Dipalmitoylphosphatidylcholine Monolayers Research Articles

Neural network-assisted model of interfacial fluids with explicit coarse-grained molecular structures.

Interfacial fluids are ubiquitous in systems ranging from biological membranes to chemical droplets and exhibit a complex behavior due to their nonlinear, multiphase, and multicomponent nature. The development of accurate coarse-grained (CG) models for such systems poses significant challenges, as these models must effectively capture the intricate many-body interactions, both inter- and intramolecular, arising from atomic-level phenomena, and account for the diverse density distributions and fluctuations at the interface. In this study, we use advanced machine learning techniques incorporating force matching and diffusion probabilistic models to construct a robust CG model of interfacial fluids. We evaluate our model through simulations in various settings, including the water-air interface, bulk decane, and dipalmitoylphosphatidylcholine monolayer membranes. Our results show that our CG model accurately reproduces the essential many-body and interfacial properties of interfacial fluids and proves effective across different CG mapping strategies. This work not only validates the utility of our model for multiscale simulations, but also lays the groundwork for future improvements in the simulation of complex interfacial systems.

Probing Deuteration-Induced Phase Separation in Supported Lipid Monolayers using Hyperspectral TERS Imaging.

In this study, we investigate the impact of deuteration on the formation of phase-separated domains in supported lipid monolayers using hyperspectral Tip-Enhanced Raman Spectroscopy (TERS) imaging. The intricate organization of biological membranes plays a crucial role in cellular functions. Various factors that influence domain formation have been identified in previous studies such as lipid tail length and cholesterol concentration. Deuterium labeling of lipids has proven useful for probing cellular structures and dynamics, but its impact on lipid phase separation remains underexplored. By examining 1:1 mixed monolayers of dipalmitoylphosphatidylcholine (DPPC) and deuterated DPPC on Au(111) surfaces, we reveal partial segregation of domains rich in deuterated and nondeuterated lipids. This study addresses a gap in knowledge by examining the impact of deuteration on lipid tail behavior, offering new insights into how even subtle structural modifications can influence phase behavior. Furthermore, it demonstrates that TERS can be a powerful, nondestructive, and label-free nanoanalytical tool for analyzing lipid membranes and advance the field of membrane biophysics.

Exploring the Use of a Lipopeptide in Dipalmitoylphosphatidylcholine Monolayers for Enhanced Detection of Glyphosate in Aqueous Environments.

The growing reliance on pesticides for pest management in agriculture highlights the need for new analytical methods to detect these substances in food and water. Our research introduces a SPRWG-(C18H37) lipopeptide (LP) as a functional analog of acetylcholinesterase (AChE) for glyphosate detection in environmental samples using phosphatidylcholine (PC) monolayers. This LP, containing hydrophilic amino acids linked to an 18-carbon aliphatic chain, alters lipid assembly properties, leading to a more flexible system. Changes included reduced molecular area and peak pressure in Langmuir adsorption isotherms. Small angle X-ray scattering (SAXS) and atomic force microscopy (AFM) analyses provided insights into the LP's structural organization within the membrane and its interaction with glyphosate (PNG). Structural and geometric parameters, as derived from in silico molecular dynamics simulations (MD), substantiated the impact of LP on the monolayer structure and the interaction with PNG. Notably, the presence of the LP and glyphosate increased charge transfer resistance, indicating strong adherence of the monolayer to the indium tin oxide (ITO) surface and effective pesticide interaction. A calibration curve for glyphosate concentration adjustment revealed a detection limit (LOD) of 24 nmol L-1, showcasing the high sensitivity of this electrochemical biosensor. This LOD is significantly lower than that of a similar colorimetric biosensor in aqueous media with a detection limit of approximately 0.3 μmol L-1. Such an improvement in sensitivity likely stems from adding a polar residue to the amino acid chain of the LP.

Antimicrobial and Anesthetic Niosomal Formulations Based on Amino Acid-Derived Surfactants.

This work proposes the development of new vesicular systems based on anesthetic compounds (lidocaine (LID) and capsaicin (CA)) and antimicrobial agents (amino acid-based surfactants from phenylalanine), with a focus on physicochemical characterization and the evaluation of antimicrobial and cytotoxic properties. Phenylalanine surfactants were characterized via high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR). Different niosomal systems based on capsaicin, lidocaine, cationic phenylalanine surfactants, and dipalmitoyl phosphatidylcholine (DPPC) were characterized in terms of size, polydispersion index (PI), zeta potential, and encapsulation efficiency using dynamic light scattering (DLS), transmitted light microscopy (TEM), and small-angle X-ray scattering (SAXS). Furthermore, the interaction of the pure compounds used to prepare the niosomal formulations with DPPC monolayers was determined using a Langmuir balance. The antibacterial activity of the vesicular systems and their biocompatibility were evaluated, and molecular docking studies were carried out to obtain information about the mechanism by which these compounds interact with bacteria. The stability and reduced size of the analyzed niosomal formulations demonstrate their potential in pharmaceutical applications. The nanosystems exhibit promising antimicrobial activity, marking a significant advancement in pharmaceutical delivery systems with dual therapeutic properties. The biocompatibility of some formulations underscores their viability. The proposed niosomal formulations could constitute an important advance in the pharmaceutical field, offering delivery systems for combined therapies thanks to the pharmacological properties of the individual components.

Cholesterol drives enantiospecific effects of ibuprofen in biomimetic membranes

The interaction between chiral drugs and biomimetic membranes is of interest in biophysical research and biotechnological applications. There is a belief that the membrane composition, particularly the presence of cholesterol, could play a pivotal role in determining enantiospecific effects of pharmaceuticals. Our study explores this topic focusing on the interaction of ibuprofen enantiomers (S- and R-IBP) with cholesterol-containing model membranes. The effects of S- and R-IBP at 20 mol% on bilayer mixtures of dipalmitoylphosphatidylcholine (DPPC) with 0, 10, 20 and 50 mol% cholesterol were investigated using circular dichroism and spin-label electron spin resonance. Morphological changes due to IBP enantiomers were studied with atomic force microscopy on supported cholesterol-containing DPPC monolayers. The results reveal that IBP isoforms significantly and equally interact with pure DPPC lipid assemblies. Cholesterol content, besides modifying the structure and the morphology of the membranes, triggers the drug enantioselectivity at 10 and 20 mol%, with the enantiomers differently adsorbing on membranes and perturbing them. The spectroscopic and the microscopic data indicate that IBP stereospecificity is markedly reduced at equimolar content of Chol mixed with DPPC. This study provides new insights into the role of cholesterol in modulating enantiospecific effects of IBP in lipid membranes.

A Sigma1 Receptor Agonist Alters Fluidity and Stability of Lipid Monolayers.

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 Interaction between Anesthetic Isoflurane and Model-Biomembrane Monolayer Using Simultaneous Quartz Crystal Microbalance (QCM) and Quartz Crystal Impedance (QCI) Methods.

The interaction between anesthetic Isoflurane (Iso) and model-biomembrane on the water surface has been investigated using quartz crystal microbalance (QCM) and quartz crystal impedance (QCI) methods. The model-biomembranes used were dipalmitoyl phosphatidyl choline (DPPC), DPPC-palmitic acid (PA) mixture (DPPC:PA = 8:2), DPPC-Alamethicin (Al) mixture (DPPC:Al = 39:1), and DPPC-β-Lactoglobulin (βLG) mixture (DPPC:βLG = 139:1) monolayers, respectively. The quartz crystal oscillator (QCO) was attached horizontally to each monolayer, and QCM and QCI measurements were performed simultaneously. It was found that Iso hydrate physisorbed on each monolayer/water interface from QCM and changed those interfacial viscosities from QCI. With an increase in Iso concentration, pure DPPC, DPPC-PA mixed, and DPPC-Al mixed monolayers showed a two-step process of Iso hydrate on both physisorption and viscosity, whereas it was a one-step for the DPPC-βLG mixed monolayer. The viscosity change in the DPPC-βLG mixed monolayer with the physisorption of Iso hydrate was much larger than that of other monolayers, in spite of the one-step process. From these results, the action mechanism of anesthetics and their relevance to the expression of anesthesia were discussed, based on the "release of interfacial hydrated water" hypothesis on the membrane/water interface.

Structural determinants of collapse by a monomolecular mimic of pulmonary surfactant at the physiological temperature.

Pulmonary surfactant forms a thin film on the liquid that lines the alveolar air-sacks. When compressed by the decreasing alveolar surface area during exhalation, the films avoid collapse from the air/water interface and reduce surface tension to exceptionally low levels. To define better the structure of compressed films that determines their susceptibility to collapse, we measured how cholesterol affects the structure and collapse of dipalmitoyl phosphatidylcholine (DPPC) monolayers at physiological temperatures. Grazing incidence X-ray diffraction (GIXD) and grazing incidence X-ray off-specular scattering (GIXOS) established the lateral and transverse structures of films on a Langmuir trough at a surface pressure of 45 mN m-1, just below the equilibrium spreading pressure at which collapse begins. Experiments with captive bubbles at a surface pressure of 51 mN m-1 measured how the steroid affects isobaric collapse. Mol fractions of the steroid (Xchol) at 0.05 removed the tilt by the acyl chains of DPPC, shifted the unit cell from centered rectangular to hexagonal, and dramatically decreased the long-range order. Higher Xchol produced no further change in diffraction, suggesting that cholesterol partitions into a coexisting disordered phase. Cholesterol had minimal effect on rates of collapse until Xchol reached 0.20. Our results demonstrate that the decreased coherence length, indicating conversion of positional order to short-range, is insufficient to make a condensed monolayer susceptible to collapse. Our findings suggest a two-step process by which cholesterol induces disorder. The steroid would first convert the film with crystalline chains to a hexatic phase before generating a fully disordered structure that is susceptible to collapse. These results lead to far-reaching consequences for formulation of animal-derived therapeutic surfactants. Our results suggest that removal of cholesterol from these preparations should be unnecessary below Xchol = 0.20.

Real-time topography inspection of DPPC monolayers using a surface-plasmon resonance sensor

This paper presents an alternative optical characterization of biosensors based on supported lipid monolayers (SLMs). Developing these biosensors requires precise thickness characterization of the films to understand their structure and dynamics. This paper proposes an optical technique to measure the thickness, optical properties, and location of a dipalmitoyl-phosphatidylcholine (DPPC) SLM on top of a metallic thin film. DPPC SLMs are of interest for biosensing applications, such as detecting pulmonary-related infections like SARS-CoV-2, Avian Influenza, and the H1N1 influenza virus. The monolayer was fabricated using the Langmuir–Blodgett technique, and the experimental characterization consisted of measuring the surface-plasmon resonance angle in the Kretschmann configuration. This technique provides an alternative option for real-time visual inspection and determination of the location and shape of DPPC monolayers in large areas. Therefore, it offers a useful tool for further developing SLM-based biosensors.

Numerical investigations of translocation characteristics of non-spherical silica nanoparticles across pulmonary surfactant monolayer under different respiratory states using coarse-grained molecular dynamics method

Understanding translocation characteristics of non-spherical silica nanoparticles (SiNPs) across pulmonary surfactant (PS) monolayer is of great significance for their applications in inhaled nanoparticles (NPs) drugs, as their shapes may impact drug delivery efficiency. Therefore, this study has performed coarse-grained molecular dynamics (CGMD) simulation to study the characteristics of SiNPs across the PS monolayer and adsorption of dipalmitoylphosphatidylcholine (DPPC) molecules. It is found that SiNPs smaller than 8 nm are more likely to cross the PS monolayer in expansion state than other states and crossing times required for ellipsoidal SiNPs are the shortest, and when SiNPs are in penetrating and embedding states, the number of DPPC molecules adsorbed by bulged-spherical SiNPs is the highest. In conclusion, ellipsoidal SiNPs have the strongest crossing ability and bulged-spherical SiNPs cause the greatest damage. Therefore, it is suggested to adopt ellipsoidal SiNPs and avoid bulged-spherical SiNPs when improving transportation efficiencies of spherical SiNP drug carriers.

Bioinspired nanoarchitectonics at the air-water interface to understand the interaction of lipids with a Europium-coordinated quinoline derivative

5SO3H-8-hydroxyquinoline coordinated to Europium (Eu-5SO3-HQ) was incorporated in biomembrane models using Langmuir monolayers. Dipalmitoyl phosphatidylcholine (DPPC) and dipalmitoyl phosphatidylserine (DPPS) were employed, representing mammalian cells and dioctadecyldimethylammonium bromide (DODAB) as a positively charged lipid to study the contrast with negatively charged lipids. Tensiometric, rheological and spectroscopic techniques were employed to characterize Eu-5SO3-HQ- lipid monolayer interactions. The complex condenses all the monolayer indicating interactions with the lipids' polar heads, but with distinctive effects on the mechanical and rheological properties. While the complex decreases the compression and elastic moduli of DPPC and DPPS monolayers, it increases for DODAB, also decreasing its lateral viscosity. Infrared spectroscopy shows that the interaction of Eu-5-SO3-HQ alters the ordering of the lipids' alkyl chains, impacting the monolayer's molecular packing. These results show that the interaction of Eu-5SO3-HQ with lipid monolayers at the air-water is modulated by the composition of the polar head, which can be supportive in the preparation of nanodevices for molecular probing.

Effect of partial O-methylation in dehydrodieugenol on its antitrypanosomal activity - correlation with the toxicity using cell membrane models

Biseugenol (1), a neolignan with antiprotozoal activity against Trypanosoma cruzi, was partially methylated, and the compound obtained – methyl biseugenol (2) – had its activity evaluated against the extracellular (trypomastigotes) and intracellular (amastigotes) forms of T. cruzi. It was observed that both compounds 1 and 2 exhibited similar effects against trypomastigotes (IC50 of 11.7 and 16.2 μM, respectively), whereas compound 2 displayed higher activity against amastigotes (IC50 = 8.2 μM) in comparison with biseugenol (IC50 = 15.4 μM). Additionally, reduced toxicity against NCTC cells for compound 2 was observed (CC50 > 200 μM), differently from compound 1 with CC50 = 58.0 μM. Aiming to understand better the molecular mechanism of the biological action of compound 2, the prodrug was incorporated into cellular membrane models constituted of Langmuir monolayers of the lipids dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylethanolamine (DPPE), dipalmitoylphosphatidylserine (DPPS), and dipalmitoylphosphatidylglycerol (DPPG). The lipid-drug interaction was inferred through tensiometry, surface potential, infrared spectroscopy (PM-IRRAS), and Brewster angle microscopy (BAM). The prodrug expanded DPPC and DPPG monolayers and condensed DPPE ones, as well as presented characteristic behaviors regarding the chemical structure of the lipid considering expansion-compression curves, surface potential-area isotherms, and stability of previously compressed monolayers to relevant-biological surface pressures. PM-IRRAS indicated a molecular disorder for DPPC and DPPS alkyl chains in the presence of the drug. BAM revealed the presence of domains in the DPPG and DPPE monolayers, which was probably induced by the prodrug. These data suggest, in general, that the lipid composition modulates the interaction of compound 2, whose results are expected to correlate to its trypanocidal activity, which involves the plasma membrane of T. cruzi as the primary target, i.e., the first barrier that the compound should encounter to interact with the microorganism.

Heterogeneous Nanostructures Cause Anomalous Diffusion in Lipid Monolayers.

The diffusion and mobility in biomembranes are crucial for various cell functions; however, the mechanisms involved in such processes remain ambiguous due to the complex membrane structures. Herein, we investigate how the heterogeneous nanostructures cause anomalous diffusion in dipalmitoylphosphatidylcholine (DPPC) monolayers. By identifying the existence of condensed nanodomains and clarifying their impact, our findings renew the understanding of the hydrodynamic description and the statistical feature of the diffusion in the monolayers. We find a universal characteristic of the multistage mean square displacement (MSD) with an intermediate crossover, signifying two membrane viscosities at different scales: the short-time scale describes the local fluidity and is independent of the nominal DPPC density, and the long-time scale represents the global continuous phase taking into account nanodomains and increases with DPPC density. The constant short-time viscosity reflects a dynamic equilibrium between the continuous fluid phase and the condensed nanodomains in the molecular scale. Notably, we observe an "anomalous yet Brownian" phenomenon exhibiting an unusual double-peaked displacement probability distribution (DPD), which is attributed to the net dipolar repulsive force from the heterogeneous nanodomains around the microdomains. The findings provide physical insights into the transport of membrane inclusions that underpin various biological functions and drug deliveries.

Incorporation of dehydrodieugenol, a neolignan isolated from Nectandra leucantha (Lauraceae), in lipid Langmuir monolayers as biomembrane models

Dehydrodieugenol, a neolignan isolated from the Brazilian plant Nectandra leucantha (Lauraceae) with reported antiprotozoal and anticancer activity, was incorporated in Langmuir monolayers of selected lipids as cell membrane models, aiming to comprehend its action mechanism at the molecular level. The interaction of this compound with the lipids dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylethanolamine (DPPE), dipalmitoylphosphatidylserine (DPPS), and dipalmitoylphosphatidylglycerol (DPPG) was inferred through tensiometry, infrared spectroscopy, and Brewster angle microscopy. The interactions had different effects depending on the chemical nature of the lipid polar head, with expansion for DPPC monolayers, condensation for DPPE, and expansion (at low surface pressures) followed by the overlap of the isotherms (at high surface pressure values) for DPPS and DPPG. Effects caused by dehydrodieugenol in the negatively charged lipids were distinctive, which was also reflected in the hysteresis assays, surface potential-area isotherms, and rheological measurements. Infrared spectroscopy indicated that the drug interaction with the monolayer affects not only the polar groups, but also the acyl lipid chains for all lipids. These results pointed to the fact that the interaction of the drug with lipid monolayers at the air-water interface is modulated by the lipid composition, mainly considering the polar head of the lipids, as well as the hydrophobicity of the lipids and the drug. As negatively charged lipids pointed to distinctive interaction, we believe this can be related to the antiprotozoal and anticancer properties of the compound.

Dominant hydrophobic interactions with β-glucan in nanoarchitectonics with mixed Langmuir monolayers of cholesterol/dipalmitoyl phosphatidyl choline.

The polysaccharide β-glucan, found in the cell wall of cereals such as wheat, oats, and barley, is believed to lower the concentration of bad cholesterol in humans, but the molecular-level mechanisms responsible for such an action are unknown. In this study, we use Langmuir monolayers of cholesterol and dipalmitoyl phosphatidyl choline (DPPC) as cell membrane models that are made to interact with β-glucan. Neat cholesterol and mixed cholesterol/DPPC monolayers were expanded upon incorporating β-glucan from the aqueous subphase. This incorporation was found to induce ordering in mixed monolayers and dehydration of the carbonyl group at higher cholesterol concentrations. These effects are attributed to hydrophobic interactions as identified with polarization-modulated infrared reflection-absorption spectroscopy. They correlate well with the hypothesis that cholesterol levels can be lowered by the formation of soluble fibers with β-glucan through hydrophobic interactions, blocking cholesterol absorption by the organism.

Spontaneous evolution of equilibrium morphology in phospholipid-cholesterol monolayers.

Competition between intradomain electrostatic repulsions and interdomain line tension leads to domain shape transitions in phase-separating lipid monolayers. The question remains if these morphologies are energy minima or are kinetically trapped metastable states. We show the reversible evolution of uniform width stripe domains from polydisperse semicircular domains in monolayers of dipalmitoylphosphatidylcholine (DPPC), hexadecanol (HD) or palmitic acid (PA), and dihydrocholesterol (DChol). The initial semicircular domains grow at a fixed 2:1 DPPC:HD (or PA) stoichiometry, depleting the liquid phase of HD, leaving behind a liquid enriched in DPPC and DChol. At higher surface pressures, the remaining DPPC precipitates onto existing domains, decreasing the ratio of line tension to the square of the dipole density difference, λ/μ2. Theory predicts that, as λ/μ2 decreases, circular domains reversibly transform to uniform width stripes as the minimum energy structure. Measuring the stripe width provides the first estimates of λ/μ2 at liquid condensed–liquid expanded phase coexistence.

In situ nonlinear optical spectroscopic study of the structural chirality in DPPC Langmuir monolayers at the air/water interface.

We conduct a molecular study on the structural chirality in Langmuir monolayers composed of dipalmitoylphosphatidylcholine (DPPC) using in situ nonlinear optical spectroscopies, including second harmonic generation (SHG) and sum frequency generation (SFG). Chiral SHG response is observed from L-DPPC monolayers at moderate surface pressures and almost vanishes at a high surface pressure. SFG spectra of L-DPPC monolayers show chiral features that can be assigned to the terminal CH3 groups and the CH2 groups attached to the chiral center atom. This means that these achiral moieties form chiral superstructures at the interface. Along with increasing surface pressure, the structural chirality of CH3 groups shows a similar trend as that of chiral SHG, but CH2 chirality increases monotonically. Furthermore, in a racemic DPPC monolayer with a moderate surface pressure, both chiral SHG and chiral SFG of CH3 groups are absent, whereas chiral SFG of CH2 groups is clearly present, indicating that L- and D-DPPC are diastereomers at the air/water interface and interfacial CH2 prefers a certain orientation regardless of the molecular handedness. A molecular mechanism is proposed to explain the origin of the structural chirality in DPPC monolayers.

Morphological Behavior of DPPC-DMPC Two-dimensional Mixed Monolayer on Water Surface by Dropping Method

We have investigated the morphology of dipalmitoyl phosphatidyl choline (DPPC)-dimyristoyl PC (DMPC) mixed monolayer formed on the water surface by the dropping method using surface tension measurement (STm), Brewster angle microscopy (BAM), and infrared external reflection spectroscopy (IERS). The limiting molecular area (A0) obtained by STm showed that the negative deviation at < mole fraction (xDMPC)= 0.4 whereas the positive deviation at > xDMPC =0.6 when DMPC was added to the DPPC monolayer. BAM images also showed that the condensed rigid monolayer at xDMPC < 0.4 changed to the expandable monolayer at xDMPC > 0.5. Moreover, IER spectra showed that the alkyl chains of both DPPC and DMPC molecules are in trans conformation in mixed monolayer at xDMPC =0.2 whereas gauche conformation existed at xDMPC = 0.8. Above findings have justified the transition of flexible gauche conformation alkyl chains of DMPC molecule into rigid trans conformation by the addition of DPPC molecule at xDMPC < 0.4 whereas alkyl chains retained flexible gauche conformation in both DPPC and DMPC molecules at xDMPC > 0.6.

Penetration of C60 into lung surfactant membranes: Molecular dynamics simulation studies

AbstractWe performed molecular dynamics simulations of the systems consisting of C60 molecules and dipalmitoylphosphatidylcholine (DPPC) monolayer membranes to study the penetration of C60 into lung surfactant (LS) membranes. The potential of mean force of the C60 penetration through the LS membrane was calculated as a function of the distance of a C60 molecule from the DPPC monolayer membrane. The free energy minimum of around 43 kcal/mol is located in the DPPC tail region, indicating that the C60 molecules can accumulate in the LS membrane region. The energy decomposition shows the main driving force of the C60 accumulation in the lipid tail region is the van der Waals interaction with the hydrocarbon tails of DPPC lipids. Finally, we observed that the water evaporation rate can be significantly enhanced by the accumulation of C60 molecules in the membrane tail region.

Novel cytotoxic amphiphilic nitro-compounds derived from a synthetic route for paraconic acids

A series of precursors for bioactive paraconic acids (PA) were synthesized and their cytotoxicity assessed on human cells in vitro. Two amphiphilic nitro-containing precursors, Nitro-C15-EED and the butanolide Nitro-C12-GBL, were cytotoxic at the micromolar scale, with higher activity on tumor HeLa cells than on HEK-293T of non-tumor origin. The structure of these molecules is simple but different from reported bioactive nitro compounds. Nitro-C12-GBL was generally more cytotoxic, but after short-term (2 h) exposure both compounds reached maximum cytotoxicity. At 72 h post-treatments of HeLa cells the final dose-response for Nitro-C12-GBL (LC50 = 21.9 µmol L−1) was close to that for Nitro-C15-EED (LC50 = 25.3 µmol L−1), corresponding to LC50s ~ 3–3.6 times lower than those on HEK-293T. Short-term treatments with 50 µmol L−1 of these compounds promoted comparable outcomes, reducing tumor cells viability up to 27–36% of the controls and preserving ~70% of HEK-293T viability at 72 h post-treatments. Reduced cytotoxicity was observed in cultures continuously exposed to the compounds for longer periods (24–72 h), especially on tumor cells, underlining short-term treatments as alternatives to antiproliferative strategies. Due to their amphiphilic nature, these compounds show spontaneous surface activity and adsorption onto Langmuir monolayers of dipalmitoyl phosphatidyl choline (DPPC), especially Nitro-C12-GBL. The effects on DPPC monolayers are indicative of a possible physiological action that depends on the interaction with the cell membranes. Coarse-grained molecular dynamics indicate that individualized molecules of Nitro-C15-EED and the less toxic PA precursors are susceptible to trapping into phospholipid films. In contrast, Nitro-C12-GBL consistently forms large aggregates with outward polar domains, which could favor interaction with phospholipid polar heads of biological membranes.