High Solubilizing Ability Research Articles

Summarizing the Effect of Acidity and Water Content of Deep Eutectic Solvent-like Mixtures—A Review

Deep eutectic solvent-like (DES-like) mixtures re-emerged in green chemistry nineteen years ago and yet have led to a large number of publications covering different research areas and different application industries. DES-like mixtures are considered a special class of green solvents because of their unique properties, such as high solubilization ability, remarkable biocompatibility, low production cost, low volatility, relatively simple synthesis methods, and considerable stability. Several studies have been published that analyze the effect of acidity/alkalinity and water content in DES-like mixtures on their physicochemical properties and behavior. This work summarizes the characterization of green solvents and, subsequently, the influence of various factors on the resulting pH values of green solvent systems. Part of this work describes the influence of water content in DES-like mixtures on their physical and chemical properties. The acidity/alkalinity effect is very important for green solvent applications, and it has the main impact on chemical reactions. As the temperature increases, the pH of DES-like mixtures decreases linearly. The type of hydrogen bond donors has been shown to have an important effect on the acidity of DES-like mixtures. The water content also affects their properties (polarity, solubilization capacity of DES-like mixtures).

Remediation of chromium, zinc, arsenic, lead and antimony contaminated acidic mine soil based on Phanerochaete chrysosporium induced phosphate precipitation

Microbial induced phosphate precipitation (MIPP) is an advanced bioremediation technology to reduce the mobility and bioavailability of heavy metals (HMs), but the high level of HMs would inhibit the growth of phosphate solubilizing microbes. This study proposed a new combination system for the remediation of multiple HMs contaminated acidic mine soil, which included hydroxyapatite (HAP) and Phanerochaete chrysosporium (P. chrysosporium, PC) that had high phosphate solubilizing ability and HMs tolerance. Experimental data suggested that in HAP/PC treatment after 35 d of remediation, labile Cr, Zn and As could be transformed into the stable fraction with the maximum immobilization efficiencies increased by 53.01 %, 22.43 %, and 35.65 %, respectively. The secretion of organic acids by P. chrysosporium was proved to promote the dissolution of HAP. Besides, the pH value, available phosphorus (AP) and organic matter (OM) increased in treated soil than in original soil, which also indicated the related dissolution-precipitation mechanism of HMs immobilization. Additionally, characterization results revealed that adsorption and ion exchange also played an important role in the remediation process. The overall results suggested that applying P. chrysosporium coupled with HAP could be considered as an efficient strategy for the remediation of multiple HMs contaminated mine soil and laid a foundation for the future exploration of soil microenvironment response during the remediation process.

Development and Evaluation of Fast Dissolving Liquisolid Haloperidol Tablets

Aim: The aim of this study was to design fast dissolving tablets (FDT) of the anti -psychiatric drug, Haloperidol in liquisolid forms as a way to enhance its dissolution profile and anti-psychiatric effect.
 Methodology: Solubility studies of Haloperidol in various solvents and surfactants were conducted. The solvent with high solubilizing ability was tween 20 (80%), selected and absorbed into the carrier and then coating material added with other solid powder excipients, finally all powder compressed into tablets. The resulting liquisolid tablets were evaluated according to British Pharmacopoeia (B.P.) specifications. Pre- and post-compression studies were performed to determine the flow properties and evaluate the liquisolid systems, followed by in vivo studies through forced swimming test (FST).
 Results: Pre-compression studies showed adequate flowability and compatibility of liquid and solid excipients with haloperidol. The selected liquisolid tablet (LS4) demonstrated the best disintegration and water absorption ratio in addition to satisfactory friability and hardness. Attempts of in vivo dissolution results and thermodynamic stability studies showed acceptable results for the F4 formulation containing 80% Tween 20,Avicel and aerosel (0.22:81.6:10.2%), respectively. The in vivo study of (LS4) formulation revealed the highest immobility time to rats compared to control rats and others treated with purchased halonace®.
 Conclusion: Fast dissolving liquisolid tablets expressed rapid onset of action with enhanced anti-psychiatric effect of haloperidol.

Screening and identification of a Burkholderia strain and optimization of its phosphate solubilizing capacity

In order to solve the problem that soil soluble phosphorus content in most cultivated land in China is insufficient and the plant growth is inhibited, a phosphate solubilizing microorganism (PB) was screened and identified, and its phosphate solubilizing performance was optimized. The results showed that the PB strain was belonged to Burkholderia stabilis. It had the ability of nitrogen fixation and indole-3-acetic acid (IAA) secretion, as well as a certain inhibitory effect on Escherichia coli. It could maintain high activity and phosphorus solubilizing ability at pH 8.0-10.0, indicating good alkali resistance. The results of phosphorus dissolving performance optimization showed that the phosphate solubilizing capacity of strain PB reached the best at 30℃, pH 7.0, 180 r·min-1, using glucose as carbon source, ammonium sulfate as nitrogen source, tricalcium phosphate as phosphorus source and adding 50 μmol·L-1 lysine. The amount of dissolved phosphorus was 569.33 mg·L-1, which was 1.9 times of that before optimization. The strain mainly secreted citric acid, malonic acid, and glucuronic acid during metabolism. After adding lysine, the type of organic acids secreted by the strain did not change, but the content increased significantly. Results from pot experiments showed that the application of PB bacterial fertilizer could significantly improve the growth and physiological indicators of garlic seedlings, and that the promotion effect was more obvious after adding lysine. Compared with the control, the height of seedling was increased by 18.6%, seedling diameter was increased by 16.7%, aboveground fresh and dry weight were increased by 22.1% and 15.7%, and belowground fresh and dry weight were increased by 22.0% and 28.7%, respectively in PB with lysine treatment. Soil available phosphorus content was 2.1 and 2.3 times of the control in PB and PB+lysine treatments, indicating that PB could improve soil available phosphate content. Adding lysine could strengthen such function.

Isolation and identification of phosphate solubilizing bacteria from the rhizosphere of rice in organic and non-organic rice fields in Sukoharjo District, Indonesia

Abstract. Purwanti D, Setyaningsih R, Susilowati A. 2019. Isolation and identification of phosphate solubilizing bacteria from the rhizosphere of rice in organic and non-organic rice fields in Sukoharjo District, Indonesia. Bonorowo Wetlands 9: 108-115. One of the essential nutrients in the soil is phosphate. Phosphate fertilization is often inefficient because phosphate is bound and difficult for plants to absorb. The use of phosphate solubilizing bacteria (PSB) can be used as an alternative to the availability of P in the soil. This study aimed to obtain PSB isolates with high phosphate solubilization ability and identify these PSB isolates molecularly. Soil samples were taken from organic and non-organic rice (Oryza sativa L.) fields in Sukoharjo, Central Java, Indonesia, namely Grogol Village, Menuran Village, and Pondok Village. The research activity was carried out in several stages: isolation of PSB on Pikovskaya medium, characterization and testing of PSB in dissolving P, and Gram staining. PSB colonies with a phosphate solubilization index and showed different colony colors were taken, and then DNA was isolated. DNA isolation was carried out by extraction method using a DNA extraction kit. The gene encoding 16S rRNA amplified the obtained DNA samples. Sequencing was carried out using a genetic analyzer. Data analysis by comparing sequence data on the BLASTN program. Based on the isolation of rhizosphere samples from organic paddy fields, 14 isolates of PSB were obtained, and ten isolates of non-organic paddy were PSB. P13, P1, Q7, and Q8 isolates had the highest P solubilization ability with dissolution index (IP), namely 3.35, 2.13, 1.82, and 1.47. The 16S rRNA gene sequence analysis showed that isolates P1 and P13 had 99% similarity to Acinetobacter sp. ADP1 strain. The isolate Q7 had a 96% similarity with the genus Clavibacter strain NCPPB 382, ??while Q8 had a 99% similarity with Pseudomonas aeruginosa strain PAO1.

Cyclodextrin-based low melting mixtures as a solubilizing vehicle: Application to non-steroidal anti-inflammatory drugs

Poor water solubility represents a serious issue for drug formulation and delivery. Cyclodextrins (CDs) and cosolvents are valuable approaches to overcome this issue. Currently, there is a growing interest in deep eutectic solvents (DESs) with high solubilizing ability and low toxicity. Low melting mixtures (LMMs) based on CDs have recently emerged, combining the solubilizing properties of solvents and drug carriers. In this study, we evaluated the solubility of ketoprofen, flurbiprofen and naproxen in two mixtures based on levulinic acid (Lev). The effect of water on the solubilizing potential and viscosity of these mixtures was assessed. Also, the stability of the studied drugs was monitored up to one year. The LMM based on randomly methylated-β-cyclodextrin (RAMEB) showed the highest solubilizing potential (up to 5012-fold the aqueous solubility) compared to the DES based on choline chloride. Formation of RAMEB/drug inclusion complex in the LMM was evidenced by nuclear magnetic resonance spectroscopy (NMR). Adding water (10 wt%) sharply reduced the viscosity of both mixtures while maintaining their high solubilizing ability. Moreover, the studied drugs were stable up to 90% in both mixtures after a year at 25 °C. Such low-viscous mixtures endowed with high solubilizing and stabilizing properties have great potential for pharmaceutical applications.

Cyclodextrin-based Pickering nanoemulsions containing amphotericin B: Part I. evaluation of oil/cyclodextrin and amphotericin B/cyclodextrin inclusion complexes

Prior to developing cyclodextrin (CD) stabilized Pickering nanoemulsions (NEs) containing amphotericin B (AmB) for fungal keratitis therapy, the AmB solubility and the effect of CDs on complex formation of medium chain triglyceride (MCT) oils and AmB was investigated. The phase-solubility profiles of AmB in various aqueous CD solutions were determined. The AmB solubilization in oils and surfactants was also examined. Two CDs, γ-cyclodextrin (γCD) and 2-hydroxypropyl-γCD (HPγCD), along with MCT oil and lecithin were chosen because of their high solubilization ability for AmB. The solution- and solid-state characterizations of their inclusion complexes were investigated. Proton nuclear magnetic resonance studies demonstrated the formation of MCT oil/α-cyclodextrin (αCD), AmB/γCD, and AmB/HPγCD complexes. Some interactions between AmB and CDs were observed by solid-state characterizations using Fourier-transform infrared (FT-IR) spectroscopy, powder X-ray diffractometry and differential scanning calorimetry. The interfacial tension at the oil-water interface, the analysis of dissolved CD content in saturated MCT oil, and FT-IR confirmed the affinity of αCD for MCT oil. Scanning electron microscopy revealed that the MCT oil/αCD complexes can transformed into the precipitated solid complexes at high αCD concentration. Thus, the MCT oil/αCD complexes will be used as solid particles to stabilize Pickering NEs for further studies.

Application of Choline Chloride as Natural Deep Eutectic Solvents for the Green Extraction of Phenolic Compounds from Rheum Ribes Leaves

Deep eutectic solvents are applied as a new type of sustainable solvents.The new generation of green solvents are considerable utilize to extraction of bioactive compounds due to their physicochemical properties and structure. In this study, the extraction process of phenolic compounds from rhubarb roots using of ultrasound-assisted extraction (UAE) method was investigated.Totally 8 different types of choline chloride- and L-proline-based deep eutectic solvents containing various H-bond donors/acceptors were synthesized.The extraction conditions for phenolic acids such as effect of different DESs,extraction temperature,water content in nades,ratio of solid to liquid and extraction time were studied.The optimal parameters were found to be extraction time of 30 min, temperature of 313.15 K, DES 30 wt % water and solid/liquid ratio of 1:20 led to significantly effect on the extraction of phenolic contents from plant material. The quantification and characterization of two biactive flavonoids in the extracts was analyzed via ultra-high pressure liquid chromatography (UPLC) with photodiode dedection.Compared with conventional extraction system, deep eutectic solvents (DESs) showed high extraction efficiency for both polar and less polar compounds. This study reveals,the developed DESs have significant as alternative new green dissolving agents in the extraction of phenolic compounds from plant resource due to their high solubilization ability and low toxicity.

Optimization of microemulsion cleaning sludge conditions using response surface method

Microemulsion cleaning method has been proved to be an effective way to clean oily sludge with low interfacial tension and high solubilizing ability for non-miscible liquids. In this paper, the percentage range of the microemulsion in the formulation was obtained by studying phase behavior of the microemulsion. The response surface method was used to model and optimize the microemulsion to obtain the best formulation: n-BuOH content at 9.89%, NaCl content at 2.24% and AES/APG ratio at 3.75, and the oil removal rate reached 97.28%. Meanwhile, the cleaning conditions of oil sludge were also optimized by the response surface method and the optimal cleaning parameters were determined as liquid-solid ratio at 4.2, stirring rate at 157 r·min−1, and stirring time at 38 min. In addition, some experiments were carried out to confirm the simulation results, affording the oil removal rate of 98.79%. SEM and FTIR confirmed that the oil on the sludge can be removed by microemulsion.

Isolation and identification of potassium-solubilizing bacteria from Mikania micrantha rhizospheric soil and their effect on M. micrantha plants

Potassium is directly involved in plant cell turgor-driven cell elongation, this is important for promoting the expansion of invasive plants. Soil potassium-solubilizing microorganisms in some invaded ecosystems may promote plant invasion by increasing potassium availability. The aims of this study were to isolate and identify potassium-solubilizing bacteria and to evaluate their contribution to the solubilization of potassium from potassium-feldspar, and to the potassium uptake of Mikania micrantha. Potassium-solubilizing bacteria were isolated using solid Aleksandrov medium in abandoned orchards that have been highly invaded by M. micrantha for more than 10 years. Our results revealed that 18 strains of efficient bacteria were identified using liquid Aleksandrov medium. Among the isolates, the Burkholderia genus had the highest solubilizing ability (1.75 mg L−1). The results of the pot culture experiment showed that the plant biomass and potassium content of M. micrantha with potassium-solubilizing bacteria were higher than in the control without these bacteria. Incubation with potassium-solubilizing bacteria, especially GZ18, significantly increased the plant phosphorus content. More potassium was solubilized in treatments with potassium-solubilizing bacteria than in the control without bacteria. These results strongly suggest that potassium-solubilizing bacteria in the rhizosphere of M. micrantha could improve potassium solubilization and uptake, and contributed to their success as an invasive species.

Supramolecular Catalytic Systems Based on a Cationic Amphiphile and Sodium Polystyrene Sulfonate for Decomposition of Organophosphorus Pollutants

A supramolecular catalytic system for hydrolytic decomposition of toxic phosphorus acid esters has been obtained on the basis of a cationic surfactant with a morpholinium head group and sodium polystyrene sulfonate. Self-organization of the new binary catalytic system has been studied by tensiometry, conductometry, pH-metry, spectrophotometry, and dynamic and electrophoretic light scattering, and its aggregation thresholds have been determined. High solubilizing ability of the system with respect to a hydrophobic guest has been revealed. The morpholinium surfactant has been found to accelerate the hydrolysis of phosphonates up to 50 times in comparison to the reaction in water. The apparent hydrolysis rate constant in the presence of the polyelectrolyte decreases threefold due to reduction of the reactant binding constants.

New amphiphilic multiheterocycle: Micelle-forming properties and effect on the reactivity of phosphorus acid esters

Supramolecular systems based on a novel tetracationic amphiphilic multiheterocycle have been studied by tensiometry, conductometry, pH-metry, spectrophotometry, and dynamic and electrophoretic light scattering. The critical micelle concentration of the system has been determined (0.4 mM), and the possibility of open and closed association models realization has been demonstrated. A high solubilizing ability of the aggregates toward hydrophobic guest species has been revealed. Micellar catalysts based on the new multiheterocycle have shown substrate specificity in the hydrolysis of phosphonates possessing different hydrophobicities.

Evaluation of surfactant performance in in situ foam flushing for remediation of dichlorodiphenyltrichloroethane-contaminated soil

The aim of this study was to select the appropriate surfactant for the remediation of dichlorodiphenyltrichloroethane-contaminated soil using an in situ foam-flushing technique. The research investigated the performance of the nonionic surfactants polyethylene glycol octyl phenyl ether, polysorbate, and polyoxyethylene lauryl ether, as well as the anionic surfactant sodium dodecyl sulfate, in foam static characteristics, solubility enhancement of dichlorodiphenyltrichloroethane, adsorption loss onto soil, and dichlorodiphenyltrichloroethane desorption from contaminated soil using a foam-flushing approach. Considering the above four criteria, the overall performance suggested polyethylene glycol octyl phenyl ether should be selected for the remediation of dichlorodiphenyltrichloroethane-contaminated soil due to its better foamability and stability, relatively high solubilization ability for dichlorodiphenyltrichloroethane, and greatest contaminant desorption efficiency from soil via foam flushing. Results of the dichlorodiphenyltrichloroethane desorption experiments showed that desorption efficiency of dichlorodiphenyltrichloroethane by different surfactants was largely influenced by foam static characteristics and solubility enhancement of dichlorodiphenyltrichloroethane rather than adsorption loss onto soil, which indicated that foam static characteristics and solubilization ability of surfactants were two key criteria for selection of high-performance foam surfactant.

Investigation of the effect of solubility increase at the main absorption site on bioavailability of BCS class II drug (risperidone) using liquisolid technique

BCS class II drugs usually suffer inadequate bioavailability as dissolution step is the absorption rate limiting step. In this work, the effect of solubility increase at the main absorption site for these drugs was investigated using risperidone as a drug model. Liquisolid technique was applied to prepare risperidone per-oral tablets of high dissolution rate at intestinal pH (6.8) using versatile nonionic surfactants of high solubilizing ability [Transcutol HP, Labrasol and Labrasol/Labrafil (1:1) mixture] as liquid vehicles at different drug concentrations (10–30%) and fixed (R). The prepared liquisolid tablets were fully evaluated and the dissolution rate at pH 6.8 was investigated. The formulae that showed significantly different release rate were selected and subjected to mathematical modeling using DE25, MDT and similarity factor (f2). Depending on mathematical modeling results, formula of higher dissolution rate was subjected to solid state characterization using differential scanning calorimetric (DSC), infrared spectroscopy (IR) and X-ray diffraction (XRD). Finally, the drug bioavailability was studied in comparison to conventional tablets in rabbits. Results showed that liquisolid tablet prepared using Labrasol/Labrafil (1:1) mixture as liquid vehicle containing 10% risperidone is a compatible formula with law drug crystallinity and higher dissolution rate (100% in 25 min). The drug bioavailability was significantly increased in comparison to the conventional tablets (1441.711 μg h/mL and 137.518 μg/mL in comparison to 321.011 μg h/mL and 38.673 μg/mL for AUC and Cpmax, respectively). This led to the conclusion that liquisolid technique was efficiently improved drug solubility and solubility increase of BCS class II drugs at their main absorption site significantly increases their bioavailability.

Partition of n‐Butanol Among Phases and Solubilization Ability of Winsor type III Microemulsions

AbstractThe partition of n‐butanol in Winsor type III (W‐III) microemulsions was investigated in this work. Three kinds of anionic surfactants (sodium dodecyl sulfate (SDS), sodium dodecyl sulfonate (DSS), and sodium dodecyl benzene sulfonate (SDBS)) and two kinds of anionic/cationic surfactant mixtures (SDS/octadecyl trimethyl ammonium chloride (OTAC) mixtures and DSS/OTAC mixtures) were studied. Internal standard gas chromatography was employed in n‐butanol content analysis. The results showed that no water exists in the excess oil (EO) phase and no oil exists in the excess water (EW) phase. For the W‐III microemulsions obtained by salinity scanning, relatively constant n‐butanol content in the EO (11–12 v%) and EW (1–4 v%) was found under different salinities. Accurate measurement of n‐butanol content in each phase is important for those systems having low solubilization ability. For the W‐III microemulsions prepared using SDS/OTAC surfactant mixture, the percentage of n‐butanol distributed into the interfacial layer decreased while the fraction of n‐butanol in the interfacial layer first increased sharply and then tended to be stable with the addition of n‐butanol. For the different optimum W‐III microemulsion systems tested, most of the surfactant‐to‐alcohol molar ratio data are near 1:3, but obvious deviation could be observed for some data. On the basis of the accurate measurement of n‐butanol content in the EO and EW phases, the standard free energy, ΔGo→in* (T = 298.15 K) of n‐butanol transferring from the EO phase to the interfacial region was calculated. The results show negative ΔGo→in* values. For microemulsions with the same components, n‐butanol content is an important factor influencing the ΔGo→in* value, and a high absolute value of ΔGo→in* leads to high solubilization ability.

Natural Deep Eutectic Solvents as a New Extraction Media for Phenolic Metabolites in Carthamus tinctorius L.

Developing green solvents with low toxicity and cost is an important issue for the biochemical industry. Synthetic ionic liquids and deep eutectic solvents have received considerable attention due to their negligible volatility at room temperature, high solubilization ability, and tunable selectivity. However, the potential toxicity of the synthetic ionic liquids and the solid state at room temperature of most deep eutectic solvents hamper their application as extraction solvents. In this study, a wide range of recently discovered natural ionic liquids and deep eutectic solvents (NADES) composed of natural compounds were investigated for the extraction of phenolic compounds of diverse polarity. Safflower was selected as a case study because its aromatic pigments cover a wide range of polarities. Many advantageous features of NADES (such as their sustainability, biodegradability combined with acceptable pharmaceutical toxicity profiles, and their high solubilization power of both polar and nonpolar compounds) suggest their potential as green solvents for extraction. Experiments with different NADES and multivariate data analysis demonstrated that the extractability of both polar and less polar metabolites was greater with NADES than conventional solvents. The water content in NADES proved to have the biggest effect on the yield of phenolic compounds. Most major phenolic compounds were recovered from NADES with a yield between 75% and 97%. This study reveals the potential of NADES for applications involving the extraction of bioactive compounds from natural sources.

The application of soil washing for treatment of polycyclic aromatic hydrocarbons contaminated soil: A case study in a petrochemical complex

Polycyclic aromatic hydrocarbons (PAHs) are potential carcinogenic and hazardous compounds having raised appreciable environmental concerns around the world in recent decades. This research investigates the effect of soil washing on removal of PAHs in contaminated soil. The study was conducted by collecting soil samples from a petrochemical complex in south of Iran. Testing was carried out at three temperatures of 20°C, 40°C, and 80°C and washing periods of 30 min and 60 min. Moreover, two different concentrations of Triton X‐100 and Brij 35 surfactants were used throughout the experiments. The results of this research indicated that the maximum removal efficiency of PAHs was obtained using Brij 35 at concentration of 5 g/L, temperature of 80°C and washing duration of 60 min. The highest removal efficacies for anthracene, naphthalene, fluorene, and benzo(a)pyrene in coarse and fine fractions of the samples occurred at 76.24%, 86.32%, 78.54%, 85.81% and 57.50%, 63.39%, 60.87%, 79.94%, respectively. Moreover, the highest removals of total PAHs are 81.66% and 61.49%, accordingly. Furthermore, using Brij 35, benzo(a)pyrene presented maximum changes in of PAHs in the samples. It is due to the high solubilizing ability of Brij 35 for benzo(a)pyrene, its low adsorption onto soil, and also its lower CMC in comparison with the other surfactant. According to the results, the higher the surfactant concentration, washing time, and temperature are, the more removal efficiency will be. For the parameters tested, the rates of PAHs removals from the samples decreased in the order of surfactant concentration, temperature and washing duration, respectively. © 2013 American Institute of Chemical Engineers Environ Prog, 33: 107–113, 2014

Ionic liquid 1-butyl-3-methyl imidazolium tetrafluoroborate for shotgun membrane proteomics

The solubility and digestion efficiency are two crucial factors that might affect the identification of integral membrane proteins (IMPs). In this work, 1% (v/v) ionic liquid (IL), 1-butyl-3-methyl imidazolium tetrafluoroborate (BMIM BF(4)), added in NH(4)HCO(3) buffer (pH 8.3), was applied as a sample preparation buffer for IMPs analysis. Compared to the commonly used sodium dodecyl sulfate and methanol methods, the number of identified IMPs from rat brain by microcolumn reversed phase liquid chromatography (μRPLC)-electrospray ionization tandem mass spectrometry (ESI-MS/MS) was improved by over three times, which might be due to the fact that BMIM BF(4) offered high solubilizing ability for IMPs and good compatibility for tryptic digestion. Furthermore, compared to Rapigest and urea methods, with BMIM BF(4) method, the number of identified IMPs from rat brain could be improved 25% and 80%, respectively, which might be contributed to the good solubilizing ability and high thermal stability of such IL. With the sample treated by BMIM BF(4) method, by 2D-nanoSCX-RPLC-ESI-MS/MS, 1,450 non-redundant proteins and 7,978 unique peptides were identified from rat brain, and 418 proteins contained at least one predicted transmembrane domain, with false discovery rates of less than 1% for peptide identification, and at least two identified unique peptides per protein. All these results demonstrate that the BMIM BF(4) method is of high potential for the large-scale identification of IMPs.

First Chemical Synthesis, Aggregation Behavior and Cholesterol Solubilization Properties of Pythocholic Acid and 16α‐Hydroxycholic Acid

AbstractThe first chemical synthesis of pythocholic acid, a major component of python's bile, and 3α,7α,12α,16α‐tetrahydroxy‐5β‐cholan‐24‐oic acid (16α‐hydroxycholic acid), a minor component in Shoebill stork's bile, was achieved starting from readily available cholic acid in overall yields of 5 % and 5.5 %, respectively, through a common intermediate. A biomimetic template‐directed remote functionalization strategy was utilized to selectively functionalize C‐16 of the steroid skeleton. This synthesis involves a series of regio and chemoselective transformations. Pythocholic acid showed unusually low critical micellar concentration (CMC) with high cholesterol solubilization ability. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Prominent Solubilizing Effect of 2-Hydroxypropyl-β-cyclodextrin on a New Thiazolidine Derivative (FPFS-410) with Antidiabetic and Lipid-lowering Activities through Inclusion Complex Formation

2-(N-Cyanoimino)-5-{(E)-4-styrylbenzylidene}-4-oxothiazolidine (FPFS-410) is a newly synthesized thiazolidine derivative having not only antidiabetic but also lipid-lowering activities. However, this compound has an extremely low aqueous solubility (2.8×10−8 M in phosphate buffer at 25 °C). In this study, we attempted to improve the solubility of FPFS-410 in water, by means of the complexation with 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD). Further, the interaction of FPFS-410 with HP-β-CyD in 50% v/v methanol/water mixed solution was investigated by ultraviolet and 1H-nuclear magnetic resonance (NMR) spectroscopic methods, because the solubility of FPFS-410 in water was too low to study quantitatively the interaction. The results of the solubility method indicated that HP-β-CyD had a markedly high solubilizing ability to FPFS-410, e.g., the solubility of the compound was increased 200,000-fold by the addition of 40 mM HP-β-CyD. The continuous variation plot of the FPFS-410/HP-β-CyD system in 50% v/v methanol/water solution gave a maximum at a host/guest molar ratio of 1:1. 1H-NMR spectroscopic studies suggested that the stilbene moiety of FPFS-410 is preferably included in the HP-β-CyD cavity to form the 1:1 complex in 50% v/v methanol/water solution. The present results suggest that HP-β-CyD is useful for improvement of the oral bioavailability of FPFS-410.