Apolar Phase Research Articles

Preparation of pH-Responsive Poly(aspartic acid) Nanogels in Inverse Emulsion

Poly(aspartic acid) (PASP) hydrogels were prepared by cross-linking polysuccinimide (PSI) with diaminobutane followed by the mild hydrolysis of the resultant PSI gels to PASP hydrogels. The composition dependence of the gelation time and the stiffness of bulk PASP hydrogels were determined by rheometry and compression tests, respectively. The composition of the prepared PASP nanogels was chosen based on the results on bulk PASP hydrogels. Prior to nanogel preparation stability of DMSO-in-oil (inverse) emulsions was tested as a function of the chemical quality of apolar phase, the concentration of the precursor polymer and the concentration of the surfactant. PASP nanogels in the size of a few hundred nanometers were prepared by the hydrolysis of PSI nanogels synthesized in inverse emulsion. PASP nanogels showed pH-dependent swelling and strongly negative surface charge at physiological pH values, thus they can be further developed to meet the specific criteria of different bio-related applications.

Qualitative analysis of Copaifera oleoresin using comprehensive two-dimensional gas chromatography and gas chromatography with classical and cold electron ionisation mass spectrometry

Improved separation of both sesquiterpenes and diterpenic acids in Copaifera multijuga Hayne oleoresin, is demonstrated by using comprehensive two-dimensional gas chromatography (GC×GC) coupled to accurate mass time-of-flight mass spectrometry (accTOFMS). GC×GC separation employs polar phases (including ionic liquid phases) as the first dimension (1D) column, combined with a lower polarity 2D phase. Elution temperatures (Te) of diterpenic acids (in methyl ester form, DAME) increased as the 1D McReynolds’ polarity value of the column phase decreased. Since Te of sesquiterpene hydrocarbons decreased with increased polarity, the very polar SLB-IL111 1D phase leads to excessive peak broadening in the 2D apolar phase due to increased second dimension retention (2tR). The combination of SLB-IL59 with a nonpolar column phase was selected, providing reasonable separation and low Te for sesquiterpenes and DAME, compared to other tested column sets, without excessive 2tR. Identities of DAME were aided by both soft (30eV) electron ionisation (EI) accurate mass TOFMS analysis and supersonic molecular beam ionisation (cold EI) TOFMS, both which providing less fragmentation and increased relative abundance of molecular ions. The inter-relation between EI energies, emission current, signal-to-noise and mass error for the accurate mass measurement of DAME are reported. These approaches can be used as a basis for conducting of GC×GC with soft EI accurate mass measurement of terpenes, particularly for unknown phytochemicals.

Blind prediction of distribution in the SAMPL5 challenge with QM based protomer and pK a corrections.

The computation of distribution coefficients between polar and apolar phases requires both an accurate characterization of transfer free energies between phases and proper accounting of ionization and protomerization. We present a protocol for accurately predicting partition coefficients between two immiscible phases, and then apply it to 53 drug-like molecules in the SAMPL5 blind prediction challenge. Our results combine implicit solvent QM calculations with classical MD simulations using the non-Boltzmann Bennett free energy estimator. The OLYP/DZP/SMD method yields predictions that have a small deviation from experiment (RMSD = 2.3 [Formula: see text] D units), relative to other participants in the challenge. Our free energy corrections based on QM protomer and [Formula: see text] calculations increase the correlation between predicted and experimental distribution coefficients, for all methods used. Unfortunately, these corrections are overly hydrophilic, and fail to account for additional effects such as aggregation, water dragging and the presence of polar impurities in the apolar phase. We show that, although expensive, QM-NBB free energy calculations offer an accurate and robust method that is superior to standard MM and QM techniques alone.

Optically Biaxial, Re-entrant and Frustrated Mesophases in Chiral, Non-symmetric Liquid Crystal Dimers and Binary Mixtures.

Sixteen optically active, non-symmetric dimers, in which cyanobiphenyl and salicylaldimine mesogens are interlinked by a flexible spacer, were synthesized and characterized. While the terminal chiral tail, in the form of either (R)-2-octyloxy or (S)-2-octyloxy chain attached to salicylaldimine core, was held constant, the number of methylene units in the spacer was varied from 3 to 10 affording eight pairs of (R & S) enantiomers. They were probed for their thermal properties with the aid of orthoscopy, conoscopy, differential scanning calorimetry and X-ray powder diffraction. In addition, the binary mixture study was carried out using chiral and achiral dimers with the intensions of stabilizing optically biaxial phase/s, re-entrant phases and important phase sequences. Notably, one of the chiral dimers as well as some mixtures exhibited a biaxial smectic A (SmAb ) phase appearing between a uniaxial SmA and a re-entrant uniaxial SmA phases. The mesophases such as chiral nematic (N*) and frustrated phases viz., blue phases (BPs) and twist grain boundary (TGB) phases, were also found to occur in most of the dimers and mixtures. X-ray diffraction studies revealed that the dimers possessing oxybutoxy and oxypentoxy spacers show interdigitated (SmAd ) phase where smectic periodicity is over 1.4 times the molecular length; whereas in the intercalated SmA (SmAc ) phase formed by a dimer having oxydecoxy spacer the periodicity was found to be approximately half the molecular length. The handedness of the helical structure of the N* phases formed by two enantiomers was examined with the aid of CD measurements; as expected, these enantiomers showed optical activities of equal magnitudes but with opposite signs. Overall, it appears that the chiral dimers and mixtures presented herein may serve as model systems in design and developing novel materials exhibiting the apolar SmAb phase possessing D2h symmetry and nematic-type biaxiality.

Design of low hysteresis electrowetting systems in non-aqueous media by the addition of low HLB amphiphilic compounds

This study focuses on the design of non-aqueous electrowetting systems using a high surface energy dielectric coating: parylene C. The wetting properties of oils on parylene C in the presence an immiscible non-aqueous polar phase are first examined. The contact angle of the oil drop in this design is usually high (20° or more). A solution to improve the wetting of the oil is proposed. A direct relation between the action of low HLB (highly lipophilic) surfactants on the liquid/liquid surface energy and the contact angle is demonstrated. Last but not least, low hysteresis electrowetting systems using non-aqueous polar solvents and a high surface energy dielectric are proposed by adding low HLB surfactants in the oil (apolar) phase.

Hydrophobin purification based on the theory of CO2-nanobubbles

ABSTRACTPurification is a critical step to obtain hydrophobin HFBII for use in positive applications. In this study, hydrophobin HFBII was produced by Trichoderma reesei via submerged fermentation. Using the CO2-foam fractionation method yielded a fourfold increase in protein concentration. The foamate (αL-HFBII) was dried using a nano spray-dryer under optimal temperature. The gushing activity of the dried foamate (αS-HFBII) decreased. Addition of Tween 80 to the foamate before the drying process partially prevented the deactivation of hydrophobin HFBII. The purity of the powder was enhanced based on the theory of CO2-nanobubbles in a CO2-rich environment. The collected CO2-nanobubbles were added to an apolar–polar system and the interface of these two phases was collected. After evaporation of the apolar phase, the purity of the hydrophobins assembled on the surface of the liquid was significantly improved.

Molten fatty acid based microemulsions.

We show that ternary mixtures of water (polar phase), myristic acid (MA, apolar phase) and cetyltrimethylammonium bromide (CTAB, cationic surfactant) studied above the melting point of myristic acid allow the preparation of microemulsions without adding a salt or a co-surfactant. The combination of SANS, SAXS/WAXS, DSC, and phase diagram determination allows a complete characterization of the structures and interactions between components in the molten fatty acid based microemulsions. For the different structures characterized (microemulsion, lamellar or hexagonal phases), a similar thermal behaviour is observed for all ternary MA/CTAB/water monophasic samples and for binary MA/CTAB mixtures without water: crystalline myristic acid melts at 52 °C, and a thermal transition at 70 °C is assigned to the breaking of hydrogen bounds inside the mixed myristic acid/CTAB complex (being the surfactant film in the ternary system). Water determines the film curvature, hence the structures observed at high temperature, but does not influence the thermal behaviour of the ternary system. Myristic acid is partitioned in two "species" that behave independently: pure myristic acid and myristic acid associated with CTAB to form an equimolar complex that plays the role of the surfactant film. We therefore show that myristic acid plays the role of a solvent (oil) and a co-surfactant allowing the fine tuning of the structure of oil and water mixtures. This solvosurfactant behaviour of long chain fatty acid opens the way for new formulations with a complex structure without the addition of any extra compound.

HYDROPHILIC INTERACTION CHROMATOGRAPHY (HILIC): STATE OF THE ART AND APPLICATIONS

Hydrophilic interaction liquid chromatography (HILIC) has been gaining increased attention for its effective separation of highly polar compounds, which include carbohydrates, amino acids, pharmaceutical compounds, proteins, glycoproteins, nucleosides, etc. Polar compounds are usually poorly retained on reverse-phase liquid chromatography (RP-HPLC) columns or have poor solubility in the apolar mobile phase of normal-phase high performance liquid chromatography (NP-HPLC). Since HILIC uses organic solvents such as ACN or MeOH ( > 70%), also used in RP-HPLC and polar stationary phases similar to NP-HPLC (bare silica, diol, amino, amide, saccharide, zwitterionic stationary phases, etc.), it represents a hybrid of the two separation modes. The high organic content in the MP leads to good compatibility with mass spectrometry (MS), increasing the detectivity. This review describes the fundamentals of HILIC and highlights some interesting applications.

Development of soy lecithin based novel self-assembled emulsion hydrogels

The current study reports the development and characterization of soy lecithin based novel self-assembled emulsion hydrogels. Sesame oil was used as the representative oil phase. Emulsion gels were formed when the concentration of soy lecithin was >40% w/w. Metronidazole was used as the model drug for the drug release and the antimicrobial tests. Microscopic study showed the apolar dispersed phase in an aqueous continuum phase, suggesting the formation of emulsion hydrogels. FTIR study indicated the formation of intermolecular hydrogen bonding, whereas, the XRD study indicated predominantly amorphous nature of the emulsion gels. Composition dependent mechanical and drug release properties of the emulsion gels were observed. In-depth analyses of the mechanical studies were done using Ostwald-de Waele power-law, Kohlrausch and Weichert models, whereas, the drug release profiles were modeled using Korsmeyer–Peppas and Peppas–Sahlin models. The mechanical analyses indicated viscoelastic nature of the emulsion gels. The release of the drug from the emulsion gels was diffusion mediated. The drug loaded emulsion gels showed good antimicrobial activity. The biocompatibility test using HaCaT cells (human keratinocytes) suggested biocompatibility of the emulsion gels.

Synthesis of Vegetable Fat Containing Chitosan Microparticles with Improved Physical and Delivery Properties

ABSTRACTThe present study describes the encapsulation of vegetable fats (cocoa butter and mango butter) within chitosan microparticles by double emulsion technique to prevent leaching of the internal apolar phase. Leaching studies suggested negligible leaching of the internal phase (∼12–14%) when the fats were encapsulated as compared to the control (∼40%). Fourier transform infrared spectroscopy and differential scanning calorimeter studies confirmed the successful encapsulation of fats. The release of drug (ciprofloxacin) from the microparticles was diffusion and erosion mediated and were capable to elicit antimicrobial activity against Escherichia coli. The study suggests that the developed microparticles have the potential for controlled delivery of antimicrobials.

레시틴 오가노겔을 이용한 난용성 제니스테인의 용해도 향상

오가노겔은 반고형상이며 3차원의 네트워크 구조로 이루어진 친유성 용매로 이루어져 있다. 본 연구에서는 유상과 수상에서 모두 난용성 특징을 가진 제니스테인을 포함하는 레시틴 오가노겔을 개발하였다. 이 시스템은 안정할 뿐만 아니라 경피 흡수 실험에서도 높은 흡수율을 보였다. 본 오가노겔 제형에 적합한 원료들을 선별한 결과, 수화된 레시틴, 해바라기유, dipropylene glycol (DPG), polyethylene glycol (PEG)이 이 시스템에서 주로 사용되었다. 레시틴 오가노겔의 제조에 적합한 원료의 함량은 phase ternary diagram 작성을 통하여 결정하였다. 제조된 레시틴 오가노겔을 organoleptic characteristics, stability, pH, rheology, phase transition temperatures, microscopic analysis, skin penetration 실험을 통해 평가하였다. 본 연구 결과를 통해 본 논문에서 제시하는 레시틴 오가노겔 제형은 안정한 상태에서 난용성 물질을 높은 농도로 피부에 효과적으로 전달할 수 있는 제형으로 활용될 수 있을 것이라 생각된다. Organogels are semi-solid systems that consist of an apolar solvent as the liquid phase within a three-dimensional networked structure. In this study, we developed a stable and skin penetration-enhanced Lecithin Organogel (LO) containing genistein, which is one of the poorly soluble active ingredients in both polar and apolar phase. After screening of various components (type of gelators, organic and aqueous phase), hydrogenated lecithin (HL), sunflower oil (SO), dipropylene glycol (DPG), and polyethylene glycol (PEG) were mainly used in this formulation. Phase ternary diagram was employed for optimization of the composition in the LO. The formulated LO were evaluated for its organoleptic characteristics, stability, pH, rheology, phase transition temperatures, microscopic analysis and skin penetration. The optimized stable LO system can be utilized as an effective and stable cosmetic formulation that can carry poorly soluble active ingredients at high concentration for topical dermal delivery.

English

The plan of the current work was to make an index to calculate topical efficiency of a series of nonsteroidal anti-inammatory drugs Organogel, a viscoelastic system, can be regarded as a semi-solid preparation which has an immobilized external apolar phase. The apolar phase gets powerless within spaces of the three-dimensional networked arrangement formed due to the physical interactions amongst the selfassembled structures of compounds regarded as gelators. In common, organogels are thermodynamically stable in environment and have been explore as matrices for the delivery of bioactive agents. In the current document, attempts have been made to understand the properties of organogels, various types of organogelators and some applications of the organogels in controlled delivery.

Synthesis of primary amines from the renewable compound citronellal via biphasic reductive amination

The reductive amination of the natural product citronellal with ammonia is presented as a new and atom economic way to its primary amine derivatives. The aqueous ammonia phase contains the homogeneous catalytic system [Rh(cod)Cl]2/TPPTS in a biphasic solvent system, whereas the starting material and the products remain in the apolar solvent phase. This concept supresses side reactions effectively, achieving a high yield of primary amines of up to 87%. Systematic investigations demonstrate that the cleavage of the secondary imine as an undesired by-product is necessary in achieving high selectivites, which can be controlled by the reaction conditions. Surfactants, ionic liquids or native cyclodextrins and their derivates prove to be useful phase transfer agents for optimising the interaction between the organic and the aqueous phase. The use of the ionic liquid [DecMIM]Br and the cyclodextrin derivative methyl-β-cyclodextrin provided especially fast and accurate phase separation.

Ultrasonication-Assisted Preparation and Characterization of Emulsions and Emulsion Gels for Topical Drug Delivery

The current study describes the use of ultrasonication for the preparation of biphasic emulsions and emulsion gels for topical drug delivery. Sorbitan monostearate (SMS) was used as the surfactant for stabilizing the interface of sesame oil (apolar phase) and water (polar phase). Emulsions were formed at lower concentrations of SMS, whereas emulsion gels were formed at higher concentrations of SMS. The formulations were characterized by fluorescent microscopy, X-ray diffraction, viscosity, stress relaxation, spreadability, and differential scanning calorimetry studies. Fluorescence microscopy suggested formation of oil-in-water type of formulations. There was an increase in the viscosity, bulk resistance, and firmness of the formulations as the proportions of SMS was increased. The emulsion gels were viscoelastic in nature. Thermal studies suggested higher thermodynamic stability at higher proportions of either SMS or water. Metronidazole, a model antimicrobial drug, was incorporated within the formulations. The release of the drug from the formulations was found to be diffusion mediated. The drug-loaded formulations showed sufficient antimicrobial efficiency to be used as carriers for topical antimicrobial drug delivery.

Cytotoxicity of phenothiazine derivatives associated with mitochondrial dysfunction: a structure-activity investigation.

Phenothiazine derivatives are neuroleptic drugs used in the treatment of schizophrenia and anxiety. Several side effects are described for these drugs, including hepatotoxicity, which may be related to their cytotoxic activity. Working with isolated rat liver mitochondria, we previously showed that phenothiazine derivatives induced the mitochondrial permeability transition associated with cytochrome c release. Since the mitochondrial permeabilization process plays a central role in cell death, the aim of this work was to evaluate the effects of five phenothiazine derivatives (chlorpromazine, fluphenazine, thioridazine, trifluoperazine, and triflupromazine) on the viability of hepatoma tissue culture (HTC) cells to establish the structural requirements for cytotoxicity. All phenothiazine derivatives decreased the viability of the HTC cells in a concentration-dependent manner and exhibited different cytotoxic potencies. The EC50 values ranged from 45 to 125 μM, with the piperidinic derivative thioridazine displaying the most cytotoxicity, followed by the piperazinic and aliphatic derivatives. The addition of the phenothiazine derivatives to cell suspensions resulted in significant morphological changes and plasma membrane permeabilization. Octanol/water partition studies revealed that these drugs partitioned preferentially to the apolar phase, even at low pH values (≤4.5). Also, structural and electronic properties were calculated employing density functional theory. Interestingly, the phenothiazine derivatives promoted an immediate dissipation of the mitochondrial transmembrane potential in HTC cells, and the EC50 values were closely correlated with those obtained in cell viability assays, as well as the EC50 for swelling in isolated mitochondria. These results significantly contribute to improving our understanding of the specific structural requirements of the phenothiazine derivatives to induce cell death and suggest the involvement of the mitochondrial permeability transition in phenothiazine-induced cytotoxicity in HTC cells.

Structural organization of surfactant aggregates in vacuo: a molecular dynamics and well-tempered metadynamics study.

Experimental investigations using mass spectrometry have established that surfactant molecules are able to form aggregates in the gas phase. However, there is no general consensus on the organization of these aggregates and how it depends on the aggregation number and surfactant molecular structure. In the present paper we investigate the structural organization of some surfactants in vacuo by molecular dynamics and well-tempered metadynamics simulations to widely explore the space of their possible conformations in vacuo. To study how the specific molecular features of such compounds affect their organization, we have considered as paradigmatic surfactants, the anionic single-chain sodium dodecyl sulfate (SDS), the anionic double-chain sodium bis(2-ethylhexyl) sulfosuccinate (AOT) and the zwitterionic single-chain dodecyl phosphatidyl choline (DPC) within a wide aggregation number range (from 5 to 100). We observe that for low aggregation numbers the aggregates show in vacuo the typical structure of reverse micelles, while for large aggregation numbers a variety of globular aggregates occur that are characterized by the coexistence of interlaced domains formed by the polar or ionic heads and by the alkyl chains of the surfactants. Well-tempered metadynamics simulations allows us to confirm that the structural organizations obtained after 50 ns of molecular dynamics simulations are practically the equilibrium ones. Similarities and differences of surfactant aggregates in vacuo and in apolar media are also discussed.

Tricritical points in a Vicsek model of self-propelled particles with bounded confidence.

We study the orientational ordering in systems of self-propelled particles with selective interactions. To introduce the selectivity we augment the standard Vicsek model with a bounded-confidence collision rule: a given particle only aligns to neighbors who have directions quite similar to its own. Neighbors whose directions deviate more than a fixed restriction angle α are ignored. The collective dynamics of this system is studied by agent-based simulations and kinetic mean-field theory. We demonstrate that the reduction of the restriction angle leads to a critical noise amplitude decreasing monotonically with that angle, turning into a power law with exponent 3/2 for small angles. Moreover, for small system sizes we show that upon decreasing the restriction angle, the kind of the transition to polar collective motion changes from continuous to discontinuous. Thus, an apparent tricritical point with different scaling laws is identified and calculated analytically. We investigate the shifting and vanishing of this point due to the formation of density bands as the system size is increased. Agent-based simulations in small systems with large particle velocities show excellent agreement with the kinetic theory predictions. We also find that at very small interaction angles, the polar ordered phase becomes unstable with respect to the apolar phase. We derive analytical expressions for the dependence of the threshold noise on the restriction angle. We show that the mean-field kinetic theory also permits stationary nematic states below a restriction angle of 0.681π. We calculate the critical noise, at which the disordered state bifurcates to a nematic state, and find that it is always smaller than the threshold noise for the transition from disorder to polar order. The disordered-nematic transition features two tricritical points: At low and high restriction angle, the transition is discontinuous but continuous at intermediate α. We generalize our results to systems that show fragmentation into more than two groups and obtain scaling laws for the transition lines and the corresponding tricritical points. A numerical method to evaluate the nonlinear Fredholm integral equation for the stationary distribution function is also presented. This method is shown to give excellent agreement with agent-based simulations, even in strongly ordered systems at noise values close to zero.

Encapsulation of sorbitan ester-based organogels in alginate microparticles.

Leaching of the internal apolar phase from the biopolymeric microparticles during storage is a great concern as it undoes the beneficial effects of encapsulation. In this paper, a novel formulation was prepared by encapsulating the sunflower oil-based organogels in alginate microparticles. Salicylic acid and metronidazole were used as the model drugs. The microparticles were prepared by double emulsion methodology. Physico-chemical characterization of the microparticles was done by microscopy, FTIR, XRD, and DSC studies. Oil leaching studies, biocompatibility, mucoadhesivity, in vitro drug release, and the antimicrobial efficiency of the microparticles were also performed. The microparticles were found to be spherical in shape. Gelation of the sunflower oil prevented leaching of the internal phase from the microparticles. Release of drugs from the microparticles followed Fickian kinetics and non-Fickian kinetics in gastric and intestinal environments, respectively. Microparticles showed good antimicrobial activity against both Gram-positive (Bacillus subtilis) and Gram-negative (Escherichia coli) bacteria. The results suggested that the developed formulations hold promise to carry oils without leakage of the internal phase. Encapsulation of organogels within the microparticles has improved the drug entrapment efficiency and improved characteristics for controlled delivery applications.

Charge‐selective separation and recovery of organic ions by polymeric micelles

ABSTRACTCharge‐selective separation and recovery of organic ionic dyes by polymeric micelles (PMs) are reported. Branched polyethylenimine (PEI) functionalized with 4‐cetyloxybenzaldehyde (CBA) via Schiff‐base bonds (PEI@CBA) can extract an anionic dye from cationic contaminants, and transfer it from an aqueous phase into an apolar oil phase, and thus leading to separation. While a physical micelle of PAA@PS, with polyacrylic acid (PAA) as core and polystyrene (PS) as shell, can selectively extract a cationic dye from anionic contaminants. When polar, yet nonionic groups are eliminated from the core of a PM, charge selectivity can be significantly enhanced. Although many anionic–cationic dyes can form a poorly water‐soluble complex or precipitate, separation is still feasible with a reasonably designed PM. Finally, entrapment of a guest by a PM is found easy but release may be difficult; in this case, PEI@CBA with an acid‐sheddable shell, can recover the entrapped guest. It is also found the encapsulation of a dye is usually accompanied with dye stacking, resulting in a changed UV/vis spectrum. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014, 52, 872–881

An ab initio analysis of the structure of l-tryptophan tautomers in microhydrated environments, in water and in hydrophobic solvents

The free energy of tryptophan (Trp) tautomers and conformers in different aqueous and non-aqueous environments has been calculated at the MP2/aug-cc-pVDZ//B3LYP/6-31+G(d,p) level of theory. Comparison with glycine (Gly) has been done in order to discuss the influence of the hydrophobic side chain. A detailed structural analysis has been first carried out to identify the relevant neutral (non-ionized) and zwitterionic (ionized) conformations. In water solution, explicit consideration of the first solvation shell (eight water molecules) has been found to be mandatory in order to correctly describe the system and therefore we have used a combined discrete–continuum solvation model to obtain free energies in this medium. Calculations in non-aqueous solvents have been done with the continuum model. The study shows that the hydrophobicity of the indole group of the Trp side chain does not influence much the tautomerization energy of the amino acid in water. Thus, the computed free energy of Trp tautomerization amounts −8.93kcal/mol, which is not far from the theoretical and experimental values reported for the simplest natural amino acid glycine. Conversely, the free energy of transfer from water to cyclohexane has been estimated to 9.79kcal/mol, which is much smaller than the energy reported before for glycine at a similar theoretical level (18.2kcal/mol). The analysis of the results shows that the indole group yields a straightforward transfer of the neutral tautomer from the polar to the apolar phase, which requires only 0.86kcal/mol instead of the 10kcal/mol required for the neutral tautomer of glycine. The estimated energy of transfer is consistent with available experimental data for analogous systems.