Ai Kohata

Autonomous oscillations are fundamental nonequilibrium processes vital to life that contribute to homeostasis and robustness against noise from the external environment. Inspired by these biological systems, autonomously oscillating materials have been extensively developed to create lifelike objects. However, excitable dynamics, which are characteristic of threshold-triggered signaling in neurons, remain unexplored in the design of synthetic oscillatory materials despite their unique potential in signal processing to acquire adaptive functionalities. Herein, we report oil droplets on a water surface that exhibit autonomous oscillations with excitable dynamics driven by the assembly of two oppositely charged surfactants. The oscillation consists of a repetitive cycle of gradual expansion and rapid contraction of the interfacial areas of the oil droplets. Using AI-based image analysis, we quantified the dynamics and developed models to elucidate the underlying mechanism: the interfacial area gradually increased as surfactants accumulated at the oil–water interface and rapidly decreased upon threshold-triggered release of nanoemulsions, which effectively removed surfactants from the interface. Furthermore, we demonstrated that the oscillation is influenced by environmental fluctuations, introducing stochasticity into an otherwise deterministic excitable oscillator. This autonomous oscillatory system, analogous to the “integrate-and-fire” model of neural activity, provides a minimal physicochemical framework for designing adaptive liquid-like soft materials with complex excitable dynamics.

Polyethylene glycol (PEG) is a nonionic and highly water-soluble polymer, and PEGylation is widely used as a versatile chemical strategy to enhance the water solubility of otherwise poorly soluble molecules. The rational design of PEG-appended materials, therefore, requires an estimation of the PEG chain length necessary to achieve the desired level of solubility. Here, we investigated the relationship between the PEG chain length and the water solubility of PEG-appended molecules using a combination of experimental and computational approaches. We focused on monodisperse PEG with a discrete molecular weight, which enables us to identify the relationship between chain length and physicochemical properties, as represented by water solubility. Then, we designed a series of PEG-appended molecules bearing monodisperse PEG chains of varying lengths, and measured their water solubilities experimentally. In parallel, molecular dynamics-based alchemical free energy calculations yielded thermodynamic trends that reproduced the observed dependence of solubility on PEG chain length. Comparison of experimental and computational results showed that the calculations not only distinguished between water-soluble and insoluble PEG-appended molecules but also captured the solubility trends for moderately soluble species. These findings demonstrate the potential of molecular-dynamics-based free energy calculations for a priori prediction of the water solubility of PEG-appended molecules.

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.

Polyethylene glycol (PEG) is a nonionic and highly water-soluble polymer, and PEGylation is widely used as a versatile chemical strategy to enhance the water solubility of otherwise poorly soluble molecules. The rational design of PEG-appended materials, therefore, requires an estimation of the PEG chain length necessary to achieve the desired level of solubility. Here, we investigated the relationship between the PEG chain length and the water solubility of PEG-appended molecules using a combination of experimental and computational approaches. We focused on monodisperse PEG with a discrete molecular weight, which enables us to identify the relationship between chain length and physicochemical properties, as represented by water solubility. Then, we designed a series of PEG‑appended molecules bearing monodisperse PEG chains of varying lengths, and measured their water solubilities experimentally. In parallel, molecular dynamics-based alchemical free‑energy calculations yielded thermodynamic trends that reproduced the observed dependence of solubility on PEG chain length. Comparison of experimental and computational results showed that the calculations not only distinguished between water-soluble and insoluble PEG-appended molecules but also captured the solubility trends for moderately soluble species. These findings demonstrate the potential of molecular-dynamics-based free-energy calculations for a priori prediction of the water solubility of PEG-appended molecules.

By heating 1‐(ω‐azidoalkyl)‐2‐(2,2‐dihalovinyl)arenes in DMF, intramolecular Huisgen cycloaddition between the azido group and the 1,1‐dihalovinyl moiety proceeded smoothly to afford 5‐halo‐1,2,3‐triazole‐fused tricyclic benzocondensed compounds. Leveraging the remaining halogen groups, carbon‐chain extension via Mizoroki–Heck or Suzuki–Miyaura coupling reactions, followed by an intramolecular Friedel–Crafts reaction, furnished polycyclic systems incorporating fused triazole rings. Furthermore, transformation of the halogen groups into 2‐nitrobenzene derivatives via Suzuki–Miyaura cross‐coupling, followed by a Cadogan reaction using triphenylphosphine, provided a series of fluorescent pentacyclic compounds.

Perfluoroalkyl (R_F)-containing peptides exhibit higher cellular uptake efficiency and lower membrane affinity accounting for lower cytotoxicity, compared to R_H-containing counterparts.

Utilizing the unique properties of fluorine substitution is an effective strategy for constructing highly functional materials. Here, we synthesized a novel copolymer composed of [1.1.1]propellane and perfluoro(propyl vinyl ether) (PPVE), rich in alternating sequences. The spin-coated copolymer film was amorphous, and its surface exhibited an extremely low surface free energy (γ). The γ value was lower than that of polytetrafluoroethylene despite containing only 40 mol % PPVE units. This can be attributed to the cancellation of the C-F dipole moments by the entirely random orientation of the fluorine units.

Fast and direct permeation of drug molecules is crucial for effective biotherapeutics. Inspired by a recent finding that fluorous compounds disrupt the hydrogen-bonded network of water, we developed fluoro-crown ether phosphate ^CyclicFP-X. This compound acts as a fast cell-permeating agent, enabling direct delivery of various bioactive cargos (X) into cancer cells without endocytic entrapment. In contrast, its nonfluorinated cyclic analog (^CyclicP-X) failed to achieve cellular internalization. Although the acyclic fluorous analog ^AcyclicFP-X was internalized, this process occurred slowly owing to the involvement of an endocytic trapping pathway. Designed with a high fluorine density, ^CyclicFP-X exhibits compactness, polarity, and high-water solubility, facilitating lipid vesicle fusion by disrupting their hydration layers. Raman spectroscopy confirmed the generation of dangling -OH bonds upon addition of ^CyclicFP-OH to water. Furthermore, conjugating ^CyclicFP-X with fluorouracil (FU, an anticancer drug) via a reductively cleavable disulfide linker (^CyclicFP-SS-FU) demonstrated the general utility of fluoro-crown ether phosphate as a potent carrier for biotherapeutics.

Forming nano‐assemblies is essential for delivering DNA conjugates into cells, with the DNA density in the nano‐assembly playing an important role in determining the uptake efficiency. In this study, we developed a strategy for the facile synthesis of DNA strands bearing perfluoroalkyl (R_F) groups (R_F‐DNA conjugates) and investigated how they affect cellular uptake. An R_F‐DNA conjugate bearing a long R_F group at the DNA terminus forms a nano‐assembly with a high DNA density, which results in greatly enhanced cellular uptake. The uptake mechanism is mediated by clathrin‐dependent endocytosis. The use of R_F groups to densely assemble negatively charged DNA is a useful strategy for designing drug delivery carriers.