Classical Molecular Dynamics Simulation of Glyonic Liquids: Structural Insights and Relation to Conductive Properties.

Rhamnolipids are biosurfactants that have obtained wide industrial and environmental interests with their biodegradability and great surface activity. Besides their important roles as surfactants, they are found to function as a new type of glycolipid-based protic ionic liquids (ILs)─glyonic liquids (GLs). GLs are reported to have impressive physicochemical properties, especially superionic conductivity, and it was reported in experiments that specific ion selections and the fraction of water content have a strong effect on the conductivity. Also, the shape of the conductivity curve as a function of water fraction in GLs is interesting with a sharp increase first and a long plateau. We related the conductivities to the three-dimensional (3D) networks composed of -OH inside the GLs utilizing classical molecular dynamics (MD) simulations. The amount and size of these networks vary with both ion species and water fractions. Before reaching the first hydration layer, the -OH networks with higher projection/box length ratios indicate better conductivity; after reaching the first hydration layer and forming continuous structures, the conductivity retains with more water molecules participating in the continuous networks. Therefore, networks are found to be a qualitative predictor of actual conductivity. This is explained by the analysis of the atomic structures, including radial distribution function, fraction free volume, anion conformations, and hydrogen bond occupancies, of GLs and their water mixtures under different chemical conditions.

Layered supramolecular hydrogels from thioglycosides.

Low molecular weight hydrogels are made of small molecules that aggregate via noncovalent interactions. Here, comprehensive characterization of the physical and chemical properties of hydrogels made from thioglycolipids of the disaccharides lactose and cellobiose with simple alkyl chains is reported. While thiolactoside hydrogels are robust, thiocellobioside gels are metastable, precipitating over time into fibrous crystals that can be entangled to create pseudo-hydrogels. Rheology confirms the viscoelastic solid nature of these hydrogels with storage moduli ranging from 10-600 kPa. Additionally, thiolactoside hydrogels are thixotropic which is a desirable property for many potential applications. Freeze-fracture electron microscopy of xerogels shows layers of stacked sheets that are entangled into networks. These structures are unique compared to the fibers or ribbons typically reported for hydrogels. Differential scanning calorimetry provides gel-to-liquid phase transition temperatures ranging from 30 to 80 °C. Prodan fluorescence spectroscopy allows assignment of phase transitions in the gels and other lyotropic phases of high concentration samples. Phase diagrams are estimated for all hydrogels at 1-10 wt% from 5 to ≥ 80 °C. These hydrogels represent a series of interesting materials with unique properties that make them attractive for numerous potential applications.

Interfacial and Solution Aggregation Behavior of a Series of Bioinspired Rhamnolipid Congeners Rha-C14-Cx (x = 6, 8, 10, 12, 14).

Rhamnolipids are glycolipids produced by microorganisms with outstanding surfactant properties. They are a class of biosurfactants that are potential candidates for biodegradable and nontoxic replacements of current specialty synthetic surfactants. Building on our previous efforts in developing an efficient and practical chemical methodology to synthesize rhamnolipids allows us to now explore the tunability of rhamnolipid properties. Here, we explore the impact on solution self-assembly and adsorption at the air/water interface of symmetry of the two lipid tails for diastereomeric mixtures of a series of monorhamnolipids of the generic structure Rha-C14-Cx. Surface activity of the anionic forms of these molecules at pH 8 is described by surface tensiometry. Characteristics of their aggregation behavior in aqueous solutions including hydrodynamic radius, aggregation number, and aggregate morphology are determined using dynamic light scattering and time-resolved fluorescence quenching spectroscopy. The solution aggregation behavior of this series is found to unexpectedly vary in a nonmonotonic fashion. This is explained by molecular structural attributes of each series member that result in differences in the respective intermolecular interactions of various parts of these surfactants.

Thermally Induced Formation of HF4TCNQ- in F4TCNQ-Doped Regioregular P3HT.

The prototypical system for understanding doping in solution-processed organic electronics has been poly(3-hexylthiophene) (P3HT) p-doped with 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ). Multiple charge-transfer states, defined by the fraction of electron transfer to F4TCNQ, are known to coexist and are dependent on polymer molecular weight, crystallinity, and processing. Less well-understood is the loss of conductivity after thermal annealing of these materials. Specifically, in thermoelectrics, F4TCNQ-doped regioregular (rr) P3HT exhibits significant conductivity losses at temperatures lower than other thiophene-based polymers. Through detailed spectroscopic investigation of progressively heated P3HT films coprocessed with F4TCNQ, we demonstrate that this diminished conductivity is due to formation of the nonchromophoric, weak dopant HF4TCNQ-. This species is likely formed through hydrogen abstraction from the α aliphatic carbon of the hexyl chain at the 3-position of thiophene rings of rr-P3HT. This reaction is eliminated for polymers with ethylene glycol-containing side chains, which retain conductivity at higher operating temperatures. In total, these results provide a critical materials design guideline for organic electronics.

FTIR Spectroelectrochemistry of F4TCNQ Reduction Products and Their Protonated Forms.

The tetrafluorinated derivative of 7,7,8,8-tetracyanoquinodimethane (TCNQ), 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ), is of interest for charge transfer complex formation and as a p-dopant in organic electronic materials. Fourier transform infrared (FTIR) spectroscopy is commonly employed to understand the redox properties of F4TCNQ in the matrix of interest; specifically, the ν(C≡N) region of the F4TCNQ spectrum is exquisitely sensitive to the nature of the charge transfer between F4TCNQ and its matrix. However, little work has been done to understand how these vibrational modes change in the presence of possible acid/base chemistry. Here, FTIR spectroelectrochemistry is coupled with density functional theory spectral simulation for study of the electrochemically generated F4TCNQ radical anion and dianion species and their protonation products with acids. Vibrational modes of HF4TCNQ-, formed by proton-coupled electron transfer, are identified, and we demonstrate that this species is readily formed by strong acids, such as trifluoroacetic acid, and to a lesser extent, by weak acids, such as water. The implications of this chemistry for use of F4TCNQ as a p-dopant in organic electronic materials is discussed.

A Classical Molecular Dynamics Simulation Study of Interfacial and Bulk Solution Aggregation Properties of Dirhamnolipids.

The rhamnolipids are a unique class of biosurfactants produced by the bacteria Pseudomonas aeruginosa. These molecules display a high level of surface activity as well as biodegradability. In this study nonionic dirhamnolipid was investigated by utilizing molecular dynamics simulation at the air-water interface as well as in bulk water. Detailed structural analysis is presented for both the interfacial simulations and the simulations in solution. A systematic comparison was made between our previous work on the monorhamnolipid at the air-water interface and in bulk water. The presence of a second rhamnose group in dirhamnolipid did not show any significant change in the aggregation at the air-water interface. An increase in the molecular weight resulted in the larger surface area per monomer for dirhamnolipid compared to monorhamnolipid at the air-water interface. However, aggregation of dirhamnolipid in bulk water was affected by the presence of a second rhamnose group. Dirhamnolipid aggregates into micellar structure around ∼N22 which was lower than the monorhamnolipid aggregation number ∼N40. The hydrophobic component of the dirhamnolipid was enhanced to balance the higher hydrophilic component. An increase in alkyl chain length has shown that the enhanced hydrophobic component supports the formation of micellar aggregates up to ∼N30 and above, which was not observed in dirhamnolipid with a shorter alkyl chain length.

Biodegradability and Toxicity of Cellobiosides and Melibiosides.

In 2014, almost 16 million tons of surfactants were used globally for cleaning and industrial applications. As a result, massive quantities disperse into environmental compartments every day. There is great market interest in developing highly biodegradable, less-toxic, and renewable alternatives to currently used petroleum-based surfactants. Glycolipid surfactants, composed of a sugar head-group and lipid tail, are effective surfactants and emulsifiers with a high tolerance to electrolytes and are easily tailored to address specific needs. The green synthesis and surfactant characteristics of a suite of cellobiosides and melibiosides were recently described. The biodegradability and toxicity of 1°-alkyl-O-cellobiosides, 2°-alkyl-O-cellobiosides, and 1°-alkyl-O-melibiosides with straight-chain alkyl tails of 8, 10, and 12 are reported in this study. Biodegradability was assessed by quantifying mineralization (CO2 evolution). All of the glycosides were inherently biodegradable and most were readily biodegradable according to OECD and EPA definitions. The Microtox acute toxicity assay showed both chain length and head group had significant effects on toxicity, but most of the molecules were practically non-toxic according to EPA definitions with EC50 values > 100 mg L-1. Cytotoxicity to human lung (H1299) and keratinocyte cell lines (HaCaT) was measured by xCELLigence and MTS assays. Cytotoxicity values were comparable to similar glycosides previously reported. IC50 values were determined but, in general, exceeded surfactant concentrations that are found in the environment. These data demonstrate the promising nature of these molecules as green alternatives to petrochemical surfactants.

Direct Nanoscopic Measurement of Laminar Slip Flow Penetration of Deformable Polymer Brush Surfaces: Synergistic Effect of Grafting Density and Solvent Quality.

A detailed quantitative nanoscopic description of soft surfaces under dynamic flow is lacking, despite its importance. To better understand the role of surface texture in nanoscopic mass transport in complex media, we used Förster resonance energy transfer in combination with total internal reflectance fluorescence microscopy (FRET-TIRFM) to directly measure laminar slip flow penetration depth (slip length) on poly(N-isopropylacrylamide) (pNIPAM) thin films (50-110 nm) of different grafting densities (0.60, 0.38, and 0.27 chain/nm2) in solvents of different qualities created via cononsolvency in situ. Nontrivial synergistic interplay of grafting density and solvent quality on slip length was observed. Slip lengths are typically tens of nm (40-100 nm), increasing and then reaching a plateau with applied linear flow velocity (192-2,952 µm/s) regardless of experimental system. Slip length was systematically larger for lower density films, but the effect of grafting density was more significant in a good solvent than a poor solvent. Interestingly, however, the stagnant film thickness (polymer swollen thickness minus the slip length) collapsed to almost a singular value for a given grafting density regardless of solvent quality, likely suggesting a large gradient of segmental mobility at nonequilibrium. Moreover, we found that slip flow penetrates into soft pNIPAM surfaces more deeply in a good solvent than in a poor solvent and that this behavior was general and independent of grafting density. This behavior is counter to the notion that less interaction between a fluid (probe) and a solid surface promotes slip.

Biodegradability and toxicity of monorhamnolipid biosurfactant diastereomers.

Synthetic monorhamnolipids differ from biologically produced material because they are produced as single congeners, depending on the ß-hydroxyalkanoic acid used during synthesis. Each congener is produced as one of four possible diastereomers resulting from two chiral centers at the carbinols of the lipid tails [(R,R), (R,S), (S,R) and (S,S)]. We compare the biodegradability (CO2 respirometry), acute toxicity (Microtox assay), embryo toxicity (Zebrafish assay), and cytotoxicity (xCELLigence and MTS assays) of synthetic rhamnosyl-ß-hydroxydecanoyl-ß-hydroxydecanoate (Rha-C10-C10) monorhamnolipids against biosynthesized monorhamnolipid mixtures (bio-mRL). All Rha-C10-C10 diastereomers and bio-mRL were inherently biodegradable ranging from 34 to 92% mineralized. The Microtox assay showed all Rha-C10-C10 diastereomers and bio-mRL are slightly toxic according to the US EPA ecotoxicity categories with 5 min EC50 values ranging from 39.6 to 87.5 µM. The zebrafish assay showed that of 22 developmental endpoints tested, only mortality was observed at 120 h post fertilization; all Rha-C10-C10 diastereomers and bio-mRL caused significant mortality at 640 µM, except the Rha-C10-C10 (R,R) which showed no developmental effects. xCELLigence and MTS showed IC50 values ranging from 103.4 to 191.1 µM for human lung cell line H1299 after 72 h exposure. These data provide key information regarding Rha-C10-C10 diastereomers that is pertinent when considering potential applications.

Chemical Additives Enable Native Mass Spectrometry Measurement of Membrane Protein Oligomeric State within Intact Nanodiscs.

Membrane proteins play critical biochemical roles but remain challenging to study. Recently, native or nondenaturing mass spectrometry (MS) has made great strides in characterizing membrane protein interactions. However, conventional native MS relies on detergent micelles, which may disrupt natural interactions. Lipoprotein nanodiscs provide a platform to present membrane proteins for native MS within a lipid bilayer environment, but previous native MS of membrane proteins in nanodiscs has been limited by the intermediate stability of nanodiscs. It is difficult to eject membrane proteins from nanodiscs for native MS but also difficult to retain intact nanodisc complexes with membrane proteins inside. Here, we employed chemical reagents that modulate the charge acquired during electrospray ionization (ESI). By modulating ESI conditions, we could either eject the membrane protein complex with few bound lipids or capture the intact membrane protein nanodisc complex-allowing measurement of the membrane protein oligomeric state within an intact lipid bilayer environment. The dramatic differences in the stability of nanodiscs under different ESI conditions opens new applications for native MS of nanodiscs.

Correlation of Coexistent Charge Transfer States in F4TCNQ-Doped P3HT with Microstructure.

Understanding the interaction between organic semiconductors (OSCs) and dopants in thin films is critical for device optimization. The proclivity of a doped OSC to form free charges is predicated on the chemical and electronic interactions that occur between dopant and host. To date, doping has been assumed to occur via one of two mechanistic pathways: an integer charge transfer (ICT) between the OSC and dopant or hybridization of the frontier orbitals of both molecules to form a partial charge transfer complex (CPX). Using a combination of spectroscopies, we demonstrate that CPX and ICT states are present simultaneously in F4TCNQ-doped P3HT films and that the nature of the charge transfer interaction is strongly dependent on the local energetic environment. Our results suggest a multiphase model, where the local charge transfer mechanism is defined by the electronic driving force, governed by local microstructure in regioregular and regiorandom P3HT.

Unraveling the Differential Aggregation of Anionic and Nonionic Monorhamnolipids at Air-Water and Oil-Water Interfaces: A Classical Molecular Dynamics Simulation Study.

The molecular structure of a surfactant molecule is known to have a great effect on the interfacial properties. We employ molecular dynamics simulations for a detailed atomistic study of monolayers of the nonionic and anionic form of the most common congener of monorhamnolipids, α-rhamnopyranosyl-ß-hydroxydecanoyl-ß-hydroxydecanoate (( R, R)-Rha-C10-C10), at the air-water and oil-water interfaces. An atomistic-level understanding of monolayer aggregation is necessary to explain a recent experimental observation indicating that nonionic and anionic Rha-C10-C10 show surprisingly different surface area per molecule at the critical micelle concentration. Surface-pressure analysis, interface formation energy calculations, and mass density profiles of the monolayers at the air-water interface show similar properties between nonionic and anionic Rha-C10-C10 aggregation. It is found that there is a significant difference in the headgroup conformations of Rha-C10-C10 in the nonionic and anionic monolayers. Hydrogen bonding interactions between the Rha-C10-C10 molecules in the monolayers is also significantly different between nonionic and anionic forms. Representative snapshots of the simulated system at different surface concentrations show the segregation of molecular aggregates from the interface into the bulk water in the anionic Rha-C10-C10 monolayer at higher concentrations, whereas in the nonionic Rha-C10-C10 monolayer, the molecules are still located at the interface. The present work provides insight into the different aggregation properties of nonionic and anionic Rha-C10-C10 at the air-water interface. Further analyses were carried out to understand the aggregation behavior of nonionic and anionic Rha-C10-C10 at the oil-water interface. It is observed that the presence of oil molecules does not significantly influence the aggregation properties of Rha-C10-C10 as compared to those of the air-water interface.

Molecular Dynamics Simulation of the Oil Sequestration Properties of a Nonionic Rhamnolipid.

A detailed molecular dynamics simulation study is presented on the behavior of aggregates composed of the nonionic monorhamnolipid α-rhamnopyranosyl-ß-hydroxydecanoyl-ß-hydroxydecanoate (Rha-C10-C10) and decane in bulk water. A graph theoretical approach was utilized to characterize the size and composition of the many aggregates generated in our simulations. Overall, we observe that the formation of oil in Rha-C10-C10 aggregates is a favorable process. Detailed analysis on the surfactant/oil aggregate shows that larger aggregates are stable. The shape and size of the aggregates are widely distributed, with the majority of the aggregates preferring ellipsoidal or cylindrical structures. Irrespective of the decane concentration in the system, we did not observe free decane in any of the simulations. Further insights into the binding energy of decane were carried out using free-energy perturbation calculations. The results showed that the trapped decane molecules provide stability to the Rha-C10-C10 aggregates of size N = 50 which are shown to be unstable in our previous study and allow for the growth of larger aggregates than pure Rha-C10-C10 in water. The density profile plots show that decane molecules encapsulated inside the aggregate preferred to remain closer to the center of mass. This study points to the feasibility of using this biosurfactant as an environmental remediation agent.

Evolution of Aggregate Structure in Solutions of Anionic Monorhamnolipids: Experimental and Computational Results.

The evolution of solution aggregates of the anionic form of the native monorhamnolipid (mRL) mixture produced by Pseudomonas aeruginosa ATCC 9027 is explored at pH 8.0 using both experimental and computational approaches. Experiments utilizing surface tension measurements, dynamic light scattering, and both steady-state and time-resolved fluorescence spectroscopy reveal solution aggregation properties. All-atom molecular dynamics simulations on self-assemblies of the most abundant monorhamnolipid molecule, l-rhamnosyl-ß-hydroxydecanoyl-ß-hydroxydecanoate (Rha-C10-C10), in its anionic state explore the formation of aggregates and the role of hydrogen bonding, substantiating the experimental results. At pH 8.0, at concentrations above the critical aggregation concentration of 201 µM but below ∼7.5 mM, small premicelles exist in solution; above ∼7.5 mM, micelles with hydrodynamic radii of ∼2.5 nm dominate, although two discrete populations of larger lamellar aggregates (hydrodynamic radii of ∼10 and 90 nm) are also present in solution in much smaller number densities. The critical aggregation number for the micelles is determined to be ∼26 monomers/micelle using fluorescence quenching measurements, with micelles gradually increasing in size with monorhamnolipid concentration. Molecular dynamics simulations on systems with between 10 and 100 molecules of Rha-C10-C10 indicate the presence of stable premicelles of seven monomers with the most prevalent micelle being ∼25 monomers and relatively spherical. A range of slightly larger micelles of comparable stability can also exist that become increasing elliptical with increasing monomer number. Intermolecular hydrogen bonding is shown to play a significant role in stabilization of these aggregates. In total, the computational results are in excellent agreement with the experimental results.

Effect of Solvent Quality on Laminar Slip Flow Penetration of Poly(N-isopropylacrylamide) Films with an Exploration of the Mass Transport Mechanism.

The effect of solvent quality on the slip flow penetration of polymer films was evaluated by monitoring small-molecule mass transport under varying laminar flow rates using Förster resonance energy transfer in combination with total internal reflectance fluorescence microscopy (FRET-TIRFM). For thin films of poly(N-isopropylacrylamide) (pNIPAM), solvents with solvent quality ranging from good to poor were studied. The solvents used were composed of varying mole ratios of methanol and water in order to take advantage of the unique cononsolvency phenomenon of pNIPAM such that differences in the physicochemical properties of these solvents were insignificant for fluorescence detection. FRET quenching of a donor fluorophore covalently tethered on the substrate surface at the bottom of the pNIPAM film by a solution-confined acceptor was monitored as a function of time. Quenching curves were fit to a combined Taylor-Aris-Fickian mass transport model for the acceptor, rhodamine B (RhB) or 2-nitrobenzylaclohol (2-NBA), allowing apparent diffusion coefficients to be determined and used to assess slip flow penetration into the polymer film. An increase in the apparent diffusion coefficient of tracer molecules was observed with increasing laminar flow rate for all solvents, indicating that mass transport processes in the pNIPAM film are significantly perturbed by laminar slip flow penetration. In going from poor solvents, 31 mol % MeOH/H2O and 20 mol % MeOH/H2O, to the theta solvent, 13 mol % MeOH/H2O, and finally to a good solvent, 100% methanol, the slip length increases from 25 to 37 to 70 to 128 nm, with the corresponding percentage of the film penetrated by slip flow increasing from 19 to 27 to 42 to 57%, respectively. The apparent diffusion coefficients of the two acceptors, RhB and 2-NBA, which differ substantially in size and charge, in pNIPAM films under identical conditions were found to be of the same order of magnitude, albeit with a small difference (∼10%) due to inherently different diffusive properties. Therefore, the dominant mechanism for the mass transport of small molecules in densely grafted thin pNIPAM brush films is suggested to be linear Fickian diffusion under the chosen laminar flow conditions with linear flow velocities ranging from 192 to 2952 µm/s. High-quality fits to a Taylor-Aris-Fickian diffusion model of the experimental breakthrough curves obtained with both acceptor molecules further substantiate the proper use of this model and the validity of the FRET-TIRFM method.

Rhamnolipid biosurfactant complexation of rare earth elements.

Rare earth elements (REE) are vital for modern technologies and considered critical materials. This study investigated monorhamnolipid biosurfactant interactions with REE as the basis for REE recovery technology. Conditional stability constants (log ß), measured using a resin-based ion exchange method, are reported for 16 REE and metals. These results were combined with existing data for 10 other metals to assess comparative strength and determinants of binding. The stability constants could be divided into three groups: weakly, moderately, and strongly bound. The REE were all in the strongly bound group (UO22+, Eu3+, Nd3+, Tb3+, Dy3+, La3+, Cu2+, Al3+, Pb2+, Y3+, Pr3+, and Lu3+) with log ß ranging from 9.82 to 8.20. The elements Cd2+, In3+, Zn2+, Fe3+, Hg2+, and Ca2+ were moderately bound with log ß=7.17-4.10. Finally, Sr2+, Co2+, Ni2+, UO22+, Ba2+, Mn2+, Mg2+, Rb+, and K+ were weakly bound with log ß=3.95-0.96. Two log ß values are reported for the uranyl ion due to two distinct binding regions. A mixed metals study and associated selectivity coefficients confirmed monorhamnolipids preferentially remove metals with large log ß values over those with smaller values. Preferential complexation by monorhamnolipids may constitute a green pathway for recovery of REE from alternative, non-traditional sources.

Structural Properties of Nonionic Monorhamnolipid Aggregates in Water Studied by Classical Molecular Dynamics Simulations.

Molecular dynamics simulations were carried out to investigate the structure and stabilizing factors of aggregates of the nonionic form of the most common congener of monorhamnolipids, α-rhamnopyranosyl-ß-hydroxydecanoyl-ß-hydroxydecanoate (Rha-C10-C10), in water. Aggregates of size ranging from 5 to 810 monomers were observed in the simulation forming spherical and ellipsoidal structures, a torus-like structure, and a unilamellar vesicle. The effects of the hydrophobic chain conformation and alignment in the aggregate, role of monomer···monomer and monomer···water H-bonds, and conformations of monomers in the aggregate were studied in detail. The unilamellar vesicle is highly stable due to the presence of isolated water molecules inside the core adding to the binding energy. Dissociation of a monomer from a larger micellar aggregate is relatively easy compared to that from smaller aggregates as seen from potential of mean force calculations. This analysis also shows that monomers are held more strongly in aggregates of Rha-C10-C10 than the widely used surfactant sodium dodecyl sulfate. Comparisons between the aggregation behavior of nonionic and anionic forms of Rha-C10-C10 are presented.

Synthesis and Characterization of Four Diastereomers of Monorhamnolipids.

Rhamnolipids are amphiphilic glycolipids biosynthesized by bacteria that, due to their low toxicity and biodegradability, are potential replacements for synthetic surfactants. The previously limited access to pure materials at the gram scale has hindered extensive characterization of rhamnolipid structure-performance behavior. Here, we present an efficient and versatile synthetic methodology from which four diastereomers of the most common monorhamnolipid, α-rhamnopyranosyl-ß-hydroxydecanoyl-ß-hydroxydecanoate, are prepared and subsequently characterized. Exploration of their behavior at the air-water interface is reported and analyzed in terms of the absolute configuration of the lipid tail carbinols at pH 4.0 and 8.0. All diastereomers exhibit a minimum surface tension of about 28 mN/m without a significant difference between the protonated (nonionic) or deprotonated (anionic) states. At pH 4.0 (nonionic), all diastereomers have a critical micelle concentration (CMC) in the micromolar range. At pH 8.0 (anionic), CMC values for the (R,R), (S,S), and (S,R) diastereomers are approximately an order of magnitude higher than in their nonionic states, whereas the (R,S) diastereomer exhibits a CMC about five times larger.