Solubility In Aqueous Solutions Research Articles

Selective Neuropeptide Y Conjugates with Maximized Carborane Loading as Promising Boron Delivery Agents for Boron Neutron Capture Therapy.

G-protein-coupled receptors like the human Y1 receptor (hY1R) are promising targets in cancer therapy due to their high overexpression on cancer cells and their ability to internalize together with the bound ligand. This mechanism was exploited to shuttle boron atoms into cancer cells for the application of boron neutron capture therapy (BNCT), a noninvasive approach to eliminate cancer cells. A maximized number of carboranes was introduced to the hY1R-preferring ligand [F7,P34]-NPY by solid phase peptide synthesis. Branched conjugates loaded with up to 80 boron atoms per peptide molecule exhibited a maintained receptor activation profile, and the selective uptake into hY1R-expressing cells was demonstrated by internalization studies. In order to ensure appropriate solubility in aqueous solution, we proved the need for eight hydroxyl groups per carborane. Thus, we suggest the utilization of bis-deoxygalactosyl-carborane building blocks in solid phase peptide synthesis to produce selective boron delivery agents for BNCT.

Design, synthesis and preliminary in-vitro studies of novel boronated monocarbonyl analogues of Curcumin (BMAC) for antitumor and β-amiloyd disaggregation activity

Curcumin is currently being investigated for its capacity to treat many types of cancer and to prevent the neuron damage that is observed in Alzheimer’s disease (AD). However, its clinical use is limited by its low stability and solubility in aqueous solutions. In this study, we propose a completely new class of boronated monocarbonyl analogues of Curcumin (BMAC, 6a-c), in which a carbonyl group replaces the Curcumin β-diketone functionality, and an ortho-carborane, an icosahedral boron cluster, substitutes one of the two phenolic rings. BMAC antitumor activity against MCF7 and OVCAR-3 cell lines was assessed in vitro and compared to that of Curcumin and the corresponding MAC derivative. BMAC 6a-c showed efficiencies that are comparable to that of MAC and superior to that of Curcumin in both the cell lines. Moreover, the inhibition of the formation of β-amyloid aggregates by BMAC 6a-c was evaluated and it was shown that compound 6c, which contains two OH moieties, has a better efficiency than Curcumin. The presence of a second –OH group can enhance the compound’s binding efficacy with β-amyloid aggregates. For the future, the presence of at least one carborane group means that the BMAC antitumor effect can be coupled with Boron Neutron Capture Therapy.

Nanoadsorbents Based on NIPAM and Citric Acid: Removal Efficacy of Heavy Metal Ions in Different Media.

Heavy metal ions in aqueous solutions are harmful to human health, but exploring and exploiting nanoadsorbents with a high adsorption capacity and low cost should be an effective method for overcoming this problem. In this study, a novel nanoadsorbent termed poly(N-isopropylacrylamide-co-citric acid) (PNCA) was designed and synthesized via free-radical polymerization. PNCA exhibits good solubility in aqueous solutions and can self-assemble into spherical nanoaggregates with a mean hydrodynamic diameter of approximately 723.1 nm. After freeze-drying, the solid powder of PNCA exhibited a loose porous structure. When PNCA is dissolved in water, the resulting copolymer solution exhibits high removal rates for Cu2+ and Pb2+ of over 80%; meanwhile, over 97% of the PNCA is precipitated with metal ions. The adsorption process of PNCA chelated with Cu2+ ions fit the Freundlich model. The adsorption capacity is independent of the media pH, but could be affected by the temperature. Except for herbal medicines with alkaloids as active ingredients, PNCA also presents good adsorption capacity for Cu2+ in herbal medicine decoctions, with a removal rate of over 80%. The cell cytotoxicity in vitro and system toxicity in vivo demonstrate the desirable biosafety of PNCA. These results suggest that PNCA with good biosafety can be utilized as a nanoadsorbent to remove the metal ions, especially Cu2+, in different media.

New Family of Water-Soluble Sulfo-Fluoro Polyphosphazenes and Their Assembly within Hemocompatible Nanocoatings.

In this work, novel sulfo-fluoro polyphosphazenes (PPzs) were synthesized via macromolecular substitution of polydichlorophosphazene utilizing "non-covalent protection" methodology by converting acid functionalities into hydrophobic alkylammonium salts. Resulting PPzs showed excellent solubility in aqueous solutions over a broad pH range and contained ∼25% sulfo- groups and 20% either trifluoroethoxy- (FESP) or trifluoromethylphenoxy- (FPSP) side groups, as determined by NMR spectroscopy. Their polyelectrolyte behavior was evaluated by binding with an oppositely charged polyion, branched polyethylenimine (PEI), which resulted in the formation of interpolymer complexes as shown by dynamic light scattering (DLS). Contrary to a sulfonated, nonfluorinated PPz homopolymer (SP), fluorinated macromolecules effectively bound human serum albumin (HSA) as revealed by dynamic light scattering and asymmetric flow field flow fractionation (AF4) studies. Moreover, FESP and FPSP both displayed low hemolytic activity as evaluated in solution using porcine red blood cells. Using the layer-by-layer (LbL) technique, FESP and FPSP were assembled into nanocoatings with PEI. Both fluorinated and nonfluorinated sulfo PPzs showed linear growth with PEI because of strong ionic pairing between sulfo and amino groups. However, films of fluorinated PPzs displayed higher hydrophobicity, lower swelling, and improved stability in high ionic strength environment when compared to coatings formed by a sulfonated, nonfluorinated SP, or a carbon-chain polymer poly(styrene sulfonic acid). Hemocompatibility of FESP and FPSP nanofilms was demonstrated in vitro using whole rabbit blood hemolysis tests, which showed less than 1% hemolysis. Altogether, the present study introduces a new class of hemocompatible, sulfo-fluoropolymers that shows promise for life science applications.

Highly photostable rylene-encapsulated polymeric nanoparticles for fluorescent labeling in biological system

Rylene dyes exhibit superior photophysical properties including outstanding chemical and photochemical stabilities as well as high fluorescence quantum yields (FQYs). However, the rylene chromophores have some limitations, such as high hydrophobicity and low solubility in aqueous solution, as a fluorescent tag for biological system. Herein, we present a general method to load the rylene dyes into triblock copolymer nanoparticles (NPs) and stabilize the core. The rylene dyes in confined hydrophobic core fairly preserve their FQYs in aqueous environment. Lumogen probe nanoparticles (PNPs) were prepared with four different commercial rylenes (Lumogen Violet, Yellow, Orange and Red) in the spectral region of visible and infrared (400–750nm) and their photophysical properties were characterized. They exhibited enhanced photostability compared to commercial fluorescent dyes. Also the internalization of Lumogen PNPs in HeLa cell was confirmed by cell uptake test. These results indicate the Lumogen PNPs can be widely applicable in fluorescence detection and imaging such as flow cytometry and fluorescence microscopy.

Self-assembly of mixed systems based on nonionic and carbamate-bearing cationic surfactants as a tool for fabrication of biocompatible nanocontainers

Aggregation behavior of mixed micellar solutions and microemulsions based on cationic carbamate-bearing surfactants with hexadecyl hydrophobic group and nonionic surfactants (Tween 80, Tween 20, and Triton X 100) has been studied. Critical micelle concentrations have been determined at varying component ratios, which demonstrated a negative deviation of surfactant systems from ideal behavior (synergetic effect). The electrokinetic potential and size of aggregates have been evaluated. Solubilizing effect of individual and mixed systems toward anti-inflammatory drug meloxicam possessing pH dependent solubility in aqueous solutions has been testified by spectrophotometry. It has been determined that nonionic surfactants slightly increase the solubility of meloxicam in water, while the carbamate-bearing surfactants with the concentration of nearly 0.1% provide more than a 10-fold increase in the solubility of this drug in weakly acidic media. Carbamate-bearing surfactants are referred to a class of moderately toxic substances. Their employment in binary compositions with nonionic surfactants has decreased the toxicity of the systems with the retention of the high degree of solubilizing effect. A transition to biocompatible Tween 80/oleic acid/water/ethyl alcohol microemulsions modified with carbamate-bearing surfactant additives has increased the solubility of meloxicam by the factor of 575 as compared to water.

A Hydroxypropyl Methylcellulose-Based Solid Dispersion of Curcumin with Enhanced Bioavailability and its Hepatoprotective Activity.

Curcumin is a polyphenol compound derived from the rhizomes of Curcuma longa that exhibits antioxidant, anti-inflammatory, anticancer, and antimicrobial properties. However, its low solubility in aqueous solutions, low absorption following oral administration, and rapid degradation limit its use as a functional food material. In this study, a hydroxypropyl methylcellulose-based solid dispersion of curcumin (DW-CUR 20) was prepared and its bioavailability was evaluated. In addition, its therapeutic efficacy as a hepatoprotective agent was investigated using the model of tert-butyl hydroperoxide (t-BHP)-induced hepatocyte damage. The rat plasma pharmacokinetic study showed that the oral curcumin bioavailability of DW-CUR 20 significantly increased compared to that of non-formulated curcumin. DW-CUR 20 showed a concentration-dependent hepatocyte protective effect on t-BHP-induced HepG2 cells. DW-CUR 20 inhibited the release of lactate dehydrogenase and decreased apoptosis-related proteins such as Poly (ADP-ribose) polymerase, cleaved caspase-7 and cleaved caspase-8 on t-BHP-treated HepG2 cells. These findings suggest that DW-CUR 20 could be a promising formulation for enhancing the therapeutic efficiency of curcumin and for improving the safety.

Environmental effects of chitosan as an immobilization medium for electrochemically active small molecules

A number of challenges arise when using ferrocene as a component of electrochemical biosensors, including solubility in aqueous solutions. Therefore, entrapment of the biotin-ferrocene molecules within the chitosan film provides a route for immobilization on an electroactive surface such as an electrode while making the system water compatible. The use of the chitosan-ferrocene bioconjugate thin film on the electrode surface produces a signal that can be monitored in aqueous media. Herein, we discuss a series of modified ferrocene molecules that contain various linkers that provide non-covalent entanglement points to the chitosan medium. The electrochemical analysis and electron microscopy results show marked differences in the ferrocene loaded chitosan polymers when the termini of the ferrocene-linker vary between –SH and –NH2. The –SH modified systems showed increased reversible and robust electrochemical signals relative to the –NH2 congeners. Further studies showed that non-covalent impregnation strategy used is robust to degradation and less than 1% of the ferrocene molecules were leached over time. These results indicate that there are specific considerations needed when using chitosan-ferrocene systems as components in sensor arrays in future studies.

Emerging Nanoassembly of Polyrotaxanes Comprising Acetylated α-Cyclodextrins and High-Molecular-Weight Axle Polymer.

Acetylated α-cyclodextrin (α-CD)/poly(ethylene glycol) (PEG)-based polyrotaxanes (Ac-PRXs) with varying degrees of acetylation (DA) and molecular weight of axle PEG were synthesized and their solubility in aqueous solutions was investigated. Ac-PRXs with low DA (less than 35%) were dissolved in aqueous solutions without considering the molecular weight of axle PEG, whereas Ac-PRXs with high DA (more than 40%) and low molecular weight of axle PEG (less than 35000) were precipitated into the solutions. Interestingly, Ac-PRXs with high DA and high molecular weight of axle PEG (100000) exhibited a colloidal dispersion in aqueous solutions. It is considered that the threaded acetylated α-CDs formed hydrophobic microenvironments via hydrophobic interactions and the noncovered segments of axle PEGs provided colloidal stability. Furthermore, the potential application of Ac-PRX100k as a drug carrier was examined and it was established that Ac-PRX100k can encapsulate a hydrophobic drug. Accordingly, acetylation of PRXs is a viable approach to promote solubility in aqueous solutions and prepare self-assembled nanoparticles.

Structural Approach to Understanding the Solubility of Metal Hydroxides

We report the hierarchical structure of zirconium hydroxide after aging at different temperatures to elucidate the factors governing zirconium solubility in aqueous solutions. Zirconium hydroxide solid phases after aging at 25, 40, 60, and 90 °C under acidic to alkaline conditions were investigated using extended X-ray absorption fine structure (EXAFS), wide- and small-angle X-ray scattering (WAXS and SAXS), and transmission electron microscopy (TEM) techniques to reveal the bulk and surface structures of the solid phases from the nanoscale to sub-microscale. After aging at 25 °C, the fundamental building unit of the solid phase was considered to be tetrameric and dimeric hydroxide species. These polynuclear species formed amorphous primary particles that are approximately 3 nm in size, which in turn formed aggregates that are hundreds of nanometers in size. This hierarchical structure was found to be stable up to 60 °C under acidic and neutral conditions and up to 40 °C under alkaline conditions. After aging at 90 °C under acidic conditions and at 60 and 90 °C under alkaline conditions, the WAXS and EXAFS measurements suggested the crystallization of the solid phase. The SAXS profiles and TEM observations supported the existence of crystallized large particles about 60 nm in size, and the appearance of the Guinier region in the SAXS profiles indicated that the crystallization of the amorphous primary particles leads to the reduction of the size of the large aggregates. The transformation of the solid-phase structure by temperature was discussed in relation to the solubility product to understand the solubility-limiting solid phase. The solubility of zirconium hydroxide after aging at different temperatures was governed not only by the size of the amorphous primary particles or crystallized large particles but also by their surface configuration.

Enantioselective synthesis and biological investigation of tetrahydro-β-carboline-based HDAC6 inhibitors with improved solubility.

Aberrant epigenetic changes in DNA methylation and histone modification by acetylation or deacetylation regulate the pathogenesis of many diseases. Especially selective inhibitors are getting more and more attention. We recently reported on a new class of potent and selective anti-inflammatory and antirheumatic histone deacetylase 6 (HDAC6) inhibitors (e.g., Marbostat-100). The attachment of a morpholinoethoxy part to the head group dramatically enhances the solubility, in particular the solubility in aqueous solutions, of the lead compound Marbostat-100. Here, we present the enantioselective synthesis of small-molecule compounds based on the tetrahydro-β-carboline core system with improved solubility, and the influence of the stereochemistry on the biological activity. The enantiomers were synthesized in good enantiomeric excess (ee) purity and were potent and selective HDAC6 inhibitors, whereas the S-derivative S-21 is clearly the eutomer. The potency of our selective HDAC6 inhibitors is demonstrated by Ki values in the range of 0.5-2 nM toward HDAC6, and the selectivity was proved in cellular assays by Western blot analysis taking ac-tubulin as surrogate parameter.

Acid-Treated Water-Soluble Chitosan Suitable for Microneedle-Assisted Intracutaneous Drug Delivery.

Chitosan has been widely used as a nature-derived polymeric biomaterial due to its high biocompatibility and abundance. However, poor solubility in aqueous solutions of neutral pH and multiple fabrication steps for the molding process limit its application to microneedle technology as a drug delivery carrier. Here, we present a facile method to prepare water-soluble chitosan and its application for sustained transdermal drug delivery. The water-soluble chitosan was prepared by acid hydrolysis using trifluoroacetic acid followed by dialysis in 0.1 M NaCl solutions. We successfully fabricated bullet-shaped microneedle (MN) arrays by the single molding process with neutral aqueous chitosan solutions (pH 6.0). The chitosan MN showed sufficient mechanical properties for skin insertion and, interestingly, exhibited slow dissolving behavior in wet conditions, possibly resulting from a physical crosslinking of chitosan chains. Chitosan MN patches loading rhodamine B, a model hydrophilic drug, showed prolonged release kinetics in the course of the dissolving process for more than 72 h and they were found to be biocompatible to use. Since the water-soluble chitosan can be used for MN fabrication in the mild conditions (neutral pH and 25 °C) required for the loading of bioactive agents such as proteins and achieve a prolonged release, this biocompatible chitosan MN would be suitable for sustained transdermal drug delivery of a diverse range of drugs.

Atomistic molecular dynamics simulations of the LCST conformational transition in poly(N-vinylcaprolactam) in water

Thermoresponsive poly(N-vinylcaprolactam) (PVCL) has received growing interest due to a temperature-induced phase transition, which switches its solubility in aqueous solutions. However, the lower critical solution temperature (LCST) of PVCL is greatly influenced by the molecular weight, morphology and the environment. Therefore, despite of numerous experimental studies of the thermal response of PVCL, a driving force and a molecular origin of conformation transitions in solution remain far less studied. To get a better understanding of the coil-to-globule conformation transition of PVCL in aqueous solution, we examined the structure and conformation dynamics of a single-chain PVCL30 in a temperature range of 280–360 K by using atomistic molecular dynamics (MD) simulations. The united-atom GROMOS G53a6 force field was re-parameterized and fine-tuned by DFT calculations to reproduce the experimental LCST transition of PVCL. Our MD model reproduces the LCST transition of PVCL30 to occur within a temperature range of 34.6–38.5°. MD simulation results suggest a significant difference between the hydration state of the carbonyl group of PVCL below and above the LCST threshold. The analysis of the number of hydrogen bonds of PVCL with water molecules demonstrates that dehydration of the polymer plays an important role and drives the temperature-induced polymer collapse. Finally, the developed MD model and FF parameters were successfully tested for large-scale systems, such as mixture PVCL30 oligomer and single-chain PVCL816 polymer, respectively.

Thermo-responsive behaviors and bioactivities of hydroxybutyl chitosans prepared in alkali/urea aqueous solutions

A series of hydroxybutyl chitosans (HBCSs) with a degree of substitution (DS) ranging from 0.38 to 1.54 were homogeneously synthesized in KOH/LiOH/urea aqueous solutions under ambient conditions. The structure and solution properties of HBCSs were characterized by FT-IR, NMR, SEC-LLS, UV–vis, rheological and DLS measurements. The amino groups at C2 and hydroxyl groups at C3 and C6 participated in the reaction, although substitution mainly occurred at the hydroxyl groups at C6. The HBCSs exhibited good solubility in aqueous solutions, and those with a DS above 1.25 displayed phase separation behavior and precipitated out from solution when heated to a critical temperature. All results confirmed the hypothesis that the homogeneous KOH/LiOH/urea aqueous solution is a stable, mild, and energy-saving reaction medium for preparing HBCSs. Moreover, the HBCSs exhibited excellent biocompatibility, and even promoted the proliferation of normal cells. They also displayed antibacterial activities against Staphylococcus aureus and Escherichia coli, thus being suitable for biomedical applications.

Solubility Determination, Modeling, and Preferential Solvation of Terephthalaldehydic Acid Dissolvend in Aqueous Solvent Mixtures of Methanol, Ethanol, Isopropanol, and N-Methyl-2-pyrrolidone

The present work mainly reports the terephthalaldehydic acid solubility in aqueous solutions of methanol, ethanol, isopropanol, and NMP, which was achieved through a steady-state method covering a ...

Efficient estimation of CO2 solubility in aqueous salt solutions

Industrialization and modernization have led to an increasing trend of greenhouse gas emissions entering the atmosphere. Consequently, many countries are imposing strict environmental regulations due to increasing concern on the climate change, and a significant amount of research is being conducted to tackle this problem. Carbon capture and sequestration are one of the major methods, which can remarkably contribute to this issue since a major greenhouse gas in Earth's atmosphere is carbon dioxide (CO2). The general objective of this work was to investigate the significance of potential use of aqueous salt solutions for capturing CO2 by developing an accurate model for estimation of this phenomenon. In particular, 608 experimental data of CO2 solubility in aqueous solutions of salts as a function of temperature, pressure, salt solution concentration (molality), hydrogen bond acceptor count of salts, molecular weight of salts, and complexity value of the salts were collected from the literature. Four state-of-the-art computational methods (LSSVM, ANN, PSO-ANFIS and GA-ANFIS) were employed to examine their predictive capability for the problem. The results reveal that the LSSVM offers the highest accuracy with R2 = 0.9927 and %AARD = 5.37. Although the neural network and fuzzy interface systems are more complex approaches, the superiority of the LSSVM method for the problem under study demonstrates the easy nature of this phenomenon. Thus, the LSSVM model is recommended for estimating the CO2 solubility in aqueous salt solutions because not only it has more accuracy, but also it is easy to apply, has less mathematically complicated and less time-consuming.

Cereal proteins in nanotechnology: formulation of encapsulation and delivery systems

Cereals are an abundant and relatively inexpensive source of plant-based proteins that play critical nutritional and functional roles in foods. However, their poor solubility in aqueous solutions limits their application in many food products. A number of strategies are, therefore, being developed to overcome this limitation. Physical, chemical, and enzymatic modification of cereals protein can be used to improve their solubility and functionality. For instance, modified cereal proteins can be used as emulsifiers to stabilize lipid nanodroplets. The low water-solubility of cereal proteins is an advantage in the fabrication of protein nanoparticles created using antisolvent precipitation methods. These nanoparticles can be used to encapsulate bioactive agents or to stabilize emulsions through a Pickering mechanism.

Soluble g-C3N4 nanosheets: Facile synthesis and application in photocatalytic hydrogen evolution

The high dispersibility and solubility are highly required for the potential applications and development of well-known g-C3N4 material. In this study, a facile hydrothermal treatment and the following vacuum freezing-drying process was developed to synthesize the g-C3N4 nanosheets (ca. 5 nm) with excellent dispersibility and solubility in aqueous solutions. It was found that the melem structures with many hydrophilic groups (NH2, −OH and CO) were formed on the g-C3N4 nanosheet surface, resulting in the formation of soluble g-C3N4 (SCN) nanosheets. Moreover, the SCN nanosheets can be worked as the effective modifier to greatly increase the H2-production performance of conventional g-C3N4 photocatalyst (the resultant sample was referred to SCN/g-C3N4). Photocatalytic results revealed that the SCN/g-C3N4 sample exhibited a remarkably higher H2-production performance than the pure g-C3N4 by a factor of ca. 2. The improved H2-production rate of SCN/g-C3N4 photocatalysts could be primarily ascribed to the introduction of hydrophilic groups, which not only remarkably enhances the dispersibility and hydrophilicity of SCN/g-C3N4, but also work as the interfacial active sites to accelerate the H+-reduction reaction and the rapid formation of H2. The present soluble g-C3N4 nanosheets provide potential various applications in environmental protection and energy conversion fields.

Co-Delivery of 2-Dg and V9302 Via a Prodrug Micellar Formulation for Synergistic Targeting of Metabolism in Cancer

The unique metabolic demand of cancer cells suggests a new therapeutic strategy targeting the metabolism in cancers. V9302 is a recently reported inhibitor of ASCT2 amino acid transporter which shows promising antitumor activity by blocking glutamine uptake. However, its poor solubility in aqueous solutions and tumor cells’ compensatory metabolic shift to glucose metabolism may limit the antitumor efficacy of V9302. 2-Deoxyglucose (2-DG), a derivative of glucose, has been developed as a potential antitumor agent through inhibiting glycolysis in tumor cells. In order to achieve enhanced antitumor effect by inhibiting both metabolic pathways, a 2-DG prodrug-based micellar carrier (POEG-p-2DG) was developed. POEG-p2DG well retained the pharmacological activity of 2-DG in vitro and in vivo. More importantly, POEG-p-2DG could self-assemble to form micelles that were capable of loading V9302 to achieve co-delivery of 2-DG and V9302. V9302-loaded POEG-p2DG micelles were small in sizes (~10nm), showed a slow kinetics of drug release and demonstrated targeted delivery to tumor. In addition, V9302 loaded POEG-p-2DG micelles exhibited improved anti-tumor efficacy both in vitro and in vivo with decreased toxicity compared to free drug combination. These results suggest that POEG-p2DG prodrug micelles may serve as a dual functional carrier for V9302 to achieve synergistic targeting of metabolism in cancers.

The Influence of Pyridinium-Based Additives on Zinc Electrodeposition in Aqueous Solution

The suitability of N-ethylpyridinium bromide as a potential electrolyte additive for zinc electrodeposition in aqueous solution has been investigated by a combination of cyclic voltammetry, bulk electrolysis, scanning electron microscopy, synthesis and NMR spectroscopy. The current magnitudes of the Zn/Zn(II) redox reaction observed at the electrode decreased dramatically after a single deposition/stripping cycle in the presence of N-ethylpyridinium bromide at switching potentials more negative than −1.30 V vs Ag/AgCl. This is attributed to the reduction of the N-ethylpyridinium cation to form a pyridyl radical that subsequently and rapidly dimerizes. The proposed dimer was synthesized and shown to have a low solubility in aqueous solutions, consistent with a passivation of the electrode surface by precipitation and inhibition of redox behavior. Based on this understanding for the pyridinium cation reduction, alternative pyridinium-based additives have been examined in order to determine their influence on zinc electrodeposition.