Distinct Solubilization Mechanisms of Medroxyprogesterone in Gemini Surfactant Micelles: A Comparative Study with Progesterone.

The solubilization behavior of medroxyprogesterone (MP) within gemini surfactant micelles (14-6-14,2Br-) was investigated and compared with that of progesterone to uncover distinct solubilization mechanisms. We employed 1H-NMR and 2D ROESY spectroscopy to elucidate the spatial positioning of MP within the micelle, revealing that MP integrates more deeply into the micellar core. This behavior is linked to the unique structural features of MP, particularly its 17ß-acetyl group, which promotes enhanced interactions with the hydrophobic regions of the micelle, while the 6α-methyl group interacts with the hydrophilic regions of the micelle. The 2D ROESY correlations specifically highlighted interactions between the hydrophobic chains of the surfactant and two protons of MP, H22 and H19. Complementary machine learning and electron density analyses supported these spectroscopic findings, underscoring the pivotal role of the molecular characteristics of MP in its solubilization behavior. These insights into the solubilization dynamics of MP not only advance our understanding of hydrophobic compound incorporation in gemini surfactant micelles but also indicate the potential of 14-6-14,2Br- micelles for diverse drug delivery applications.

Micelle formation of sodium taurolithocholate.

The proportion of sodium taurolithocholate (NaTLC) is extremely low in human bile salts. NaTLC forms aggregates with other lipids in the bile and functions as an emulsifying and solubilizing agent. The molecular structure of NaTLC contains hydrophilic hydroxyl and sulfonic acid groups at both ends of the steroid ring. This molecular structure is similar to bolaform amphiphilic substance having hydrophilic groups at both ends due to the characteristics of its molecular structure. This study investigated the aggregate properties of the NaTLC using surface tension measurements, light scattering, small-angle X-ray scattering (SAXS), and cryo-transmission electron microscopy (cryo-TEM). Surface tension measurement showed that the surface tension of the NaTLC solution decreased to 54 mN m-1. The concentration that showed the minimum surface tension corresponded to the critical micelle concentration (CMC: 0.6 mmol L-1, 308 K) determined by the change in light scattering intensity. On the other hand, the degree of counterion (sodium ions) binding to the micelles increased with increasing NaTLC concentration. SAXS and cryo-TEM measurements showed that the NaTLC formed large string-like micelles. The surface activity and large aggregates showed the potential for use as biosurfactants. However, because of the relatively low solubility of NaTLC in water, its use as a biosurfactant is limited to a narrow concentration range.

Preferential Removal of Alkali Metal Using Dodecanoic Acid and Sodium Dodecyl Sulfate in Foam Separation System.

The selectivity of adsorption between alkali metal ions (Li+, Na+, K+, Rb+, and Cs+) based on the ionic functional groups of the surfactants was studied using two types of surfactants, dodecanoic acid (DA) and sodium dodecyl sulfate (SDS), in the foam separation system. The results showed that Li+ was preferably removed by foam separation using DA. The removal rates of other alkali metal ions were relatively low, and there were no significant differences among other alkali metal ions (Na+, K+, Rb+, and Cs+). However, Cs+ exhibited the highest removal rate among the mixed alkali metals by foam separation using SDS. From these results, the selectivity of the alkali metal in foam separation was dependent on the type of surfactant.

Micelle Formation of Dodecanoic Acid with Alkali Metal Counterions.

Alkali series with different atomic numbers affect the physicochemical properties of aqueous solutions. The micellar properties of aqueous solutions of dodecanoate as surfactants were measured by changing the counterions (C12-Na, C12-K, C12-Rb, and C12-Cs). A plot of Krafft temperature vs. alkali metal atomic number showed a downward convex curve, with its minimum temperature (20°C) in the C12-K system. By contrast, a plot of the critical micelle concentration (CMC) vs. alkali metal atomic number exhibited an upward convex curve with the maximum CMC (25.6 mmol L-1) at C12-K. Furthermore, the minimum surface tension (γ min ) of the solution at the CMC increased with increasing atomic number (C12-Na ≈ C12-K < C12-Rb < C12-Cs). The size of the dodecanoate micelles decreased with increasing atomic number. The ionization degree of the micelles also increased with increasing atomic number of the alkali metal. Small-angle X-ray scattering (SAXS) measurements revealed that alkali dodecanoate micelles formed spherical to ellipsoidal structures. In addition, micelles from the shell region showed large electrostatic repulsion, judging from the shape of the spectrum in the higher Q -1 region. From the measurement results of the solubilization of naphthalene into the micelles, the size of the micelles corresponded to the maximum solubilization quantity of naphthalene.

Biliary excretion of essential trace elements in rats under oxidative stress caused by selenium deficiency.

The excretion of essential trace elements, namely, Se, Sr, As, Mn, Co, V, Fe, and Zn into the bile of Se-deficient (SeD) Wistar male rats was studied using the multitracer (MT) technique, and instrumental neutron activation analysis (INAA). Normal and Se-control (SeC) rat groups were used as reference groups to compare the effects of Se levels on the behaviors of the essential trace elements. The excretion (% dose) of Se, Sr, As, Mn, Co, and V increased with Se levels in the liver. The biliary excretion of Mn and As dramatically enhanced for SeC rats compared with SeD rats, while that of V accelerated a little for SeC rats. The radioactivity levels of (59)Fe and (65)Zn in the MT tracer solution were insufficient to measure their excretion into bile. The role of glutathione and bilirubin for biliary excretion of the metals was discussed in relation to Se levels in rat liver.

Micelle Formation of Monoammonium Glycyrrhizinate.

Monoammonium glycyrrhizinate is produced by the neutralization of glycyrrhizic acid from plant licorice with ammonia. In this study, the physicochemical properties of aqueous monoammonium glycyrrhizinate were investigated from the viewpoint of surface chemistry. The structure of the amphiphilic molecule is bola type, comprising two glucuronic acid moieties having two carboxylic acids groups and an aglycone part having a carboxylic acid at the opposite end of the molecule from the glucuronic acids. We found that the physicochemical properties of aqueous monoammonium glycyrrhizinate are dependent on the ionization of the carboxylic acid groups. The solubility of monoammonium glycyrrhizinate gradually increased above pH 4 in the buffer solution. The critical micelle concentration (CMC) and surface tension at the CMC (γCMC) of monoammonium glycyrrhizinate were determined by the surface tension method to be 1.5 mmol L-1 and 50 mN m-1 in pH 5 buffer and 3.7 mmol L-1 and 51 mN m-1 in pH 6 buffer, respectively. The surface tension gradually decreased with increasing concentration of monoammonium glycyrrhizinate in the pH 7 buffer, but the CMC was not defined by the curve. Light scattering measurements also did not reveal a clear CMC in the pH 7 buffer. The ionization of the carboxylic acid groups in the bola-type amphiphilic molecule with increasing pH is disadvantageous for micelle formation. Cryo-transmission electron microscopy showed that monoammonium glycyrrhizinate forms rod-like micelles in pH 5 buffer, and small angle X-ray scattering experiments confirmed that the average micellar structure was rod-like in pH 5 buffer. Thus, it was found that monoammonium glycyrrhizinate can form micelles only in weakly acidic aqueous solutions.

Foam Separation of Dyes Using Anionic, Cationic, and Amphoteric Surfactants.

Foam separation can selectively remove a target substance from a solution via adsorption of the substance with the surfactant at the surface of the bubble. A cationic dye, methylene blue, and an anionic dye, Fast Green FCF, were prepared as substances to be removed via foam separation. Anionic (sodium dodecyl sulfate, SDS), cationic (dodecyltrimethylammonium chloride, DTAC), and amphoteric (3-(dodecyldimethylammonio)propane-1-sulfonate, SB-12) surfactants were used in the foam separation process. The effectiveness of the surfactants for removing the cationic methylene blue increased as follows: DTAC < SB-12 < SDS. On the other hand, the effectiveness of the surfactants for removing the anionic Fast Green FCF was in the opposite order. The dyes were effectively adsorbed by the foams via electrostatic interactions between the oppositely charged surfactant and the dye molecules. Since amphoteric surfactants have both anionic and cationic charges in a molecule, they could effectively remove both dyes in the foam separation process. Therefore, it was found that the amphoteric surfactant was highly versatile. Analysis of the kinetics of the removal rate showed that the aqueous solutions of monomers could remove the dyes more effectively than micellar solutions in foam separation.

Removal of Zwitterionic Rhodamine B Using Foam Separation.

Foam separation promotes the removal of dissolved materials from solutions by adsorbing the molecules onto a surfactant. The zwitterion of rhodamine B was removed by using both anionic (sodium dodecyl sulfate: SDS) and cationic (dodecyltrimethylammonium chloride: DTAC) surfactants through foam separation. However, rhodamine B could not be removed from a strongly acidic DTAC solution (pH 2), because the molecular form changes from the zwitterion to cation. Moreover, the cationic dye of rhodamine 6G could not be removed from the DTAC solution. Therefore, these results demonstrate that the electrostatic interaction between a surfactant and target ion is an important factor in foam separation.

Superoxide Scavenging Activity of Gold, Silver, and Platinum Nanoparticles Capped with Sugar-based Nonionic Surfactants.

Metal nanoparticles have the ability to remove superoxide via changes in the surface electronic states at the large surface area. Gold, silver, and platinum nanoparticles were prepared in the presence of three sugar-based nonionic surfactants using NaBH4 as a reducing agent. The surfactants (glycosyloxyethyl methacrylate: xGEMA) contain sugar oligomers of various lengths (x), are biodegradable, and act as protecting groups for the nanoparticles. Three types of xGEMA were used: dodecyl and hexadecyl chains containing amphiphilic oligomers (C12-3.0GEMA and C16-3.2GEMA) and multi-dodecyl chain with multiple sugar side chains (1.8C12-4.7GEMA). We found that the type of nonionic surfactant affected the size of the nanoparticles. The average size of the gold, silver, and platinum nanoparticles ranged from 1.9 to 6.6 nm depending on the surfactant. The trend in the size of gold nanoparticles in relation to the chosen surfactants was different from that for the silver and platinum nanoparticles. Moreover, the gold nanoparticles did not show effective antioxidant activity for superoxide, whereas the silver and platinum nanoparticles removed superoxide to a certain extent. The general order for superoxide scavenging activity increased in the following order: gold < platinum < silver. In particular, the largest size of silver nanoparticles capped with C16-3.2GEMA had a similar ability for the removal of superoxide as superoxide dismutase (ca. 3999 unit/mg) on the basis of the mass concentration.

Study of thermodynamic parameters for solubilization of plant sterol and stanol in bile salt micelles.

We investigated the difference between the molecular structures of plant sterols and stanols that affect the solubilization of cholesterol in bile salt micelles (in vitro study). First, the aqueous solubility of beta-sitosterol, beta-sitostanol, and campesterol was determined by considering the specific radioactivity by using a fairly small quantity of each radiolabeled compound. The order of their aqueous solubilities was as follows: cholesterol > campesterol > beta-sitostanol > beta-sitosterol. The maximum solubility of cholesterol and the above mentioned sterol/stanol in sodium taurodeoxycholate and sodium taurocholate solutions (single solubilizate system) was measured. Moreover, the preferential solubilization of cholesterol in bile salt solutions was systematically studied by using different types of plant sterols/stanols. The solubilization results showed that the cholesterol-lowering effect was similar for sterols and stanol. Thermodynamic analysis was applied to these experimental results. The Gibbs energy change (Delta G degrees ) for the solubilization of plant sterols/stanols showed a negative value larger than that for cholesterol.

Indomethacin solubilization induced shape transition in CnE7 (n=14,16) nonionic micelles.

Shape transitions were examined with regard to the solubilization of the poorly water-soluble drug indomethacin (IMC) in the nonionic surfactants heptaethylene oxide tetradecyl (C14E7) and hexadecyl (C16E7) ethers by means of a dynamic light scattering technique. The cloud points of the pure C14E7 and C16E7 micelles ranged from 58 to 62 degrees C and from 52.1 to 55.6 degrees C, respectively, at surfactant concentrations of 1 to 10 mM. The cloud points of IMC-solubilized micelles increased by approximately 1 to 5 degrees . The sizes of the pure C14E7 micelles were 4 to 14 nm at 20 to 40 degrees C at a concentration of 2 to 20 mM. The apparent hydrodynamic radius (R happ) of pure C16E7 micelles varied with temperature and concentration. C16E7 surfactant formed small spherical micelles at 20 and 25 degrees C at concentrations below 5 mM; the size of the micelles was approximately 5 nm. On the other hand, from 30 to 40 degrees C and at a higher concentration, C16E7 formed elongated cylindrical micelles, and these elongated micelles entangled or overlapped each other. The R happ of the IMC-solubilized C14E7 micelles at 20 to 40 degrees C and of C16E7 micelles at 20 degrees C increased compared to that of pure micelles. On the other hand, the cylindrical micelles of C16E7 decreased in size and turned into spherical ones because of the hydrophobicity between the micelles caused by solubilization of IMC. This phenomenon was confirmed by transmission electron microscope (TEM) images.

Thermodynamic study on competitive solubilization of cholesterol and beta-sitosterol in bile salt micelles.

Differences in the preferential solubilization of cholesterol and competitive solubilizates (beta-sitosterol and aromatic compounds) in bile salt micelles was systematically studied by changing the molar ratio of cholesterol to competitive solubilizates. The cholesterol solubility in a mixed binary system (cholesterol and beta-sitosterol) was almost half that of the cholesterol alone system, regardless of the excess beta-sitosterol quantity added. On the other hand, the mutual solubilities of cholesterol and pyrene were not inhibited by their presence in binary mixed crystals. Finally, the cholesterol solubility was measured by changing the alkyl chain length of n-alkylbenzenes. When tetradecylbenzene was added to the bile solution, the cholesterol solubility decreased slightly and was below the original cholesterol solubility. Based on Gibbs energy change (DeltaG degrees ) for solubilization, chemicals that inhibit cholesterol solubility in their combined crystal systems showed a larger negative DeltaG degrees value than cholesterol alone.

Changes in the components of biliary and plasma lipids in selenium-deficient rats.

We constructed a chronic oxidative stress model in which Se-deficient diet was fed to male Wister rats for 8 weeks. As expected, effects of oxidative damage, including Fe accumulation and increase in peroxidized lipids, were identified in the liver owing to the lack of glutathione peroxidase. Although the oxidative stress caused Fe accumulation in the liver, the Fe concentration in bile of the SeD rat was almost the same as that in the control rats. The constant excretion of Fe into bile supported the Fe accumulation in the liver. No differences were observed in the principal components of biliary lipids, i.e., bile acids, phospholipids, and cholesterol, between the two groups; moreover, these trends were also reflected in the plasma. Due to the trapping of reactive oxygen species, only bilirubin concentrations in the bile and plasma were decreased in the SeD group, when compared with those in the control group. Measurement of bilirubin concentration may be used as a supplemental oxidative stress marker.

Antibacterial activity of long-chain fatty alcohols against Staphylococcus aureus.

The antibacterial activity against Staphylococcus aureus of long-chain fatty alcohols was investigated, with a focus on normal alcohols. The antibacterial activity varied with the length of the aliphatic carbon chain and not with the water/octanol partition coefficient. 1-Nonanol, 1-decanol and 1-undecanol had bactericidal activity and membrane-damaging activity. 1-Dodecanol and 1-tridecanol had the highest antibacterial activity among the long-chain fatty alcohols tested, but had no membrane-damaging activity. Consequently, it appears that not only the antibacterial activity but also the mode of action of long-chain fatty alcohols might be determined by the length of the aliphatic carbon chain.

Study on Micelle Formation of Bile Salt Using Nuclear Magnetic Resonance Spectroscopy.

1H-nuclear magnetic resonance (1H-NMR) measurements can identify the specific protons that contribute to interactions between molecules. Using this technique, micelles formed by four bile salts: sodium taurocholate (NaTC), taurodeoxycholate (NaTDC), taurochenodeoxycholate (NaTCDC), and tauroursodeoxycholate (NaTUDC) were measured and compared in viewpoint of molecular interactions. Rotating-frame nuclear Overhauser effect and exchange spectroscopy (ROESY) analysis of the four bile salts showed differences with respect to the type of micelle formation. For all four bile salts, the key protons contributing to hydrophobic interactions were found to be the methyl protons at positions 18 and 19. The cross-peak patterns for the four bile salt species indicated pairs of characteristic proton depending on a bile salt species. The spin-lattice relaxation time (T1) of the alkyl side-chain in NaTC was relatively long compared to that of the three other bile salts, even when the concentration was higher than the critical micelle concentration (cmc). This unique behavior indicates that the hydrophilic region of NaTC molecules is flexible within their micelles. Moreover, T1 values for the typically hydrophobic methyl protons at sites C18 and C19 of NaTC were almost constant above the cmc. These results may suggest that NaTC micelles remain as small primary structures in solution unlike the three other bile salt molecules investigated in the study.

Unusual transannular cyclization products of sarcophytoxide, a 14-membered marine cembranoid: anomalous stereochemistry of epoxide-ketone rearrangement.

[reaction: see text] Treatment of sarcophytoxide with trimethylsilyl trifluoromethanesulfonate afforded an aromatic ketone as an unusual cyclization product. The modified Mosher's method and X-ray analysis performed on the aromatic ketone revealed that it is a 4:1 mixture of 8(R)- and 8(S)-enantiomers. It also suggested that the precursor ketone has 8(R)-configuration, which is contradictory to that expected from the ordinary epoxide-ketone rearrangement.

Micellization of conjugated chenodeoxy- and ursodeoxycholates and solubilization of cholesterol into their micelles: comparison with other four conjugated bile salts species.

Micelle formations of sodium glyco- and taurochenodeoxycholate (NaGCDC and NaTCDC) and sodium glyco- and tauroursodeoxycholates (NaGUDC and NaTUDC) was studied at 308.2 K for their critical micelle concentrations at various NaCl concentrations by pyrene fluorescence probe, and the degree of counterion binding to micelle was determined using the Corrin-Harkins plots. The degree of counterion binding was found to be 0.37-0.38 for chenodeoxycholate conjugates, while the determination of the degree was quite difficult for ursodeoxycholate conjugates. The change of I1/I3 values on the fluorescence spectrum with the conjugate bile salt concentration suggested two steps for their bile salt aggregation. The first step is a commencement of smaller aggregates, the first cmc, and the second one is a starting of stable aggregates, the second cmc. The aggregation number was determined at 308.2 K and 0.15 M NaCl concentration by static light scattering: 16.3 and 11.9 for sodium NaGCDC and NaTCDC, and 7.9 and 7.1 for NaGUDC and NaTUDC, respectively. The solubilization of cholesterol into the bile salt micelles in the presence of coexisting cholesterol phase and the maximum additive concentration (MAC) of cholesterol was determined against the bile salt concentration. The standard Gibbs energy change for the solubilization was evaluated, where the micelles were regarded as a chemical species. The solubilization was stabilized in the order of NaGUDC approximately = NaTUDC < NaTC < NaGC < NaTCDC < NaGCDC < NaTDC < NaGDC, where the preceding results were taken into the order.

Synthesis and Solution Properties of Adamantane Containing Quaternary Ammonium Salt-type Cationic Surfactants: Hydrocarbon-based, Fluorocarbonbased and Bola-type.

Quaternary ammonium salt-type cationic surfactants with an adamantyl group (hydrocarbon-type; CnAdAB, fluorocarbon-type; CmFC3AdAB, bola-type; Ad-s-Ad, where n, m and s represent hydrocarbon chain lengths of 8-16, fluorocarbon chain lengths of 4-8, and spacer chain length of 10-12) were synthesized via quaternization of N, N-dimethylaminoadamantane and n-alkyl bromide or 1, n-dibromoalkane. Conductivity and surface tension were measured to characterize the solution properties of the synthesized adamantyl group-containing cationic surfactants. In addition, the effects of hydrocarbon and fluorocarbon chain lengths and spacer chain length between headgroups on the measured properties were evaluated by comparison with those of conventional cationic surfactants. The critical micelle concentration (CMC) of CnAdAB and Ad-s-Ad was 2/5 of that for the corresponding conventional surfactants CnTAB and bola-type surfactants with similar number of carbons in the alkyl or alkylene chain; this was because of the increased hydrophobicity due to the adamantyl group. A linear relationship between the logarithm of CMC and the hydrocarbon chain length for CnAdAB was observed, as well as for CnTAB. The slope of the linear correlation for both surfactants was almost the same, indicating that the adamantyl group does not affect the CMC with variations in the hydrocarbon chain length. Similar to conventional surfactants CnTAB, the hydrocarbon-type CnAdAB is highly efficient in reducing the surface tension of water, despite the large occupied area per molecule resulting from the relatively bulky structure of the adamantane skeleton. On the other hand, the bola-type Ad-s-Ad resulted in increased surface tension compared to CnAdAB, indicating that the curved chain between adamantyl groups leads to poor adsorption and orientation at the air-water interface.

Micelle formation of sodium deoxycholate and sodium ursodeoxycholate (part 1).

Micellization of sodium deoxycholate (NaDC) and sodium ursodeoxycholate (NaUDC) was studied for the critical micelle concentration (CMC), the micelle aggregation number, and the degree of counterion binding to micelle, where sodium cholate (NaC) was used as a reference. The fluorescence probe technique of pyrene was employed to determine accurately the CMC values for the bile salts, which indicated that a certain concentration range of CMC and a stepwise aggregation for micellization were reasonable. The temperature dependences of micellization for NaDC and NaUDC were studied at 288.2, 298.2, 308.2, and 318.2 K by aqueous solubility change with solution pH. Aggregations of the bile salt anions were analyzed using the stepwise association model and found to grow in size with increasing concentration, which confirmed that the mass action model worked quite well. The average aggregation number was found to be 2.5 (NaUDC) and 10.5 (NaDC) at the concentration of 20 mM and at 308.2 K. The aggregation number determined by static light scattering also agreed well with those by the solubility method in the order of size: NaUDC

Solubilization of cholesterol and polycyclic aromatic compounds into sodium bile salt micelles (part 2).

The aqueous solubility of cholesterol was determined over the temperature range from 288.2 to 318.2 K with intervals of 5 K by the enzymatic method. The solubility was (3.7+/-0.3)x10(-8) mol dm(-3) (average +/- S.D.) at 308.2 K. The maximum additive concentrations of cholesterol into the aqueous micellar solutions of sodium deoxycholate (NaDC), sodium ursodeoxycholate (NaUDC), and sodium cholate (NaC) were spectrophotometrically determined at different temperatures. The cholesterol solubility increased in the order of NaUDC