Hydrophobic Spacer Research Articles

Surface engineered novel cationic surfactants with enhanced surface adsorption for environmental applications

Gemini Cationic Surfactants (GCS) have garnered significant attention due to their distinctive molecular structure, featuring two hydrophilic head groups associated with a hydrophobic spacer. This distinctive configuration enables diverse applications across various fields. Hence, the current study introduces a novel series of GCSs, ethanediyl-1,2-bis[di(2-hydroxypropyl) alkylammonium] dibromide (Cn-C2-Cn[IsoPr(OH)2; n = 9, 12 and 14) and comprehensively explore their properties, highlighting their promising antimicrobial activity. The synthesis of GCSs was validated using 1H NMR and IR spectroscopy. Dynamic Light Scattering was employed to determine the dimensions of Gemini surfactant aggregates in aqueous solutions. Surface tension analysis determined critical concentrations of micelle (CMC), minimum surface area (Amin) and concentration of surface excess (Γmax). Physicochemical properties were assessed through conductivity and surface tension analyses in aqueous solutions. The CMC, Amin and Γmax values decrease as alkyl chain length extends. Surface tension data revealed strong adsorption of GCSs at interfaces. π values (mN/m) ranged from 36.7 (C14C2C14[Iso-Pr(OH)]2) to 45.3 (C9C2C9[Iso-Pr(OH)]2). Conductivity and surface tension measurements further characterized Gemini surfactants in aqueous environments at 298 K. The size of the micelle aggregates varied between C9C2C9[Iso-Pr(OH)]2 (1.2885 nm) and C14C2C14[Iso-Pr(OH)]2 (1.9210 nm), highlighting the impact of chain length on micelle size. Hence, the study highlights significant effect of the chain lengths on Gemini cationic surfactants’ self-assembly in dilute aqueous environments. Antimicrobial tests demonstrated significant activity of Cn-C2-Cn[IsoPr(OH)]2 GCSs at varying concentrations. Antimicrobial tests showed the significant antimicrobial potential of these GCS compounds, suggesting their potential and promising applications in medical, hygiene, environmental sanitation and advanced materials sectors.

Tuning Structural Organization via Molecular Design and Hierarchical Assembly to Develop Supramolecular Thermoresponsive Hydrogels.

The cellular microenvironment is composed of a dynamic hierarchical fibrillar architecture providing a variety of physical and bioactive signals to the surrounding cells. This dynamicity, although common in biology, is a challenge to control in synthetic matrices. Here, responsive synthetic supramolecular monomers were designed that are able to assemble into hierarchical fibrous structures, combining supramolecular fiber formation via hydrogen bonding interactions, with a temperature-responsive hydrophobic collapse, resulting in cross-linking and hydrogel formation. Therefore, amphiphilic molecules were synthesized, composed of a hydrogen bonding ureido-pyrimidinone (UPy) unit, a hydrophobic alkyl spacer, and a hydrophilic oligo(ethylene glycol) tail. The temperature responsive behavior was introduced by functionalizing these supramolecular amphiphiles with a relatively short poly(N-isopropylacrylamide) (PNIPAM) chain (M n ∼ 2.5 or 5.5 kg/mol). To precisely control the assembly of these monomers, the length of the alkyl spacer between the UPy moiety and PNIPAM was varied in length. A robust sol-gel transition, with the dodecyl UPy-PNIPAM molecule, was obtained, with a network elasticity enhancing over 2000 times upon heating above room temperature. The UPy-PNIPAM compounds with shorter alkyl spacers were already hydrogels at room temperature. The sol-gel transition of the dodecyl UPy-PNIPAM hydrogelator could be tuned by the incorporation of different UPy-functionalized monomers. Furthermore, we demonstrated the suitability of this system for microfluidic cell encapsulation through a convenient temperature sol-gel transition. Our results indicate that this novel thermoresponsive supramolecular system offers a modular platform to study and guide single-cell behavior.

Preparation and characterization of bionics Oleosomes with high loading efficiency: The enhancement of hydrophobic space and the effect of cholesterol

Liposomes (LIP) loaded with natural active ingredients have significant potential in the food industry. However, their low loading efficiency (LE) hampers the advancement of liposomal products. To improve the loading capacity of functional compounds, bionic oleosomes (BOLE) with a monolayer of phospholipid membranes and a glyceryl tricaprylate/caprate (GTCC) oil core have first been engineered by high-pressure homogenization. TEM revealed that the core of BOLE consists of GTCC instead of water, thereby extending the hydrophobic space. Steady-state fluorescence and active loading experiments confirmed that cholesterol (CH) detached from the phospholipid membrane and entered the oil core, where it repelled cannabidiol (CBD). Based on the extending hydrophobic space, CBD-BOLE was prepared and its LE was 3.13 times higher than CBD-LIP. The CBD-phospholipid ratio (CPR) of CBD-BOLE significantly improved at least 7.8 times. Meanwhile, the free radical scavenging activity of CBD was increased and cytotoxicity was reduced.

Piperidine and Pyridine Series Lead-Free Dion-Jacobson Phase Tin Perovskite Single Crystals and Their Applications for Field-Effect Transistors.

Two-dimensional (2D) organic-inorganic metal halide perovskites have gained immense attention as alternatives to three-dimensional (3D) perovskites in recent years. The hydrophobic spacers in the layered structure of 2D perovskites make them more moisture-resistant than 3D perovskites. Moreover, they exhibit unique anisotropic electrical transport properties due to a structural confinement effect. In this study, four lead-free Dion-Jacobson (DJ) Sn-based phase perovskite single crystals, 3AMPSnI4, 4AMPSnI4, 3AMPYSnI4, and 4AMPYSnI4 [AMP = (aminomethyl)-piperidinium, AMPY = (aminomethyl)pyridinium] are reported. Results reveal structural differences between them impacting the resulting optical properties. Namely, higher octahedron distortion results in a higher absorption edge. Density functional theory (DFT) is also performed to determine the trends in energy band diagrams, exciton binding energies, and formation energies due to structural differences among the four single crystals. Finally, a field-effect transistor (FET) based on 4AMPSnI4 is demonstrated with a respectable hole mobility of 0.57 cm2 V-1 s-1 requiring a low threshold voltage of only -2.5 V at a drain voltage of -40 V. To the best of our knowledge, this is the third DJ-phase perovskite FET reported to date.

Bismuth (Bi3+) based lead-free halide perovskitoid for light driven applications: A potential low-toxic alternative for lead (Pb2+)

Bismuth-based perovskite-like materials are recognised as feasible optoelectronic alternatives to lead-based perovskites. High toxicity and limited environmental stability of Pb-based perovskite are the principal hurdles for their practical use, whereas Bismuth (Bi3+) based materials exhibit relatively low toxicity. In this study, we fabricated (FPEA)BiI4 (FPEA = Fluorophenylethyl amine, as a hydrophobic aromatic spacer) and explored its compatibility in the field of photocatalysis and solar cells. UV–Vis, photoluminescence (PL) and time-correlated single photon counting (TCSPC) techniques were used to understand the optoelectronic properties of the material. These fabricated thin films were used towards toxic MBT remediation. Solar cells (in n-i-p configuration) were also fabricated using (FPEA)BiI4 and their photo conversion efficiency (PCE) was tested under AM1.5 illumination.

Boosting MA-based two-dimensional Ruddlesden-Popper perovskite solar cells by incorporating a binary spacer

Two-dimensional Ruddlesden-Popper (2DRP) perovskite exhibits excellent stability in perovskite solar cells (PSCs) due to introducing hydrophobic long-chain organic spacers. However, the poor charge transporting property of bulky organic cation spacers limits the performance of 2DRP PSCs. Inspired by the A-site cation alloying strategy in 3D perovskites, 2DRP perovskites with a binary spacer can promote charge transporting compared to the unary spacer counterparts. Herein, the superior MA-based 2DRP perovskite films with a binary spacer, including 3-guanidinopropanoic acid (GPA) and 4-fluorophenethylamine (FPEA) are realized. These films (GPA0.85FPEA0.15)2MA4Pb5I16 show good morphology, large grain size, decreased trap state density, and preferential orientation of the as-prepared film. Accordingly, the present 2DRP-based PSC with the binary spacer achieves a remarkable efficiency of 18.37% with a VOC of 1.15 V, a JSC of 20.13 mA cm−2, and an FF of 79.23%. To our knowledge, the PCE value should be the highest for binary spacer MA-based 2DRP (n ≤ 5) PSCs to date. Importantly, owing to the hydrophobic fluorine group of FPEA and the enhanced interlayer interaction by FPEA, the unencapsulated 2DRP PSCs based on binary spacers exhibit much excellent humidity stability and thermal stability than the unary spacer counterparts.

Cleavable Amphiphilic Biocides with Ester-Bearing Moieties: Aggregation Properties and Antibacterial Activity.

The rise of multidrug-resistant bacterial infections and the dwindling supply of newly approved antibiotics have emerged as a grave threat to public health. Toward the ever-growing necessity of the development of novel antimicrobial agents, herein, we synthesized a series of cationic amphiphilic biocides featuring two cationic headgroups separated by different hydrophobic spacers, accompanied by the inclusion of two lipophilic tails through cleavable ester functionality. The detailed aggregation properties offered by these biocides were investigated by small-angle neutron scattering (SANS) and conductivity. The critical micellar concentration of the biocides and the size and shape of the micellar aggregates differed with variation of pendant and spacer hydrophobicity. Furthermore, the aggregation number and size of the micelles were found to vary with changing concentration and temperature. These easily synthesized biocides exhibited potent antibacterial properties against various multidrug-resistant bacteria. The optimized biocides with minimum hematotoxicity and potent antibacterial activity against methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii exhibited rapid killing kinetics against planktonic bacteria. Also, these membrane-active agents were able to eradicate preformed biofilms. The enzymatic and acidic degradation profile further offered proof of gradual degradation. Collectively, these cleavable amphiphilic biocides demonstrated excellent potency for combating the multidrug-resistant bacterial infection.

Engineering of bioorthogonal polyzymes through polymer sidechain design.

Synthetic polymer scaffolds can encapsulate transition metal catalysts (TMCs) to provide bioorthogonal nanocatalysts. These 'polyzymes' catalyze the in situ generation of therapeutic agents without disrupting native biological processes. The design and modification of polymer scaffolds in these polyzymes can enhance the catalytic performance of TMCs in biological environments. In this study, we explore the hydrophobic design space of an oxanorborneneimide-based polymer by varying the length of its carbon side chain to engineer bioorthogonal polyzymes. Activity studies indicate that modulating the hydrophobicity of the polymer scaffold can be used to enhance the catalyst loading efficacy, catalytic activity, and serum stability of polyzymes. These findings provide insight into the structural elements contributing to improving polymeric nanocatalysts for a variety of applications.

Modulating efficacy and cytotoxicity of lipoamino fatty acid nucleic acid carriers using disulfide or hydrophobic spacers.

Double pH-responsive xenopeptides comprising polar ionizable succinoyl tetraethylene pentamine (Stp) motifs and lipophilic ionizable lipoamino fatty acids (LAFs) were recently found to efficiently transfect mRNA and pDNA at low doses. However, potency was often accompanied with cytotoxicity at higher doses. Insertion of bioreducible disulfide building blocks (ssbb) or non-reducible hydrophobic spacers between polar and apolar ionizable domains of LAF-Stp carriers should mitigate toxicity of xenopeptides. Carriers showed stable nucleic acid complexation and endosomal pH-dependent lytic activities, both of which were abolished after reductive cleavage of ssbb-containing carriers. For pDNA, U-shaped carriers with one Stp and two LAF units or bundle carriers with two Stps and four LAFs displayed highest potency. For mRNA, best transfection was achieved with bundle carriers with one Stp and four LAFs. Both the ssbb and hydrophobic spacer containing analogs displayed improved metabolic activity, reduced membrane damage, and improved cell growth. The ssbb carriers were most beneficial regarding living cell count and low apoptosis rates. Mechanistically, inserted spacers decelerated the transfection kinetics and altered the requirement of endosomal protonation. Overall, mRNA and pDNA carriers with improved biocompatibility have been designed, with their high potency illustrated in transfection of various cell lines including low passage number colon carcinoma cells.

Efficient synthesis of squalene by cytoplasmic-peroxisomal engineering and regulating lipid metabolism in Yarrowia lipolytica

Squalene, a high-value acyclic triterpenoid compound, is broadly used in the food and medical industries. Although the large acetyl-CoA pool and hydrophobic space of Yarrowia lipolytica are suitable for the accumulation of squalene, the current production level in Y. lipolytica is still not sufficient for industrial production. In this study, two rounds of multicopy integration of genes encoding key enzymes were performed to enhance squalene anabolic flux in the cytoplasm. Furthermore, the mevalonate pathway was imported into peroxisomes through the compartmentalization strategy, and the production of squalene was significantly increased. By augmenting the acetyl-CoA supply in peroxisomes and the cytoplasm, the squalene was boosted to 2549.1 mg/L. Finally, the squalene production reached 51.2 g/L by fed-batch fermentation in a 5-L bioreactor. This is the highest squalene production reported to date for microbial production, and this study lays the foundation for the synthesis of steroids and squalene derivatives.

Study on synthesis, surface activity and quantum chemical properties of anionic-nonionic Gemini surfactant

In this work, Gemini surfactants with different hydrophobic tails and spacer groups were designed and synthesized. The structures were verified by 1H NMR spectrum and mass spectrometry. The modulation of the experimental results of micellar thermodynamics and surface activity by the molecular structure has been thoroughly discussed and studied. Furthermore, the electrostatic potential results explain Gemini surfactants have a very efficient ability to reduce surface tension. The molecular polarity index (MPI) has been shown to be used to cost-effectively evaluate the surface activity of Gemini surfactants. It is hoped that the work will promote the structural design and industrial application of Gemini surfactants.

Bending behavior of the cysteinyl bolaamphiphile nanobelt assembly induced by the anisotropic disulfide bond formation

In this study, we explore how the covalent bonds linking individual building block molecules can substantially alter the suprastructure of molecular self-assembly. We focus on the role of covalent bonding within the self-assembled structures of a cysteinyl bolaamphiphile which consists of two cysteinyl motifs connected by a central hydrophobic heptyl chain spacer. The cysteinyl bolaamphiphile molecules self-assemble into a nanobelt structure with the creation of disulfide bonds during assembly, which prompts anisotropic molecular ordering and subsequent bending of the nanobelts. A series of control experiments revealed the twofold contribution of disulfide bonds: they facilitate the bending of the nanobelt assembly and the formation of longer assembled structures. Molecular dynamics simulation study confirms that the anisotropic distribution of disulfide bonds causes the bending of a nanobelt assembly. Moreover, the simulation and experimental studies demonstrated an increase in the nanobelt curvature as more disulfide bonds are generated. These results highlight the previously unappreciated influence of covalent bonds in causing macroscopic deformation of self-assembled structures.

Role of Gemini Surfactants with Variable Spacers and SiO2 Nanoparticles in ct-DNA Compaction and Applications toward In Vitro/In Vivo Gene Delivery.

Compaction of calf thymus DNA (ct-DNA) by two cationic gemini surfactants, 12-4-12 and 12-8-12, in the absence and presence of negatively charged SiO2 nanoparticles (NPs) (∼100 nm) has been explored using various techniques. 12-8-12 having a longer hydrophobic spacer induces a greater extent of ct-DNA compaction than 12-4-12, which becomes more efficient with SiO2 NPs. While 50% ct-DNA compaction in the presence of SiO2 NPs occurs at ∼77 nM of 12-8-12 and ∼130 nM of 12-4-12, but a conventional counterpart surfactant, DTAB, does it at its concentration as high as ∼7 μM. Time-resolved fluorescence anisotropy measurements show changes in the rotational dynamics of a fluorescent probe, DAPI, and helix segments in the condensed DNA. Fluorescence lifetime data and ethidium bromide exclusion assays reveal the binding sites of surfactants to ct-DNA. 12-8-12 with SiO2 NPs has shown the highest cell viability (≥90%) and least cell death in the human embryonic kidney (HEK) 293 cell lines in contrast to the cell viability of ≤80% for DTAB. These results show that 12-8-12 with SiO2 NPs has the highest time and dose-dependent cytotoxicity compared to 12-8-12 and 12-4-12 in the murine breast cancer 4T1 cell line. Fluorescence microscopy and flow cytometry are performed for in vitro cellular uptake of YOYO-1-labeled ct-DNA with surfactants and SiO2 NPs using 4T1 cells after 3 and 6 h incubations. The in vivo tumor accumulation studies are carried out using a real-time in vivo imaging system after intravenous injection of the samples into 4T1 tumor-bearing mice. 12-8-12 with SiO2 has delivered the highest amount of ct-DNA in cells and tumors in a time-dependent manner. Thus, the application of a gemini surfactant with a hydrophobic spacer and SiO2 NPs in compacting and delivering ct-DNA to the tumor is proven, warranting its further exploration in nucleic acid therapy for cancer treatment.

Syntheses and Structures of Arenethiolato Cobalt(II) Complexes Containing Acylamino Groups: Steric Effects of Bulky Ligands on Coordination and Geometry.

Bulky thiolato ligands have been developed for creating biomimetic model complexes of active sites in metalloenzymes. Herein, we report a series of di-ortho-substituted arenethiolato ligands containing bulky acylamino groups (RCONH; R = t-Bu-, (4-t-BuC6H4)3C-,{3,5-(Me2CH)2C6H3}3C-, and {3,5-(Me3Si)2C6H3}3C-) that were developed for biomimetics. Bulky hydrophobic substituents generate a hydrophobic space around the coordinating sulfur atom through the NHCO bond. This steric environment induces the formation of low-coordinate mononuclear thiolato Co(II) complexes. The well-positioned NHCO moieties in the hydrophobic space coordinate to the vacant sites of the cobalt center with different coordination modes, viz., the S,O-chelate of the carbonyl C═O or the S,N-chelate of the acylamido CON-. The solid (crystalline) and solution structures of the complexes were investigated in detail using single-crystal X-ray crystallography, 1H NMR, and absorption spectroscopic analyses. The spontaneous deprotonation of NHCO, which is commonly observed in metalloenzymes but requires a strong base in artificial systems, was simulated by forming a hydrophobic space in the ligand. This new ligand design strategy is advantageous for creating model complexes that have never been constructed artificially.

Hydrophobicity of 2-((8-hydroxyoctyl)oxy)ethyl-sulfanetrione in conducting solid polymer electrolyte boosting the electrochemical performance of lithium metal batteries

Rechargeable solid-state lithium metal battery (LMB) is an important next-generation energy storage technology. Anion chemistry of sulfonates plays a vital role in dictating the electrochemical performance of conducting solid polymer electrolytes (CSPEs). CSPE is a crucial need for LMB, although, simultaneously achieving high ionic conductivity and greater cycling performance in LMBs is a huge challenge. Herein, we design and synthesize new sulfonate anions 2-((8-hydroxyoctyl)oxy)ethyl-sulfanetrione (HOEST) and 2-(4-hydroxybutaoxy)ethane-sulfonate (HBES), and a series of CSPEs via coupling of these anions by tetraethyl orthosilicate for LMBs. HOEST-V CSPE consists of HOEST with PVDF polymeric matrix that delivers higher ionic conductivity (3.17 × 10−3 S cm−1) and outstanding cyclability (152 mAh g−1) at 25 °C for 1100 cycles. The excellent stability over 500 h of Li stripping/plating, high apparent diffusion coefficient (0.07177), and low activation energy (5.0251 Kj/mol) of HOEST-V impede the lithium dendritic growth for good compatibility with electrodes. The hydrophobic alkyl spacer of HOEST-V with anionic species and hydroxyl wing associated with ether spacer can dissociate and augment the Li+ ions mobility resulting from their intramolecular and intermolecular interactions, hydrogen bonding, and ion-dipole interaction. This strategy is promising and opens a new avenue for developing safe and high-performance CSPEs in future.

The design and synthesis of a long-side-chain-type anion exchange membrane with a hydrophilic spacer for alkaline fuel cells

Outstanding alkaline stability and high conductivity make side-chain-type anion exchange membranes (AEMs) become one of the ideal materials for AEM fuel cells (AEMFCs). However, the hydrophobic alkyl spacer between polymer backbones and cationic groups in AEMs limited their performance in AEMFCs. Herein, we demonstrated the design and synthesis of long-side-chain-type AEMs containing a hydrophilic ethylene oxide (EO) spacer using an appropriate EO-based monomer via click reaction. The obtained PPO-O-40 membrane with EO spacers showed higher hydroxide conductivity (52.1 mS cm−1 at 20 °C) than its counterpart with an alkyl spacer (PPO–C-40). The improved chemical stability of the PPO-O-x membrane was validated by an alkaline stability test for soaking in 1 M NaOH at 60 °C for 864 h. More importantly, an AEMFC assembled with the PPO-O-40 membrane displayed an outstanding peak power of 690 mW cm−2 at 60 °C under the optimal relative humidity of the anode. The short-term durability test observed a voltage decay rate of 6.1 mV h−1 during the continuous operation for 8 h at 200 mA cm−2. This work provides an alternative way to design highly conductive and durable side-chain-type AEMs containing a hydrophilic spacer for alkaline fuel cell application.

Molecular modeling and solubility of olopatadine hydrochloride polymorphs

Olopatadine hydrochloride is a selective H1 receptor antagonist used in ophthalmic solutions to treat the signs and symptoms of allergic conjunctivitis. This compound presents a phenomenon known as polymorphism, which can cause changes on physicochemical characteristics. Considering the worldwide regulatory requirements for drug registration and the complexity of the pharmacotechnical development of ophthalmic preparations, both supramolecular arrangements (carried out by the Hirshfeld surface) and theoretical calculations (through the quantum theory of atoms in molecules) led to understand the physicochemical properties of polymorphs I and II and possible differences in solubility. The supramolecular arrangement for both polymorphs consists of the chloride anion participating in strong NH ⋯ Cl and OH ⋯ Cl intermolecular interactions as well as two weak CH ⋯ Cl intermolecular interactions, which generate an ionic tetramer. The shape index HS shows the hydrophobic space, which is around the ionic tetramer formed by CH ⋯ π intermolecular interaction for form I as well as π ⋯ π stacking for form II. The supramolecular crystal arrangement provides an essential aspect of its solubility in drug polymorphs.

Anion-π interaction inside the polyanionic Mo132O372 cage with hydrophobic inner space.

In this paper, we provide experimental evidence to indicate that the polyanionic Mo132O372 cage with a hydrophobic inner nanospace has a unique capability to participate in anion-π interactions by showing a preference for electron-deficient mono-substituted benzenes over non-electron-deficient guests in inclusion.

Using host-guest interactions at the interface of quantum dots to load drug molecules for biocompatible, safe, and effective chemo-photodynamic therapy against cancer.

Combining photodynamic therapy (PDT) and chemotherapy (CHT) by loading an anti-cancer drug and a photosensitizer (PS) into the same delivery nanosystem has been proposed as an effective approach to achieve synergistic effects for a safe cancer treatment. However, exploring an ideal delivery nanosystem has been challenging, because the noncovalent interactions must be maintained between the multiple components to produce a stable yet responsive nanostructure that takes into account the encapsulation of drug molecules. We addressed this issue by engineering the interfacial interaction between Ag2S quantum dots (QDs) using a pillararene derivative to direct the co-self-assembly of the entire system. The high surface area-to-volume ratio of the Ag2S QDs provided ample hydrophobic space to accommodate the anti-drug molecule doxrubicine. Moreover, Ag2S QDs served as PSs triggered by 808 nm near-infrared (NIR) light and also as carriers for high-efficiency delivery of drug molecules to the tumor site. Drug release experiments showed smart drug release under the acidic microenvironments (pH 5.5) in tumor cells. Additionally, the Ag2S QDs demonstrated outstanding PDT ability under NIR light, as confirmed by extracellular and intracellular reactive oxygen species generation. Significant treatment efficacy of the chemo-photodynamic synergistic therapy for cancer using the co-delivery system was demonstrated via in vitro and in vivo studies. These findings suggest that our system offers intelligent control of CHT and PDT, which will provide a promising strategy for constructing hybrid systems with synergistic effects for advanced applications in biomedicine, catalysis, and optoelectronics.

Micelle-like Nanoassemblies of Short Peptides Create Antimicrobial Selectivity in a Conventional Antifungal Drug

The discovery of novel antibacterial drugs against infectious diseases has decreased over the past few decades because of their poor cost performance. In this study, we report that the nanoassembly of a short-peptide hydrogelator (P1) endowed novel antifungal selectivity to a conventional antifungal drug, amphotericin B (AmB), which expands its application spectrum. Clinical use of AmB is limited because of poor water solubility and poor selectivity in its toxicity, which often causes harmful effects on tissues. P1 was the low-molecular-weight hydrogelator (LMWHg) that showed low cytotoxicity and was enzymatically degraded. In general, an LMWHg entraps foreign hydrophobic molecules inside the hydrophobic space in the self-assembled body. P1 successfully solubilized AmB in water as a form of a nanocomplex (NC) that had a chain-like structure. The NCs showed remarkably low toxicity toward Saccharomyces cerevisiae as a model fungus when compared with free AmB, meaning that P1 suppressed the antifungal activity of AmB via coassembly. The suppressed antifungal activity of AmB recovered when P1 in the NCs was degraded by a protease to liberate AmB from the coassembly with P1. P1 at a high concentration formed a hydrogel incorporating AmB (AmB-P1 gel), in which the antifungal activity of AmB was suppressed as well as that in the NC. The coassembly with AmB affected the morphology of the P1 self-assembly. While S. cerevisiae that did not secrete proteases formed a colony on the AmB-P1 gel, Aspergillus oryzae that secreted proteases did not grow on the AmB-P1 gel at all, resulting in the selective killing of the fungus. Because some of malignant, infectious fungi secrete proteases, the coassembly strategy of conventional antifungal drugs with self-assembling molecules should lead to “drug repositioning” of approved drugs in the health and medical fields.