Self‐Assembly Behavior of Monodisperse PEG Amphiphiles Bearing Hydrophobic Units with Distinct Molecular Shapes in Water - PMC Skip to main content An official website of the United States government Here's how you know Here's how you know Official websites use .gov A .gov website belongs to an official government organization in the United States. Secure .gov websites use HTTPS A lock ( Lock Locked padlock icon ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites. Search Log in Dashboard Publications Account settings Log out Search… Search NCBI Primary site navigation Search Logged in as: Dashboard Publications Account settings Log in Search PMC Full-Text Archive Search in PMC Journal List User Guide PERMALINK Copy As a library, NLM provides access to scientific literature. Inclusion in an NLM database does not imply endorsement of, or agreement with, the contents by NLM or the National Institutes of Health. Learn more: PMC Disclaimer | PMC Copyright Notice ChemistryOpen . 2026 Apr 20;15(5):e70214. doi: 10.1002/open.70214 Search in PMC Search in PubMed View in NLM Catalog Add to search Self‐Assembly Behavior of Monodisperse PEG Amphiphiles Bearing Hydrophobic Units with Distinct Molecular Shapes in Water Ai Kohata Ai Kohata 1 School of Life Science and Technology, Institute of Science Tokyo, Yokohama‐shi, Kanagawa, Japan Find articles by Ai Kohata 1, ✉ , Rei Hamaguchi Rei Hamaguchi 1 School of Life Science and Technology, Institute of Science Tokyo, Yokohama‐shi, Kanagawa, Japan Find articles by Rei Hamaguchi 1 , Kazushi Kinbara Kazushi Kinbara 1 School of Life Science and Technology, Institute of Science Tokyo, Yokohama‐shi, Kanagawa, Japan 2 Research Center for Autonomous Systems Materialogy (ASMat), Institute of Integrated Research (IIR), Institute of Science Tokyo, Yokohama‐shi, Kanagawa, Japan Find articles by Kazushi Kinbara 1, 2, ✉ Author information Article notes Copyright and License information 1 School of Life Science and Technology, Institute of Science Tokyo, Yokohama‐shi, Kanagawa, Japan 2 Research Center for Autonomous Systems Materialogy (ASMat), Institute of Integrated Research (IIR), Institute of Science Tokyo, Yokohama‐shi, Kanagawa, Japan * Ai Kohata ( [email protected] ) | Kazushi Kinbara ( [email protected] ) ✉ Corresponding author. Revised 2026 Mar 31; Received 2026 Feb 18; Accepted 2026 Apr 3; Collection date 2026 May. © 2026 The Author(s). ChemistryOpen published by Wiley‐VCH GmbH This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. PMC Copyright notice PMCID: PMC13096572 PMID: 42010843 Abstract The shape of hydrophobic units on the self‐assembly of amphiphiles in pure water remains underexplored. In this work, three types of octaethylene glycol (OEG)–appended amphiphiles bearing propeller‐shaped, twisted, and planar hydrophobic units were synthesized. They formed different types of assemblies, such as liquid droplets, nanosheets, and supramolecular oligomers, suggesting the importance of molecular shape in designing the self‐assembly of amphiphiles in water. Keywords: amphiphile, PEG, self‐assembly, shape, supramolecular chemistry, surfactant Three types of PEG amphiphiles bearing hydrophobic units with distinct molecular shapes, such as twisted p ‐terphenyl, propeller‐shaped trityl, and planar pyrenyl groups, self‐assembled in pure water to form nanosheets, liquid droplets, and supramolecular oligomers, respectively. By using PEG with a defined molecular weight as a hydrophilic unit, we investigated how the shape of hydrophobic units affects the assembly of nonionic amphiphiles. 1. Introduction Self‐assembly of amphiphiles in aqueous media has long been an active area of research in materials science and biomedicine [ 1 , 2 ]. A wide variety of assembled objects, such as particles, droplets, tubes, or sheets ranging from nano‐ to micro‐scales, can be formed in water and exhibit distinctive intrinsic properties [ 3 , 4 ]. For designing such assemblies, the shape of the hydrophobic unit is crucial [ 5 , 6 , 7 , 8 ], because the hydrophobic effect dominates the assembly process in water [ 9 , 10 ]. Although the formation of assembled structures can be computationally predicted [ 11 ] by using a concept of the critical packing parameters [ 12 , 13 ], such methodologies often underestimate the role of hydrophobic parts [ 14 ] and directional intermolecular interactions in the assembly [ 15 ]. To date, the planar hydrophobic units were frequently employed together with functional groups that can induce directional forces such as hydrogen‐bonding and salt‐bridge interactions [ 16 , 17 , 18 , 19 ], whereas nonplanar units were rarely explored because their nonplanar configurations spatially hinder the intermolecular orientation and stacking, often resulting in the formation of disordered aggregates. In addition, the previously reported structures were often prepared in a mixture of organic solvents and water [ 20 , 21 , 22 , 23 , 24 ] because monomers cannot be fully dissolved in pure water. Therefore, the self‐assembled materials using nonplanar units formed in pure water, without organic cosolvents, remain underexplored [ 6 ]. In this work, we report the assembling behavior of octaethylene glycol (OEG)–appended nonionic amphiphiles bearing hydrophobic units with three different shapes in pure water. Poly(ethylene glycol) (PEG) is a widely used hydrophilic unit in nonionic monomers owing to its high water solubility [ 25 ]. We recently reported that the water solubility of PEG‐appended molecules increases with long ethylene glycol chains, using both experimental and computational approaches [ 26 ]. Because the water solubility governs the boundaries of dissolution, phase separation, and self‐assembly, the use of PEGs with defined lengths [ 27 , 28 , 29 ] can provide a structurally consistent framework for comparison, which would allow us to reveal the impact of the shape of hydrophobic units on their self‐assembly.We synthesized three types of OEG‐appended amphiphiles bearing hydrophobic units with similar numbers of carbon atoms with different shapes, including propeller‐shaped trityl (Trt, C 19 ; Trt OEG), twisted p ‐terphenyl ( p ‐terph, C 18 ; p ‐terph OEG), and planar pyrenyl (Pyr, C 16 ; Pyr OEG) groups (Figure 1 ). Under identical concentration and temperature, Trt OEG, p ‐terph OEG, and Pyr OEG formed liquid droplets, nanosheets, and supramolecular oligomers, respectively. FIGURE 1. Open in a new tab Molecular structures of octaethylene glycol (OEG) amphiphiles bearing a propeller‐shaped trityl (Trt) group ( Trt OEG), a twisted p ‐terphenyl ( p ‐terph) group ( p ‐terph OEG), and a planar pyrenyl (Pyr) group ( Pyr OEG). 2. Results and Discussion A series of OEG amphiphiles was synthesized according to a method analogous to the reported procedures [ 26 , 27 ]. In brief, OEG was reacted with 4‐hydroxy‐ p ‐terphenyl and 1‐hydroxypyrene, via Williamson ether synthesis, affording p ‐terph OEG and Pyr OEG, respectively. A substitution reaction between trityl chloride and OEG yielded Trt OEG. Three OEG amphiphiles thus obtained were diluted with ultrapure water at room temperature. First, to determine the concentration ranges at which the OEG amphiphiles start to aggregate, their critical aggregation concentration (CAC) was evaluated from the surface tension measurements (Figure S1). The CAC of Pyr OEG ([ Pyr OEG] CAC = 148 µM) was smaller than that of Trt OEG ([ Trt OEG] CAC = 361 µM) despite having fewer carbon atoms in the hydrophobic unit (C 16 ) than Trt OEG. In addition, the surface tension of the aqueous solution of Pyr OEG at 10 mM (51.7 ± 0.41mN/m) was higher than that of Trt OEG (45.5 ± 0.08 mN/m). These results indicate that Pyr OEG with a planar Pyr group can interact strongly with one another, possibly via π–π interactions. Notedly, the CAC of p ‐terph OEG could not be determined due to its poor water solubility (<1 µM) as previously reported [ 26 ]. This clear difference in CAC among Trt OEG, p ‐terph OEG, and Pyr OEG can be highly attributed to their shape rather than the number of carbon atoms. Next, the water solubility of three OEG amphiphiles was investigated by measuring the optical density (OD) of their bulk solutions ( λ = 560 nm). The aqueous solution of Trt OEG became turbid around 0.5 mM (Figure S2), while that of Pyr OEG remained transparent up to 1.7 M [ 26 ]. Since the fluorescent signal at 504 nm, originating from the pyrene excimer, emerged above the CAC of Pyr OEG (Figure S3), the formation of a pyrene dimer was plausible. However, the dimeric or oligomeric assemblies of Pyr OEG did not grow into sufficiently large assemblies to make the solution turbid. When the supernatant of the p ‐terph OEG suspension was analyzed by the absorption spectrometer, its concentration was found to be below the detection limit (<1 µM) [ 26 ]. Finally, we studied whether OEG amphiphiles form into any assemblies at the microscale. When a portion of the turbid Trt OEG suspension ([ Trt OEG] = 10 mM) was cast onto a glass substrate, interestingly, we observed micrometer‐scale spherical objects without internal substructures (Figures 2a and S4a). These microspheres coalesced in water (Supporting Movie S1), indicating they are phase‐separated liquid droplets composed of Trt OEG. On the other hand, in the suspension containing p ‐terph OEG, a white precipitate was observed (Figure 2b ), which was also visualized under a polarized optical microscope (Figure S5), suggesting the formation of highly ordered, crystalline‐like structures in water. Under identical conditions, no mesoscale structure was observed in the aqueous solution of Pyr OEG (Figures 2c and S4b). Accordingly, by dynamic light scattering (DLS), the moderate ACF values were confirmed in the aqueous solution and suspensions of Trt OEG ([ Trt OEG] = 0.1, 1, 10 mM; Figure 3a ), suggesting the formation of polydispersed particles ranging from nanometers to micrometers in size (Figure S6a). Meanwhile, p ‐terph OEG suspensions ([ p ‐terph OEG] = 0.1, 1, 10 mM) exhibited stronger values than those of Trt OEG (Figure 3b ), suggesting the presence of large aggregates (Figure S6b). In contrast, the ACF values were considerably low for Pyr OEG even at 2 M (Figure 3c ), which were comparable to those of PEG600 without hydrophobic units(Figure S7). These DLS results were consistent with the assemblies observed under optical microscopy and suggest that Pyr OEG plausibly forms oligomeric assemblies. It should be noted that, when the aqueous suspension of p ‐terph OEG was observed by transmission electron microscope (TEM), sheet‐like structures were visualized (Figure 4a ), whose thickness was further revealed to be as thin as 5 nm (Figure S8) by using atomic force microscope (AFM; Figure 4b ). FIGURE 2. Open in a new tab Optical micrographs of aqueous solutions of (a) Trt OEG, (b) p ‐terph OEG, and (c) Pyr OEG ([ Trt OEG] = [ p ‐terph OEG] = [ Pyr OEG] = 10 mM) at 25°C. FIGURE 3. Open in a new tab Normalized autocorrelation functions (ACFs) of (a) Trt OEG, (b) p ‐terph OEG ([ Trt OEG] = [ p ‐terph OEG] = 0.1, 1.0, 10 mM), and (c) Pyr OEG ([ Pyr OEG] = 0.1, 1.0, 10, 100 mM, 2 M) and its magnified graphs in water at 20°C. Error bars represent the standard deviations of three independent experiments ( n = 3). FIGURE 4. Open in a new tab (a) Transmission electron micrograph and (b) atomic force micrograph of p ‐terph OEG assemblies prepared from its aqueous suspension at 0.1 mM. As depicted in Figure 2 , Trt OEG, p ‐terph OEG, and Pyr OEG behaved quite differently in water: the formation of liquid droplets, stacked nanosheets, and assemblies with several molecules, respectively. Taking into account that three OEG amphiphiles carry hydrophobic units with a similar number of carbon atoms, these differences in assemblies should be attributed to their variations in molecular shape. p ‐terph OEG bearing a twisted p ‐terphenyl group, in which three benzene rings were connected in one‐dimensional manner with restricted motions, self‐assembled into stacked nanosheets and exhibited poor water solubility (<1 µM). On the other hand, Trt OEG formed phase‐separated liquid droplets with moderate water solubility (0.5 mM), possibly because the freely rotating conformations of a propeller‐shaped Trt group reduce intermolecular π−π interactions and increase the room for hydration of benzene rings. Interestingly, Pyr OEG bearing a planar four‐fused benzene motif self‐assembled into supramolecular oligomers around 150 µM ([ Pyr OEG] CAC ), but exhibited remarkably high water solubility (>1.7 M). Even though Pyr OEG was more likely to self‐assemble than Trt OEG ([ Trt OEG] CAC = 360 µM), Pyr OEG exhibited higher water solubility than Trt OEG, possibly because the pyrene unit formed a stable assembly surrounded by hydrophilic PEG units, which prevented Pyr OEG molecules from forming polymeric assemblies. 3. Conclusion In conclusion, we investigated the self‐assembly of OEG amphiphiles with three different hydrophobic units using a length‐defined PEG chain in pure water. The shapes of hydrophobic units significantly affected not only their water solubility ([ p ‐terph OEG] < 0.1 µM, [ Trt OEG] = 0.5 mM, [ Pyr OEG] > 1.7 M), but also the self‐assembly behaviors, affording various assemblies such as nanosheets, liquid droplets, and supramolecular oligomers. As demonstrated in this study, the shape of amphiphilic monomers should be considered an important factor in designing and producing functional structures in water, where the intermolecular interactions are dominated by strong hydrophobic effects, complicating the structural prediction of self‐assembly. Supporting Information Additional supporting information can be found online in the Supporting Information section. Funding This work was supported by the Ministry of Education, Culture, Sports, Science, and Technology of Japan (JP23K17363, JP25K18070). Conflicts of Interest The authors declare no conflicts of interest. Supporting information Supplementary Material OPEN-15-e70214-s001.zip (14.4MB, zip) Acknowledgments The authors thank Materials Analysis Division, Core Facility Center, Institute of Science Tokyo, for transmission electron microscopy, and Facility Station Division, Core Facility Center, Research Infrastructure Management Center, Institute of Science Tokyo, for atomic force microscopy and surface tension measurements. This work was supported by Grant‐in‐Aid for Challenging Research (Pioneering) (JP23K17363 to Kazushi Kinbara) and Grant‐in‐Aid for Young Scientists (25K18070 to Ai Kohata). Contributor Information Ai Kohata, Email: [email protected]. Kazushi Kinbara, Email: [email protected]. Data Availability Statement The data that support the findings of this study are available from the corresponding author upon reasonable request. References 1. Aida T., Meijer E. W., and Stupp S. I., “Functional Supramolecular Polymers,” Science 335 (2012): 813–817. 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