Critical Aggregation Concentration Values Research Articles

Synthesis and self-assembly behaviors of α-galactosyl ceramide (1,2)-polysaccharide analogue

α-Galactosyl ceramide (GalCer) as a glycolipid has been long used as a standard reference for positive control in natural killer T cell studies. The (1,2)-disaccharide analogue of GalCer attracts a special attention in the study of lysosomal glycolipid processing. This paper describes the synthesis and self-assembly behaviors of GalCer 1,2-polysaccharide analogue (PolyGalCer), having considered the 1,2-disaccharide analogue as a structural motif. The synthesis of PolyGalCer is performed via one-pot glycosidation technique of 1,2-linked oligogalactan exploiting chain polymerization of galactose-based cyclic sulfite as a monomer initiated with ceramide-based alcoholic aglycon. Through the concentration dependence of PolyGalCer solutions in water or in MeOH on the turbidity, it is found that PolyGalCer forms associates in both media. From the intersection points, the critical aggregation concentration (CAC) values of PolyGalCer in water and MeOH were estimated. To know the self-assembly and the thermal transition behaviors, we performed dynamic light scattering (DLS) analysis of the associates comprising PolyGalCer in water. The transmission electron microscopy observations of the aqueous sample solution indicate that the solution of PolyGalCer includes large spherical associates. The results clarify that the 1,2-galactan moiety of PolyGalCer skeleton contributes on the kinetic inhibition of large associate formation and the metamorphosis of associates.

Critical Aggregation Concentration Can be a Predictor of Doxorubicin Delivery Performance of Self-Assembling Amphiphilic Peptides with Different Hydrophobic Tails

Amphiphilic peptides hold great potential as drug delivery systems. A popular peptide design approach has been to place amino acids in the peptide sequence based on their known properties. On the other hand, the directed discovery approach aims to screen a sequence space for a desired property. However, screening amphiphilic peptides for desirable drug delivery properties is not possible without a quantity that is predictive of these properties. We studied the predictive power of critical aggregation concentration (CAC) values on the drug delivery performance of a series of amphiphilic peptides with different hydrophobic tails and close CAC values. The CAC values were predicted by our previously developed model and doxorubicin was used as a model hydrophobic drug. All peptides showed close drug loading, entrapment efficiency, and release profile. They also formed similar spherical particles by assembling in reverse β-sheet arrangements regardless of drug presence. Moreover, the assembled particles were able to accumulate doxorubicin inside ordinary as well as drug-resistant breast cancer cells and enhance its toxicity up to 39 and 17 folds, respectively. It can be concluded that similar drug delivery properties displayed by the peptides can be attributed to their similar hydrophilic-lipophilic balance as reflected in their close CAC values.

Mixed Aggregates of Surface-Active Ionic Liquids and 14-2-14 Gemini Surfactants in an Aqueous Medium as Fluid Scaffolds for Enzymology of Cytochrome-c.

The aggregation behavior of the surface-active ionic liquid (SAIL), 3-(2-(hexadecyloxy)-2-oxoethyl)-1-methyl-1H-imidazol-3-ium chloride, [C16Emim][Cl], and a gemini surfactant (GS) (14-2-14) in the whole mole fraction range has been investigated in an aqueous medium employing various techniques. Experimentally obtained values of critical aggregation concentration (cac) are in good agreement with the theoretical cac values obtained using Clint's equation. Rubingh's model has been employed to evaluate the extent of synergistic interactions between two components, which has been found to be dependent upon the composition of a mixture of surfactants. The polarity index, hydrodynamic diameter (Dh), zeta potential (ζ-Pot.), and morphology of the aggregates have been found to be dependent upon the extent of hydrophobic as well as dipolar interactions and the degree of counterion binding governed by the content of the GS in mixed aggregates. Thermodynamic parameters evaluated employing isothermal titration calorimetry have revealed the aggregation as an entropy-driven process. Density functional theory calculations provide a detailed account of the SAIL-GS interactions at the molecular level. The reduced density gradient (RDG) along with the calculated isosurfaces asserts that the dominant interactions are noncovalent interactions. Furthermore, the enzymology of cytochrome-c in the aqueous SAIL-GS aggregated systems has been investigated and a two-fold increase in the enzyme activity has been observed in the aggregates formed by the GS as compared to that in buffer.

De novo designed self-assembling helicomimetic lipooligoureas with antibacterial activity

The overuse of antibiotics has led to a rise in infections caused by multidrug-resistant bacteria, resulting in a need for new antibacterial compounds with different modes of action. In this paper, we describe a new class of compounds called lipooligoureas, which are foldamer-based mimetics of antimicrobial lipopeptides. The lipooligoureas consist of an acyl chain connected to the N-terminus of an oligourea head group that exhibits a well-defined 2.5-helix secondary structure, which is further stabilized by the attachment of the lipophilic chain to the oligourea moiety. These compounds meet the established criteria for membranolytic compounds by possessing an amphiphilic structure that promotes the internalization and partitioning of the molecules into the lipid membrane. The presence of positively charged urea residues promotes electrostatic interactions with the negatively charged bacterial membrane. The subtle structural differences in oligourea head group influence the compounds' aggregation behavior, with the number and position of positively charged urea residues correlating with their aggregation ability. The biological activity of these compounds in inhibiting bacterial growth is correlated with their ability to aggregate, with stronger antibacterial properties exhibited by those that aggregate more easily. However, the concentration inhibiting bacterial growth is significantly lower than the critical aggregation concentration values, suggesting that the mechanism of action involves the monomeric forms of lipooligoureas. Nonetheless, a mechanism based on membrane-induced aggregation cannot be ruled out. The lipooligoureas exhibit higher activity towards Gram-positive bacteria than against Gram-negative bacteria, which is indicative of certain selectivity of these compounds. It is also demonstrated that lipooligoureas exhibit increased stability against proteolytic degradation in human blood serum.

Aggregation of ionic liquids with organic anions, driven by cation–anion interaction strength

The properties of ionic liquids (ILs) are related to the structure of their ions, which determines the nature of the cation–anion interaction. However, the direct effect that the structure has on properties such as aggregation and surface activity is not precise, especially when involving dicationic ILs with organic anions. In this study, the aggregation behaviour of imidazolium-based dicationic (1,8-bis(3-methylimidazolium-1-yl)octane - [C8(MIM)2]) ILs containing ibuprofenate [Ibu] and ascorbate [Asc] were evaluated (using conductivity and surface tension) and this was related to the cation–anion interaction strength determined using hydrogen nuclear magnetic resonance and surface plasmon resonance. The results showed that both ILs had a critical aggregation concentration value that was quite low compared to the analogue with a bromide anion. The [C8(MIM)2][2Asc] IL, which has the less hydrophobic anion and has more polar sites, had a greater cation–anion interaction strength and a lower critical aggregation concentration than the [C8(MIM)2][2Ibu] analogue. The cation–anion strength reflected the aggregation properties; for example, [C8(MIM)2][2Asc] had thermodynamically favoured aggregation and better packing of IL monomers at the air–water interface. These results are considered to be relevant for future studies related to the transport and drug loading associated with the use of these ILs.

Self-Assembly, In Vitro Gene Transfection, and Antimicrobial Activity of Biodegradable Cationic Bolaamphiphiles.

Bolaamphiphiles or bolaforms have drawn particular interest in drug and gene delivery, and studies of bolaforms have been growing continuously. Bolaforms, due to their unique structure, exhibit specific self-assembly behavior in water. The present work aims to develop biodegradable cationic bolaforms with a better gene transfection ability. In this work, a novel cationic bolaform (Bola-1) with head groups bearing hydroxyl (OH) functionality was designed and synthesized to investigate self-assembly and gene transfection efficiency. The self-assembly behavior of Bola-1 in water was compared with that of the hydrochloride salt (Bola-2) of its precursor molecule to investigate the effect of the -OH functionality on their solution properties. Several techniques, including surface tension, electrical conductivity, fluorescence probe, calorimetry, dynamic light scattering, and atomic force microscopy, were employed for the physicochemical characterization of Bola-1 and Bola-2. Despite the presence of polar urea groups in the spacer chain, both bolaforms were found to form spherical or elongated micelles above a relatively low critical aggregation concentration (CAC). The presence of the OH group was found to significantly affect the CAC value. The results of calorimetric measurements suggested a thermodynamically favorable aggregate formation in salt-free water. Despite stronger binding efficiency with calf thymus DNA, in vitro gene transfection studies performed using adherent cell Hek 293 suggested that both Bola-1 and Bola-2 have gene transfection efficiency comparable to that of turbofectamine standard. Both bolaforms were found to exhibit significant in vitro cytotoxicity at higher concentrations. Also, the bolaforms showed beneficial antibacterial activity at higher concentrations.

Development of New Alkylated Carrageenan Derivatives: Physicochemical, Rheological, and Emulsification Properties Assessment

In this research, amphiphilic derivatives of kappa carrageenan (KC) were synthesized by hydrophobic modification with an alkyl halide (1-Octyl chloride). Three hydrophobic polymers with different degrees of substitution (DS) were obtained by the Williamson etherification reaction in an alkaline medium. The effect of the molar ratio (R = reagent/polymer) on the DS was investigated at different ratios (1, 2, and 3). The KC derivatives (KCRs) were characterized by different techniques such as FT-IR, 1H-NMR, X-ray Diffraction, Scanning electron microscopy, and a rheological assessment. The FT-IR and 1HNMR analyses confirmed the binding of the hydrophobic groups onto the KC molecule. The degrees of substitution calculated by 1H-NMR demonstrated that the derivative KCR3 (0.68) presented a higher degree of substitution compared to KCR1(0.45) and KCR2 (0.53). The XRD and SEM analyses revealed that the alkaline etherification conditions did not alter the morphological and crystallographic properties, as well as the rheological behavior of the obtained derivatives. The amphiphilic character of the KCRs was investigated using a conductivity method which revealed that the molecular aggregation occurred above the critical aggregation concentration (CAC). Decreasing CAC values of 0.15% (KCR1), 0.11% (KCR2) and 0.08% (KCR3)with the degree of substitution (DS) were found. Furthermore, KCR’s derivatives greatly improved the stability of oil/water emulsions as the droplet size decreased with increasing DS. The derivative (KCR3) with higher DS, showed a greater amphiphilic character, and improved emulsifying power.

Dendrimeric micelles composed of polyamidoamine dendrimer-peptide-cholesterol conjugates as drug carriers for the treatment of melanoma and bacterial infection

Skin cancer is a serious health concern posing an economic burden. Phytochemicals isolated from plants have attracted the attention of researchers as potential therapeutic agents against skin cancer. Paclitaxel and curcumin are effective anticancer agents. However, their poor solubility in aqueous solutions results in low bioavailability, limiting their therapeutic applications. In this study, we developed dendrimeric micelles to encapsulate paclitaxel and curcumin for the treatment of melanoma. The antibacterial activity of curcumin-loaded dendrimeric micelles was evaluated. Dendrimeric micelles were prepared using PAMAM dendrimers conjugated with histidine-arginine dipeptides and cholesterol (PHRC). Different amounts of cholesterol (6 % or 23 %) were conjugated to the surface of PAMAM dendrimer generation 2 derivatives (PAMAM G2-HR) to evaluate the effects of cholesterol on the drug encapsulation efficiency and bioactivity. The critical aggregation concentration (CAC) value of PHRC6 and PHRC23 was 0.14 mg/mL and 0.09 mg/mL, respectively. The size of the dendrimeric micelles was confirmed using dynamic light scattering (DLS). Furthermore, the cytotoxicity of PHRC amphiphiles was measured in B16F10 melanoma cells. Both PHRC6 and PHRC23 were combined with TPGS to prepare functional mixed dendrimeric micelles, including PHRC6/TPGS and PHRC23/TPGS. The encapsulation efficiency was higher for curcumin than paclitaxel (80.2 % and 76.3 % for curcumin and 30.7 % and 38.2 % for paclitaxel in PHRC6/TPGS and PHRC23/TPGS, respectively). Based on these results, PHRC/TPGS dendrimeric micelles displayed a high potential for the nano-formulation of hydrophobic drugs and good bioavailability and bioactivity against skin cancer.

Artificial phosphatase upon premicellar nanoarchitectonics of lanthanum complexes with long-chained imidazole derivatives

Four novel long chain-containing tridentate imidazole derivatives (Ln, n = 1, 2, 3, 4) were synthesized for in situ formation of mononuclear lanthanum(III) complexes as artificial phosphodiesterases. These in-situ formed La(III) complexes (named LaLn) were used to catalyze the transesterification of 2-hydroxypropyl p-nitrophenyl phosphate (HPNP), a classic RNA model. Critical aggregation concentrations (CAC) were determined for the as-prepared tridentate imidazole derivatives as ligands and corresponding mixtures of equivalent ligand and La3+ ion with a mole rate of 1:1. It denotes that the introduction of La3+ ion increases the CAC values of imidazole derivatives by about 2 to 3 folds. Foaming test shows that the foam height is positively correlated with the length of hydrophobic chain. Transesterification of HPNP mediated by LaLn nanoarchitectonics indicates that the introducing of hydrophobic chain benefits rate enhancement, showing excess three orders of magnitude acceleration under physiological conditions (pH 7.0, 25 °C). Moreover, catalytic reactivities of these La(III) complexes increased along with the increase in chain length: LaL1 < LaL2 < LaL3 < LaL4, suggesting a positive correlation to hydrophobic chain length.

In Situ Supramolecular Polymerization via Organometallic-Catalyzed Macromolecular Metamorphosis

In Situ Supramolecular Polymerization via Organometallic-Catalyzed Macromolecular Metamorphosis

Amphiphilic N-oxyethylimidazolium calixarenes: Synthesis, micellar solubilization and molecular recognition of Adenine-containing nucleotides

For the first time amphiphilic calix[4]arenes bearing oxyethyl-imidazolium polar headgroups on one side and alkyl fragments on another side of the macrocyclic platform were synthesized. Critical aggregation concentration (CAC) value was estimated using two methods: (a) pyrene fluorescent probe; (b) fluorescein probe based on both its fluorescent and absorbance properties in micellar solution. All plots were adequately described by a sigmoidal Boltzmann type function. A comparative analysis of the CACs were detected by using two types of dyes was held. The system calixarene - fluorescein was found to different change the absorbance and colorimetric response toward various adenosines phosphates.

The Effect of Na-Based Salts on Critical Aggregation Concentration of Aqueous Peg-Sds Mixtures

Critical aggregation concentration (CAC) is a well-known parameter used to study the interactions between constituents in an aqueous mixture containing surfactant molecules. In this study, we have studied the effect of Na-based salts on CAC of aqueous binary mixture of neutral polymer, polyethylene glycol (PEG) and anionic surfactant, sodium dodecyl sulfate (SDS) using viscometric method. To estimate CAC, we have applied Jiang model to the measured viscosity data. From the estimated results, we observe that the value of CAC decreases with the increase of salt molecules in the mixtures. This behavior confirms that the presence of salt molecules favors the binding of SDS molecule to the PEG chain. Bangladesh Journal of Physics, 27(2), 39-48, December 2020

Novel aminocalixarene-modified polydiacetylene vesicles: Synthesis and naked-eye detection of ATP

For the first time amphiphilic calix[4]arene, bearing amine polar headgroups on one side and 10,12-pentacosadiynoic acid (PCDA) fragments on another side of the macrocyclic platform was synthesized. Critical aggregation concentration (CAC) value was estimated using pyrene fluorescent probe and corresponds to 0.027 mM. It was shown that embedding of synthesized macrocycle into the vesicles made from N-(2-aminoethyl)pentacosa-10,12-diynamide (AEPCDA) influences on the colloid stability and photopolymerisation degree of the AEPCDA lipid. The addition of calixarene was found to dramatically change the colorimetric response of photopolymerized PDA vesicles toward ATP. Therefore, obtained PDA-calixarene vesicles are promising colorimetric sensors for naked-eye qualitative analysis or even quantitative analysis of ATP. • New aminocalixarene with 10,12-pentacosadiynoic acid residues were synthesized. • PDA sensors were prepared by co-assembling amino-containing lipid with aminocalixarene. • PDA polymerization degree and stability of vesicle depends on the calixarene content. • Modified PDA changes its color in the presence of adenosine triphosphate salt.

Effect of chemical linkers of curcumin conjugated hyaluronic acid on nanoparticle properties and in vitro performances in various cancer cells

Chemical linkers play an important role in determining the physicochemical properties, stability and cytotoxic activities of nanoparticles for cancer treatment. Herein, curcumin (CUR) and hyaluronic acid (HA) conjugate nanoparticles with two different chemical linkers were compared in terms of their physicochemical properties and cytotoxicity to various cancer cells. CUR (10–50 mol%) was grafted onto HA backbones using ester (non-pH-sensitive) and hydrazone (pH-sensitive) bonds. All CUR-HA conjugates were able to self-assemble in aqueous medium to form nanoparticles. The conjugates with the hydrazone bonds showed lower critical aggregation concentration (CAC) values than those with the ester bonds. Particle sizes decreased when the loading of CUR increased from 10 mol% to 30 mol% but increased from 30 mol% to 50 mol% CUR. The 30 mol% CUR-HA nanoparticles with the hydrazone bonds (30ChH) showed the smallest particle size, which was slightly smaller than those with the ester bonds (30CeH). The stability of 30ChH was better than that of 30CeH, as observed by the unchanged particle size and zeta potential over 14 days. The in vitro CUR release from 30ChH at pH 7.4 was lower than that of 30CeH, suggesting that 30ChH would remain stable in blood circulation. The in vitro cytotoxicity study demonstrated that both CUR-HA conjugates significantly induced higher cytotoxicity and inhibition of cell proliferation than CUR solution in all cell lines tested (A549, PANC-1, HCT116 and Caco-2). In summary, the chemical linkers of the CUR-HA conjugates affected the physicochemical properties of the nanoparticles. The CUR-HA conjugates with pH-sensitive linkers showed greater stability and prevented drug release at physiological pH but showed high CUR release in the acidic environment of cancer cells, which indicates the potential for cancer therapy.

Insights into the interaction of Bovine Serum Albumin with Surface-Active Ionic Liquids in aqueous solution

The unique physicochemical properties of Ionic liquids (ILs) make them very desirable for biomedical applications, namely as surface active ionic liquids (SAILs). SAILs surface activity, intrinsically higher than conventional surfactants, allows them to enhance drug permeability across biomembranes and, thus, become better drug carriers than current solutions. To harvest the full potential of these materials, in-depth studies of ILs interactions with model proteins are necessary to understand the mechanisms controlling these biological processes. Albumin, a key protein of blood serum, is of particular relevance, namely in drug carrier applications. Thus, here we characterize the interaction of bovine serum albumin (BSA) with fluorinated ionic liquids which are SAILs that possess fluorous tags equal to or longer than four carbon atoms. Their impact on BSA stability and structure was evaluated using different biophysical techniques. Differential scanning fluorimetry (DSF) and calorimetry (DSC), as well as circular dichroism (CD), yielded insights on the stabilization and secondary structure of BSA upon incubation with the ILs. Binding dynamics of the interaction were studied by conductimetry and isothermal titration calorimetry (ITC), which give the values of critical aggregation concentration (CAC) of the BSA-IL complex formation, as well as thermodynamic parameters. The results presented herein support the hypothesis that BSA is stabilized and encapsulated in the presence of FILs. Thus, the FILs studied in this work have potential for uses in biomedical applications.

Investigation of Surfactant-Polymer Interactions Using Rheology and Surface Tension Measurements

The interactions between surfactants and a drag-reducing polymer were investigated at a low polymer concentration of 500 ppm, using measurements of the rheology and surface activity of surfactant-polymer solutions. A well-known drag-reducing polymer (anionic sodium carboxymethyl cellulose) and five different surfactants (two anionic, two non-ionic, and one zwitterionic) were selected for the interaction studies. The surfactant-polymer solutions were shear thinning in nature, and they followed the power law model. The interaction between the surfactant and polymer had a strong effect on the consistency index of the solution and a marginal effect on the flow behavior index. The surface tension versus surfactant concentration plots were interpreted in terms of the interactions between surfactant and polymer. The critical aggregation concentration (CAC) of the surfactant was estimated based on the surface tension and rheological data. The CAC values of the same charge surfactants as that of the polymer were found to be significantly higher than other combinations of surfactant and polymer, such as non-ionic surfactant/anionic polymer, and zwitterionic surfactant/anionic polymer.

Pullulan derivative with cationic and hydrophobic moieties as an appropriate macromolecule in the synthesis of nanoparticles for drug delivery

A new amphiphilic pullulan derivative (DBAP-PO) was obtained by grafting tertiary butyl amine and octanoyl groups on the pullulan backbone as cationic and hydrophobic moieties, respectively. The structural characteristics of the modified polymer were investigated by FT-IR and 1H and 13C NMR spectroscopy.The self-association ability in aqueous solution of DBAP-PO was studied by viscosity and fluorescence methods. The intrinsic viscosity of the polymer was determined by Wolf model. The critical aggregation concentration (CAC) value of 0.028 g/dL, determined by fluorescence measurements in the presence of pyrene, was confirmed by capillary viscosimetry and dynamic laser scattering (DLS). Dialysis method was used to demonstrate the capacity of the pullulan derivative to form spherical nanoparticles (d ~ 200 nm) loaded with model drug, sodium diclofenac (DF) (74% entrapment efficiency). The DF release was sustained and pH-dependent. In vitro cytotoxicity as well as morphological studies conducted on the human skin fibroblasts showed that DBAP-PO/DF nanoparticles do not exhibit cytotoxic effects at the pharmacologically relevant concentration of DF, maintaining the typical morphology of the cells.

Synthesis, characterization and potential application of hydrophobically modified carrageenan derivatives as pharmaceutical excipients

New amphiphilic derivatives of kappa-carrageenan (KC) were synthesized by hydrophobic modification with octyl chloride. Two different methods based on microwave and conventional heating were used. All KC derivatives (KCRs) were characterized by different techniques. The FT-IR and 1HNMR studies demonstrated that the octyl groups were effectively grafted onto KC backbone and confirmed that the derivative KCRMM, obtained by microwave heating, presented a higher degree of substitution (DS = 0.77) compared to KCRCM (0.45). The amphiphilic character investigation also revealed that KCRMM exhibited a lower critical aggregation concentration (CAC) value of 0.13% w/v than KCRCM (0.15%). Furthermore, KCRs greatly improved the stability of oil/water emulsions as the droplet size decreased with increasing DS. Unlike the conventional heating method, novel derivatives with a higher DS, greater amphiphilic character, and an improved emulsifying power were obtained by microwave-assisted synthesis. These derivatives could potentially be used in food, cosmetics, or as excipients in pharmaceutics.

New Amphiphilic Imidazolium/Benzimidazolium Calix[4]arene Derivatives: Synthesis, Aggregation Behavior and Decoration of DPPC Vesicles for Suzuki Coupling in Aqueous Media.

In this study, new types of amphiphilic calix[4]arene derivatives bearing N-alkyl/aryl imidazolium/benzimidazolium fragments were designed and synthesized by two step transformation: Regioselective Blanc chloromethylation of distal-di-O-butyl calix[4]arene and subsequent interaction with N-Substituted imidazole/benzimidazole. Critical aggregation concentration (CAC) values were estimated using pyrene fluorescent probe. Obtained macrocycles were found to form submicron particles with electrokinetic potential +44–+57 mV in aqueous solution. For the first time it was found that amphiphilic calixarene causes the fast transformation of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) multilamellar vesicles into unilamellar ones and leads to the ordering of the lipid in membranes at the molar calixarene/DPPC ratio more than 0.07. In situ complexes of calixarene aggregates with Pd(OAc)2 were found to be active in Suzuki–Miyaura coupling of 1-bromo-4-nitrobenzene with phenylboronic acid in water. It was shown that bulky N-substituents of heterocycle decrease the catalytic activity of the aggregates. These result can be assigned to the inhibition effect of Pd(II) complex in situ formation by bulky substituents located on the aggregate surface. Embedding of the most active palladium N-heterocyclic carbene (NHC) complex with methylimidazolium headgroups into DPPC vesicles enhances its catalytic activity in Suzuki–Miyaura coupling.

Structure-Dependent Antibacterial Activity of Amino Acid-Based Supramolecular Hydrogels

Bacterial infections are currently a major concern to human health. Amino acid-based supramolecular polymer hydrogels, which boast intrinsic antibacterial activity, are an important solution due to their good biocompatibility, cost effectiveness, and tunable structural properties. Herein, we reported three types of transparent supramolecular hydrogel with intrinsic antibacterial activity from self-assembly of commercially available Fmoc-tryptophan (Fmoc-W), Fmoc-methionine (Fmoc-M), and Fmoc-tyrosine (Fmoc-Y). The resulting hydrogels selectively inhibited the growth of Gram-positive bacteria. Moreover, the order of antibacterial activity was Fmoc-W hydrogel > Fmoc-M hydrogel > Fmoc-Y hydrogel. The critical aggregation concentration (CAC) values were found at concentrations of approximately 0.0293, 0.1172, and 0.4688 mM for Fmoc-W, Fmoc-M, and Fmoc-Y, respectively. Transmission electron microscope (TEM) images revealed rigid and aligned nanofibers for Fmoc-W hydrogel, while flexible nanofibers for Fmoc-M hydrogel and Fmoc-Y hydrogel. The results indicated that stronger aggregation capability of the gelator and the synergistic nanostructural morphology with more rigid and aligned nanofibers can lead to higher antibacterial activity of its corresponding hydrogel. In addition, the molecular arrangements of Fmoc-amino acids in the hydrogels may also contribute to their antibacterial activity. These results can guide the rational design, fabrication, and future application of other self-assembled amino acid-based hydrogels with excellent antibacterial activity.