loss. Therefore, development of rapid hemostatic cotton gauze with less blood loss is of great significance. Here, we develop an efficient hemostatic cotton gauze whose surface is slightly modified with a catechol compound which features a flexible long hydrophobic alkyl chain terminated with a catechol group. Its hemostatic performance in animal injuries is superior to standard cotton gauze and Combat GauzeTM. Its biosafety is similar to cotton gauze and rebleeding hardly occurs when the gauze is removed. Here, we show its hemostatic capability is attributable to the rapid formation of big and thick primary erythrocyte clots, due to its effective controlling of blood movement through blocking effect from tissue adhesion by catechol, blood wicking in cotton, and the hydrophobic effect from long alkyl chains.

Highly Efficient Electrogenerated Chemiluminescence Quenching on Lipid-Coated Multifunctional Magnetic Nanoparticles for the Determination of Proteases.

This work reports a highly efficient electrogenerated chemiluminescence (ECL) quenching on lipid-coated multifunctional magnetic nanoparticles (MMNP) for the determination of proteases incorporating membrane-confined quenching with a specific cleavage reaction for the first time. A new ruthenium complex [Ru(bpy)2(ddcbpy)](PF6)2 (bpy = 2,2'-bipyridine, ddcbpy = 4,4'-didodecyl-carbonyl-2,2'-bipyridine with two hydrophobic long alkyl chains) was synthesized as a signal probe, while [cholesterol-(CH2)6-HSSKLQK(peptide)-ferrocene (quencher)] was designed as a specific peptide-quencher probe. The MMNP were prepared by inserting both the signal probe and the peptide-quencher probe into the cholesterol-phospholipid-coated Fe3O4 magnetic nanoparticles (Fe3O4 NP, ∼200 nm). When prostate specific antigen (PSA) taken as a model analyte was introduced into the suspension of MMNP, PSA cleaved the amide bond of SK in cholesterol-(CH2)6-HSSKLQK-Fc, and then the cleaved peptide-motif-Fc-quencher was deviated from the MMNP, resulting in the increase in the ECL intensity. It was found that the ECL quenching constant of [Ru(bpy)2(ddcbpy)]2+ on MMNP (KSV,NP/lipECL =2.68 × 107 M-1) is 137-folds higher than that on the lipid-coated electrode (KSV,lipECL=1.95 × 105 M-1) and 391-folds higher than that in the solution (KSV,aqECL =6.86 × 104 M-1). The ECL emission of Ru(bpy)32+ derivative-attached Fe3O4 NP was observed at ∼1.2 V, involving the tunnel-electron transfer pathway (TPA• + Ru(bpy)33+ = Ru(bpy)32+*). Based on the highly efficient ECL quenching of the ruthenium complex by ferrocene on the MMNP, a new ECL method was developed for PSA with a linear range from 0.01 to 1.0 ng/mL and a limit of detection of 3.0 pg/mL. This work demonstrates that the approach of ECL quenching by ferrocene on lipid-coated Fe3O4 NP is promising and could be easily extended to determine other proteases.

Nanostructuring the Interior of Stimuli-Responsive Microgels by N-Vinylimidazoles Quaternized with Hydrophobic Alkyl Chains

The functionality of stimuli-responsive microgels can be tailor-made by manipulating their internal nanostructure induced by the chemical composition and morphology of the polymer network. Microgels with phase-separated domains on a nanoscopic length scale were synthesized by copolymerization of N-vinylcaprolactam (VCL) and amphiphilic-to-hydrophobic 1-vinyl-3-alkylimidazolium (VIM+CnH2n+1) bromides (Br–) of different alkyl chain lengths (n = 12, 14, 16) as comonomers. These quaternized imidazoles provide dual functionality for immobilization of payload by electrostatic and hydrophobic interactions. The morphologies and properties of synthesized poly(VCL-co-VIM+CnH2n+1Br–) microgels with 10 mol % comonomer were investigated systematically by 1H and 13C high-resolution NMR spectroscopy and relaxometry. Chemical side-selective information about the monomers’ volume-phase transition temperatures, width of transition, and change in transition entropy was reported and correlated to the alkyl chain length of the VIM+CnH2n+1Br– comonomer. 13C NMR spectroscopy reveals the existence of trans and gauche conformers of alkyl chains, which depends on the alkyl chain length and temperature. Morphologies and dynamic contrasts of alkyl chain domains and VCL moieties of poly(VCL-co-VIM+CnH2n+1Br–) microgels were investigated by 1H transverse magnetization relaxation (T2-relaxation). Finally, the microgels were successfully applied in the uptake of the hydrophobic dye Nile red, proving their ability to solubilize hydrophobic substances. In addition, the poly(VCL-co-VIM+CnH2n+1Br–) microgels were utilized in electrostatic interactions, as well as simultaneous addition of hydrophobic and negatively charged payload as a proof of concept for dual functionality. This investigation will allow for a better understanding of the internal nanophase structure of complex poly(N-vinylcaprolactam) (PVCL)-based microgels comprising pH-independent positive charges, as well as hydrophobic compartments, which have potential application as dual-functional delivery systems.

Cationic amphiphilic dendrons with effective antibacterial performance.

Bacterial infections and antibiotic resistance have become a global healthcare crisis. Herein, we designed and synthesized a series of cationic amphiphilic dendrons with cationic dendrons and hydrophobic alkyl chains for potential antibacterial applications. Our results showed that the antimicrobial activities of the cationic amphiphilic dendrons were highly dependent upon the length of the hydrophobic alkyl chain, whereas the number of cationic charges was less important. Among these cationic amphiphilic dendrons, a prime candidate was identified, which possessed excellent antimicrobial activity against various pathogens (minimum inhibitory concentrations of 9, 3, and 3 μg mL-1 for Escherichia coli, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus, respectively). Scanning electron microscopy and fluorescence microscopy analyses showed that it could disrupt the integrity of a pathogen's membrane, leading to cell lysis and death. In addition, in vitro bacteria-killing kinetics showed that it had rapid bactericidal efficiency. It also had excellent antimicrobial activities against MRSA in vivo and promoted wound healing. In general, the synthesized cationic amphiphilic dendrons, which exhibited rapid and broad-spectrum bactericidal activity, may have great potential in antimicrobial applications.

Dynamic self-assembling supramolecular dendrimer nanosystems as potent antibacterial candidates against drug-resistant bacteria and biofilms.

The alarming and prevailing antibiotic resistance crisis urgently calls for innovative "outside of the box" antibacterial agents, which can differ substantially from conventional antibiotics. In this context, we have established antibacterial candidates based on dynamic supramolecular dendrimer nanosystems self-assembled with amphiphilic dendrimers composed of a long hydrophobic alkyl chain and a small hydrophilic poly(amidoamine) dendron bearing distinct terminal functionalities. Remarkably, the amphiphilic dendrimer with amine terminals exhibited strong antibacterial activity against both Gram-positive and Gram-negative as well as drug-resistant bacteria, and prevented biofilm formation. Multidisciplinary studies combining experimental approaches and computer modelling together demonstrate that the dendrimer interacts and binds via electrostatic interactions with the bacterial membrane, where it becomes enriched and then dynamically self-assembles into supramolecular nanoassemblies for stronger and multivalent interactions. These, in turn, rapidly promote the insertion of the hydrophobic dendrimer tail into the bacterial membrane thereby inducing bacterial cell lysis and constituting powerful antibacterial activity. Our study presents a novel concept for creating nanotechnology-based antibacterial candidates via dynamic self-assembly and offers a new perspective for combatting recalcitrant bacterial infection.