HYPOTHESIS:The incorporation of semi-fluorinated alkanes into phospholipid monolayers modulates their interfacial behavior and structural organization through fluorocarbon-hydrocarbon interactions. While prior studies demonstrated hierarchical self-assembly of a semi-fluorinated tetrablock in dipalmitoylphosphatidylcholine (DPPC) monolayers, it remains unclear how variations in the hydrocarbon chain length and molecular architecture of the semi-fluorinated alkane influence phase behavior and multilayer formation. We hypothesize that comparing diblocks and tetrablocks will reveal key structural determinants governing nanodomain formation and vertical stacking. EXPERIMENTS:We studied Langmuir monolayers composed of DPPC mixed with semi-fluorinated diblocks C10F21CmH2m+1 (F10Hm, m = 16 and 20) and tetrablocks ((C10F21CH2)(CmH2m+1)CH-CH(C10F21CH2)(CmH2m+1) (di(F10Hm), m = 16 and 20). Surface pressure-area and surface potential-area isotherms were recorded, and fluorescence and atomic force microscopies were employed to examine domain morphology. Additionally, compression-expansion cycles were performed to assess the stability of the observed assemblies. FINDINGS:All (F-alkyl)alkanes formed nanodomains at low surface pressures, which reorganized into vertically stacked multilayers upon compression. However, while di(F10H16) forms flower-like hierarchical structures at the phase boundary of DPPC, driven by chain-length compatibility and dipolar interactions, di(F10H20) shows more diffuse assemblies. We analyze the difference in assembling behavior between the two derivatives and highlight the critical role of hydrocarbon segments' length and symmetry in governing vertical segregation and domain morphology, thus offering new insight into the design of responsive interfacial materials.

The inverse electron-demand Diels–Alder (IEDDA) reaction is a powerful tool for bioorthogonal chemistry and materials engineering, yet its efficiency at structurally confined interfaces remains incompletely understood. In this study, we investigated the interfacial reactivity and monolayer behavior of a newly synthesized symmetric tetrazine derivative, C18-Tz-C18, in combination with a norbornene-functionalized amphiphile, C16-NCA, at the air–water interface. Langmuir monolayers of the binary system were fabricated via two distinct methods—vial pre-reaction and cospreading—and characterized using surface pressure–area and surface potential–area isotherms, along with fluorescence microscopy. The symmetric architecture of C18-Tz-C18 facilitated condensed phase formation and enhanced interfacial ordering compared to its previously reported monoalkylated counterpart. Notably, interfacial IEDDA reactions proceeded efficiently only when conducted in solution prior to film formation; spontaneous reactivity at the interface was markedly suppressed. Bayesian machine learning predicted similar second-order rate constants for C18-Tz-C18 and monoalkylated analogs in bulk solvents, suggesting that the observed differences arise from spatial constraints rather than intrinsic reactivity. These findings demonstrate the pivotal role of molecular symmetry and preorganization in governing surface-confined chemical ligation, offering design principles for functional interfacial systems in diagnostics, coatings, and drug delivery.

The adsorption of ionic surfactants and counter-ions at the air/water interface is important for many industrial processes. In the literature, the surface tension and surface potential data showed a complicated relationship that cannot be explained by the conventional models, either fully associated or fully dissociated models. Alternatively, ionic surfactants can have a partial association at the air/water interface. The degree of association varies with surface concentration and generates a distribution of counter-ions near the surface. This study reconciles the partial association and ionic distribution by a new quantification model. The model successfully described the surface tension and surface potential data for CTAB (cetyltrimethylammonium bromide). The model shows that the counter-ion association degree plays a deterministic role in limiting the adsorption capacity of ionic surfactants. The proposed structure is also consistent with X-ray surface reflectivity, in which CTAB demonstrated a condensed layer of counter-ion. The molecular insights can be extended to other ionic surfactants and oil/water interfaces.

Interactions between the sigma1 receptor agonist PRE-084 and various lipid monolayers, including dipalmitoylphosphatidylcholine (DPPC), DPP-ethanolamine (DPPE), DPP-glycerol (DPPG), DPP-serine (DPPS), palmitoylsphingomyelin (PSM), and cholesterol (Ch), were investigated to elucidate the effects of PRE-084 on membrane fluidity and stability. Their interactions with sigma1 receptor agonists have potential implications for neuroprotection, antidepressant, analgesic, and cognitive enhancement effects. In this study, we observed that the presence of PRE-084 in the subphase led to increased fluidity in DPPC and DPPE monolayers, whereas decreasing fluidity was observed in DPPG, DPPS, and PSM monolayers. The interaction of PRE-084 with Ch monolayers was found to be distinct from its interaction with other lipids. Fluorescence microscopy images revealed changes in the size and shape of liquid-condensed domains in the presence of PRE-084, supporting the notion of altered membrane fluidity. Our findings provide new insights into the interaction of PRE-084 with lipid monolayers and its potential implications for biological and membrane science.

The surface chemistry of the inverse electron-demand Diels-Alder (IEDDA) reaction at the air-water interface is elucidated. Tetrazine (C18-Tz) and norbornene derivatives (C16-NCA) were used as the reactants. Langmuir monolayers of C18-Tz, C16-NCA, and their binary mixtures were prepared on aqueous substrates. The surface properties were analyzed using the surface pressure (π)-molecular area (A) and surface potential (ΔV)-A isotherms, as well as fluorescence microscopy to monitor the progress of the reaction. First, to provide comparison data to evaluate the reaction on the surface, the two components were mixed in stock solutions of organic solvents for the IEDDA reaction. The Langmuir monolayer spread from the reaction solution was characterized as a function of the reaction time. In the subsequent experiments, the Langmuir monolayers were deposited onto the surface of the substrate solutions by spreading from separate stock solutions of C18-Tz and C16-NCA. The variation of the surface behavior of the monolayers with the molecular area, surface composition of the two components, compression speed of the monolayers, and the temperature was studied. We discuss the effects of the air phase in the reaction field on the reaction efficiency by comparing the results obtained from the two methods.

Tetrazine (Tz) is an emerging bioorthogonal ligand that is expected to have applications (e.g., bioimaging) in chemistry and chemical biology. In this review, we highlight the interactions of reduced tetrazine (rTz) derivatives insoluble in aqueous media with biological membrane constituents or their related lipids, such as dipalmitoyl-phosphatidylcholine, dipalmitoyl-phosphatidylethanolamine, dipalmitoyl-phosphatidylglycerol, palmitoyl-sphingomyelin, and cholesterol in the Langmuir monolayer state at the air–water interface. The two-component interaction was thermodynamically elucidated by measuring the surface pressure (π) and molecular area (A) isotherms. The monolayer miscibility between the two components was analyzed using the excess Gibbs energy of mixing and two-dimensional phase diagram. The phase behavior of the binary monolayers was studied using the Brewster angle, fluorescence, and atomic force microscopy. This study discusses the affinities of the rTz moieties for the hydrophilic groups of the lipids used.

An equation is developed to describe the surface potential at the diffuse plane for MgCl2 solutions. The equation, in combination with surface tension and surface potential data, was used to predict the Mg2+/Cl- distribution near the air/water surface of MIBC solution. It was found that net ionic adsorption has a negative charge, that it is more anionic than cationic. The result was contrasting to MIBC/NaCl system. The negative charge was confirmed by molecular simulations. Despite its small size, the divalent nature prevents Mg2+ from penetrating the anionic layer. The study provides important insights into the adsorption of electrolytes with unequal charges between anion and cation. One of the main applications of the study is predicting the bubble surface charge of foaming systems in the "hard" water. (C) 2021 Elsevier B.V. All rights reserved.

The change in surface potential was measured for NaI solutions. The modelled surface charge was then calculated and compared with molecular simulations. It was found that I- was enhanced at the air/water interface more than Na+. The result, which was confirmed by simulations, was opposite to the previous observation with NaCl. The trend is also consistent with anionic effects: larger and more polar anions adsorbed stronger at the air/water interface. The theoretical model was applied successfully to describe the changes for both systems, which are positive for NaG and negative for Nal, respectively. The combined results of the two systems also revealed that the self-ionization of pure water induced a positive surface charge at 16.9 mV. (C) 2019 Elsevier B.V. All rights reserved.

We found that monolayers of dipalmitoylphosphatidylcholine (DPPC) and semi-fluorinated tetrablock di( F 10 H 16) self-assemble to form a new type of large, complex flower-like patterns on the surface of water and on solid substrates. The hierarchical organization of these unusual self-assemblies was investigated using compression and surface potential isotherms, in situ fluorescence and Brewster angle microscopies, and atomic force microscopy after transfer.

Lipid rafts consisting mainly of sphingomyelin and cholesterol (Ch) on biomembrane surfaces are deeply related to cellular processes such as protein trafficking and signal transduction. During the processes, the raft microdomains affect the fluidty of biological membranes, which is controlled to large extents by Ch. In this paper, we have investigated the interaction between Ch and a semiflurinated alcohol (F6H9OH) from the aspect of a fluidty control using surface chemistry. The two-component Langmuir monolayer at the air-water interface was characterized by the surface pressure (π)-molecular area (A) and surface potential (ΔV)-A isotherms. The compressibility modulus and excess Gibbs free energy of mixing were calculated from the π-A isotherms. And also the two-dimensional phase diagram was constructed on the basis of phase transition pressures and monolayer collapse pressures. Furthermore, the phase behavior of binary monolayers was visualized with fluorescence microscopy (in situ) and atomic force microscopy (ex situ). The result here indicates a possibility of fluidity control of Ch-related membranes by arranging the fluorination degree of the constituent lipids.

The focus of this study is to elucidate lateral interactions between pentadecanol (H15OH) and (perfluorohexyl) nonanol (F6H9OH) at the air-water interface. The surface pressure (pi)- molecular area (A) and surface potential (Delta V)-A isotherms of the binary monolayer were measured as a function of mole fraction. The excess Gibbs free energy of mixing was calculated from the pi-A isotherms. In addition, a two-dimensional phase diagram of the system was constructed by analyzing the isotherm data. These results suggested miscibility between the two components. Furthermore, the addition of F6H9OH induced the fluidization and stabilization of H15OH monolayers at the low and high surface pressures, respectively. The phase behavior upon monolayer compression was visualized with in situ fluorescence microscopy and ex situ atomic force microscopy. A combination of both the microscopic images was successful in capturing the evidence of the two-component miscibility and phase transition at large F6H9OH mole fractions.

A series of alkanediyl-1-s-bis(dimethyltetradecylammonium bromide) (abbr. 14-s-14,2Br−) has been characterized in an aqueous medium at temperatures of 288.2, 298.2, and 308.2 K. Critical micelle concentration (cmc) of the surfactants was determined by measuring the surface tension and electrical conductivity as a function of concentrations. The micelle formation was elucidated thermodynamically from the results of electrical conductivity measurement. A steady-state fluorescence quenching and dynamic light scattering were performed to determine the aggregation number and the size of micelles, respectively. Furthermore, the surface potential (ΔV) was measured against surfactant concentrations to understand the condensing state of the adsorbed layer located at the air–water interface. The ΔV value directly can catch a vertical unequal shift of electric charges in the surface region above the bulk where the ΔV value is zero or electroneutrality is held. The results of ΔV measurements indicated that the adsorbed surfactants in the surface region were saturated in terms of amounts far below the cmc and that the vertical orientation of tetradecyl chains of 14-s-14,2Br− was improved by the longer spacers in a bending conformation towards the air.

The property of a newly synthesized tetrazine derivative comprised of double C18-saturated hydrocarbon chain (C18-rTz-C18) has been studied in situ at the air-water interface. C18-rTz-C18 or a gemini amphiphile contributes to restriction of its tetrazine moiety on the interface, which is expected to be used for bioimaging and analytical reagents. Herein, to understand lateral interactions between Tz and biomembrane constituents, we investigated the interfacial behavior of Langmuir monolayers composed of C18-rTz-C18 and biomembrane lipids such as DPPC, DPPG, DPPE, PSM, and Cholesterol (Ch). The lateral interaction of the binary monolayers was analyzed with the surface pressure (π)-molecular area (A) and surface potential (ΔV)-A isotherms. These thermodynamic data indicate that all of the two-components are miscible with each other. In particular, as opposed to the others, the monolayer stability of DPPE, which is a major constituent of the inner surface of cell membranes, is attenuated by the small-amount addition of C18-rTz-C18. This specific interaction implies the membrane destruction from the inside. The phase behavior during monolayer compression was visualized with Brewster angle microscopy (BAM), fluorescence microscopy (FM), and atomic force microscopy (AFM). The obtained morphologies exhibit a coexistence state of two different liquid-condensed domains derived from extra phospholipids and phospholipids-C18-rTz-C18 monolayers.

The interfacial behavior of binary monolayers of 1,1'-(1,ω-alkanediyl)-bispyridinium perfluorotetradecanecarboxylate (CnBP(FC14)2, n = 2, 6, or 10) and dipalmitoylphosphatidylcholine (DPPC) was studied using surface pressure (π)-area (A) and surface potential (ΔV)-A isotherm measurements and morphological observations. In a previous study, we showed that the spacer moieties of C2BP(FC14)2 and C6BP(FC14)2 are completely dissociated after spreading on 0.15 M NaCl, whereas the C10BP(FC14)2 spacer moieties do not dissociate in the monolayer state. However, in the present study, the ΔV-A isotherm indicated that the C10BP moiety partially dissociates in the presence of DPPC monolayers. The excess Gibbs free energy of mixing and two-dimensional phase diagrams suggest that CnBP(FC14)2 is miscible with DPPC monolayers and also has a fluidizing effect on DPPC monolayers. The phase behavior of the binary monolayers was observed with Brewster angle microscopy (BAM), fluorescence microscopy (FM), and atomic force microscopy (AFM). The dispersion mode of DPPC-rich domains by C10BP(FC14)2 is significantly different from those of the other CnBP(FC14)2 monolayers. These results suggest that the aliphatic chains in phospholipids control the dissociation of divalent spacers bound to fluorinated surfactants or amphiphiles.

We report the role of a spacer chain in gemini surfactants for solubilization of poor soluble compounds to the aqueous medium. Solubilization of n-alkylbenzenes into micellar solutions of alkanediyl-1,s-bis(dimethyltetradecylammonium bromide) (14-s-14,2Br−, s=2, 6, and 12) has been studied in the temperature range from 288.2 to 308.2K. The equilibrium concentrations of all the solubilizates are determined spectrophotometrically. The solubility of the solubilizates remains constant below the critical micelle concentration (cmc) and increases linearly with an increase in the surfactant concentration above the cmc. The hydrodynamic diameter of the micellar aggregates with or without the solubilizates is measured by means of dynamic light scattering (DLS). The enthalpy, entropy, and Gibbs energy changes for the solubilization of n-alkylbenzenes have been calculated to evaluate a driving force of a transfer of the solubilizates into the micelle. These results indicate that the driving force and solubilization site in the aggregates are changed depending on the spacer chain length of surfactants. Furthermore, the inner core of the solubilized aggregates has been investigated by Fourier transform infrared (FTIR) spectra and two-dimensional nuclear Overhauser effect spectroscopy (2-D NOESY).

The Hofmeister series has long been of both scientific and technological importance because it allows systematic predictions of the interaction between ions and molecules to be made. In this work, three different polyoxometalate (POM) anions and three different lipid monolayers were used to investigate the interplay between electrostatic and hydrophobic interactions. We used three Keggin-type POMs with different charges ([PW12O40](3-), [SiW12O40](4-), and [H2W12O40](6-)) to eliminate any effects of morphology and to focus on the effects of the charge and hydrophobicity of the POM anions. The POMs adsorb onto cationic lipid monolayers via electrostatic interactions, while hydrophobic interaction is the dominant factor for adsorption onto anionic lipid monolayers when charge neutralization is provided by cationic counterions. In contrast, the dominant interactions experienced by zwitterionic lipid monolayers can switch between electrostatic interactions for POMs with higher charge density and hydrophobic interactions for POMs with lower charge density. Furthermore, the dominant interaction could also switch as a function of lipid density. In the gas phase, lipid monolayers mostly interact with POMs through electrostatic interactions, and the strength of the influence of the POM varies in the order [PW12O40](3-) < [SiW12O40](4-) < [H2W12O40](6-). In contrast, the order switches to [PW12O40](3-) > [SiW12O40](4-) > [H2W12O40](6-) when the POM interacts with a compressed lipid monolayer (surface pressure = 40 mN/m), which reflects the Hofmeister series and the chaotropic nature of the POMs. Thus, hydrophobic interactions govern the penetration of the lipid monolayer for condensed cell membranes irrespective of the charge of the lipid. The observed switch implies the importance of the interplay between the electrostatic and hydrophobic interactions. Our findings provide new insight into the switchable binding modes of POMs for cell membranes with different lipid composition, density, and hydrophobicity, enabling the design of tailor-made POM-based materials for a new generation of antimicrobial agents.