Relationship between physicochemical properties and chemical stability of muramyldipeptide derivative B30-MDP in liposomal solutions

The muramyldipeptide derivative B30-MDP has immunoadjuvant activity and vesicle-forming ability in aqueous environments. It is therefore important to evaluate the relationship between its physicochemical properties and chemical stability for use as a vaccine adjuvant. We studied the effects of octyl--D-glucoside (O.G.) incorporation on the physicochemical properties and chemical stability in aqueous solution at pH 7.4. The changes in particle size and in the membrane fluidity of B30-MDP liposomes, which were induced by the addition of O.G., were measured to confirm the transition from micelle phase to vesicle phase. The degradation of B30-MDP in both liposomal and mixed micellar solutions was measured by reverse-phase high-performance liquid chromatography. This degradation occurred by a pseudo first-order reaction at 313, 323 and 333 K. The shelf-life of the B30-MDP solution supplemented with O.G. was approximately one-seventh of that of B30-MDP alone in the liposomal solution. The changes in thek _obs values of B30-MDP correlated well with those in membrane fluidity induced by O.G. incorporation. These results indicate that an increase in membrane fluidity labilizes B30-MDP in liposomal solution.     

Effect of cholesterol or phospholipids incorporation on vesicle formation of muramyldipeptide derivative B30-MDP

Summary The muramyldipeptide derivative B30-MDP has immunoadjuvant activity and vesicleforming ability in aqueous solutions. To assist in the clinical application of B30-MDP to liposomal vaccine, we investigated the physicochemical properties including membrane fluidity, surface charge and particle size of B30-MDP vesicles containing cholesterol, dipalmitoylphosphatidyl-choline (DPPC) or dipalmitoylphosphatidylglycerol (DPPG).The membrane fluidity of B30-MDP/cholesterol vesicles was slightly influenced by cholesterol concentration and temperature. The membrane fluidity of B30-MDP/phospholipid vesicle was dependent on temperature. ESR spectra clearly showed the good miscibility of cholesterol with B30-MDP and the occurrence of phase separation between B30-MDP and phospholipid.The surface charge and particle size of B30-MDP/cholesterol vesicles were hardly influenced by cholesterol concentration in the membrane because the membrane surface was covered with the hydrophilic region of B30-MDP. The effect of this hydrophilic region of B30-MDP on the surface charge and particle size of B30-MDP/phospholipid vesicle was greater than that of phospholipid.This study showed that the membrane structure of B30-MDP/cholesterol vesicle differed from that of B30-MDP/phospholipid vesicle. Further, the hydrophilic region of B30-MDP is considered to play an important role in the physicochemical properties and formation of the vesicle.     

Polymerization of (p‐vinylphenyl)hydrogalvinoxyl and formation of a stable polyradical derivative

4‐[(3,5‐Di‐tert‐butyl‐4‐hydroxyphenyl)(3,5‐di‐tert‐butyl‐4‐oxo‐cyclohexa‐ 2,5‐dienylidene)methyl]styrene (abbreviated as (p‐vinylphenyl)hydrogalvinoxyl) was polymerized using AIBN as an initiator to give a bright yellow polymer with M w = 3.2 × 10⁴. The polymer was oxidized to give the corresponding polyradical derivative, whose spin concentration could be increased up to about 70 mol % depending on oxidative conditions. ESR signal line‐width in the solid state was greatly increased below 200 K for the polyradical with a high spin concentration (> 50 mol %). The magnetization and magnetic susceptibility indicated weak antiferromagnetic interaction among the radical sites. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 189–198, 1999     

Effect of cholesterol or phospholipid incorporation on the chemical stability of the muramyldpeptide derivative B30-MDP in mixed vesicles

Application of the muramyldipeptide derivative B30-MDP to liposomal vaccines will aid in the development of improved high immunogenicity vaccines. To give full play to the effectiveness of B30-MDP as a liposomal vaccine, it is important to evaluate the effect of cholesterol, dimyristoylphosphatidylcholine (DMPC) or distearoylphosphatidylcholine (DSPC) incorporation on the chemical stability of B30-MDP and physicochemical properties of B30-MDP/lipid mixed vesicles from the view point of pharmaceutics.The observed degradation rate constants of B30-MDP by hydrolysis in B30-MDP/cholesterol mixed vesicles were increased with increasing concentration of cholesterol, however, those in B30-MDP/DMPC and B30-MDP/DSPC mixed vesicles were unchanged with increasing concentration of DMPC and DSPC. The degradation behavior of B30-MDP was then compared with physicochemical properties of B30-MDP/lipid mixed vesicles, such as membrane fluidity and particle size. It was apparent that the degradation of B30-MDP in B30-MDP/cholesterol mixed vesicles was influenced by the particle size, but not by the fluidity of the membranes. In the case of B30-MDP/phospholipid mixed vesicles, MDP/phospholipid mixed vesicles, the degradation of B30-MDP was not influenced by either the membranes' fluidity or the particle size of the mixed vesicles.It is considered that the degradation of B30-MDP in the mixed vesicles is dependent on the membrane state, and the addition of cholesterol to B30-MDP vesicle inhibits the mutual interaction of MDP regions, whereas the addition of phospholipids hardly influences the mutual interaction of MDP regions, possibly owing to phase separation between B30-MDP and phospholipids.     

Fluorescence response of hypocrellin B to the environmental changes in a mimic biological membrane--liposome

Liposome is well known as not only a drug-delivery system but also a simple model for biological membranes. It was reported that fluorescence properties of hypocrellins were changeable over some extreme pH values. In the current work, the effects of the microenvironments on the fluorescence properties of HB in liposome, including approximately physiological range of pH values pH = 6.0-8.0, concentration of cholesterols and ionic strength of the solution, were studied. It was found that the fluorescence intensity of HB was sensitive to and also regulated by the microenvironments. When concentration of cholesterols and ionic strength keep invariable in PBS solution, there exists the maximum for the fluorescence of HB-liposome at pH 7.4 while the minimum for that of HB at pH 7.0. In addition, when pH value keeps constant (7.2), there exists the maximum at the ionic strength of 0.12 mol/kg while that at the concentration of 6×10⁻⁴ mol/L for cholesterols. On the other hand, in PBS solution, the lower the ionic strength is, the higher the fluorescence intensity is. The environment-sensitive fluorescence may be potentially applicable to probe some specific environmental features in cells or tissues.     

Effect of a bioactive curcumin derivative on DPPC membrane: A DSC and Raman spectroscopy study

Interactions of dimethoxycurcumin (1) a lipophilic bioactive curcumin derivative with dipalmitoyl phosphatidylcholine (DPPC) were investigated. The thermodynamic changes caused by (1) and its location into DPPC lipid bilayers were monitored by differential scanning calorimetry and Raman spectroscopy. The results reveal that (1) influences the thermotropic properties of DPPC lipid membrane causing abolition of the pretransition and broadening of the phase-transition profile and slightly decreases the T_m at increasing concentrations. The Raman height intensity ratios of the peaks I_2935/2880, I_2844/2880 and I_1090/1130 are representative of the interaction of (1) with the alkyl chains and furnish information about the ratio between disorder and order that exists in the conformation of the alkyl chain. The intensity changes of the peak at 715 cm⁻¹ indicates interaction between the choline head group and (1). The Raman spectroscopy results are in agreement with the thermal analysis results. Biologically active lipophilic molecules such as (1) should be studied in terms of their interaction with lipid bilayers prior to the development of advanced lipid carrier systems such as liposomes. The results of these studies provide information on the membrane integrity and physicochemical properties that are essential for the rational design lipidic drug delivery systems.     

Fabrication of high thermal stable cured novolac/Cloisite 30B nanocomposites by chemical modification of resin structure

Cloisite 30B as a modified kind of nanoclay was utilized for the formation of 3D network based on novolac resin with high thermal stable properties. Two types of phenolic resins including neat novolac (NR) and modified novolac resin were used to create a compatible matrix with nanoclay. For this purpose, NR modified with (3‐chloropropyl)triethoxysilane (CPTES) to form SiNR. For improvement of thermal behaviors, Cloisite 30B was dispersed in matrix via ultrasonic waves and cured with hexamethylenetetramine (HMTA) to form 3D network. X‐ray diffraction (XRD) analysis was used to measure the d‐spacing in intercalated systems and results indicated the optimum amount of clay for appropriate thermal properties. Investigation of the thermal properties of the samples by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) showed that the presence of Cloisite 30B in matrix resulted in much higher thermal stability and char yield with respect to modification of novolac resin originated from formation of 3D Si–O–Si network. Also, cured modified resin and its nanocomposites showed much higher thermal stability than cured NR and its nanocomposites. Such nanocomposite materials with high thermal stability have potential applications in advanced fields such electronic, industrial molds, coatings, adhesives, and aerospace composites.     

The confirmation of the formation of clathrate-like hydrates of poly(tetrabutylammonium ethenesulfonate) and of poly(tetraisopentylammonium ethenesulfonate)

A thermal method using differential scanning calorimeter has been applied to aqueous solutions of a series of poly(tetraalkylammonium ethenesulfonates) (R₄NPES). It was found that only the salts withR=n-C₄H₉ andR=i-C₅H₁₁ could form stable hydrates having large hydration numbers. The melting point and hydration numbers of these two hydrates were 12.0°C and 30±1 for the (n-C₄H₉)₄NPES hydrate and 16.0°C and 53±2 for the (i-C₅H₁₁)₄NPES hydrate, respectively. It was concluded that these hydrates were clathrate-like essentially similar to such hydrates as (n-C₄H₉)₄NF·30H₂O and (i-C₅H₁₁)₄NF·40H₂O.     

A new tripodal rhodamine B derivative as a highly selective and sensitive fluorescence chemosensor for copper(II)

A new tripodal rhodamine B derivative 2 was designed and synthesized by tripodal trialdehyde and rhodamine B hydrazide for the first time. This derivative could be used as a fluorescent chemosensor for the selective and sensitive determination of copper(II) in Tris-HCl buffer and ethanol aqueous mixed media. Under the optimum conditions described herein, fluorescence enhancement at 557/577 nm was linearly related to the concentration of copper(II) in the range of 0.10 to 10.00×10⁻⁵ mol·L⁻¹, with a correlation coefficient of R ²=0.9964 (n=15) and a detection limit of 1.129×10⁻⁷ mol·L⁻¹ (the relative standard deviation for five repeated measurements at 4.00×10⁻⁵ mol·L⁻¹ Cu(II) was 2.2%). The absorbance measurements at 557 nm were linearly related to the concentration of Cu(II) in the range of 0.50 to 25.00×10⁻⁵ mol·L⁻¹, with a correlation coefficient of R ²=0.9948 (n=13) and a detection limit of 3.338×10⁻⁷mol·L⁻¹. Supported by the Foundation of the Governor of Guizhou Province, China (Grant No. 200617) and the Talented Person Foundation of Guizhou University (Grant No. 2007039)     

A new Cu~(2+)-induced color reaction of a rhodamine derivative N-(3-carboxy)acryloyl rhodamine B hydrazide

A new rhodamine derivative,N-(3-carboxy)acryloyl rhodamine B hydrazide(CARB),has been synthesized,and its unusual spectroscopic reaction with Cu2+ has been investigated.The derivative exhibits a rapid and reversible non-fluorescent absorption upon coordination to Cu2+,which is a rather unusual phenomenon for rhodamine B derivatives.Stoichiometric measurements using the Job's method and the molar ratio method reveal that one CARB molecule combines two Cu2+ ions,and the two Cu2+ ions play different roles:one ...     

States of water in poly(vinyl alcohol) derivative hydrogels

We studied the behavior of absorbed water in equilibrium‐swollen poly(vinyl alcohol) derivative hydrogels by differential scanning calorimetry (DSC), ¹H nuclear magnetic resonance, and wide‐angle X‐ray diffraction. By DSC, three types of water were detected, and their relative fractions were estimated. With this technique we also calculated the pore size for every sample. From the nonexponential decay of the spin–spin relaxation data, we distinguished two environmental states of the absorbed water in the samples. The relaxation times were determined. From these data, we calculated the fractions of each type of water for every hydrogel and related them to the degree of crosslinking. The X‐ray study indicated that the water absorbed in these hydrogels forms a single crystalline phase on cooling. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 1462–1467, 2003     

From a trinuclear platinum(III) phosphido derivative to a platinum(II) cluster: formation of a P-C bond

Reaction of the trinuclear Pt(III)-Pt(III)-Pt(II) [(C6F5)2Pt(III)(mu-PPh2)2Pt(III)(mu-PPh2)2Pt(C6F5)2] (2) derivative with NBu4Br or NBu4I results in the formation of the trinuclear Pt(II) complexes [NBu4][(PPh2C6F5)(C6F5)Pt(mu-PPh2)(mu-X)Pt(mu-PPh2)2Pt(C6F5)2] [X = I (3), Br (4)] through an intramolecular PPh2/C6F5 reductive coupling and the formation of the phosphine PPh2C6F5. The trinuclear Pt(II) complex [(PPh2C6F5)(C6F5)Pt(mu-PPh2)Pt(mu-PPh2)2Pt(C6F5)2] (5), which displays two Pt-Pt bonds, can be obtained either by halide abstraction in 4 or by refluxing of 2 in CH2Cl2. This latter process also implies an intramolecular PPh2/C6F5 reductive coupling. Treatment of complex 5 with several ligands (Br-, H-, and CO) results in the incorporation of the ligand to the cluster and elimination of one (X = H-) or both (X = Br-, CO) Pt-Pt bonds, forming the trinuclear complexes [NBu4][(PPh2C6F5)(C6F5)Pt(mu-PPh2)(mu-X)Pt(mu-PPh2)2Pt(C6F5)2] [X = Br (6), H (7)] or [(PPh2C6F5)(C6F5)Pt(mu-PPh2)2Pt(mu-PPh2)(CO)Pt(C6F5)2(CO)] (8). The structures of the complexes have been established on the basis of 1H, 19F, and 31P NMR data, and the X-ray structures of the complexes 2, 3, 5, and 7 have been established. The chemical relationship between the different complexes has also been studied.     

On the interlayer spacing collapse of Cloisite 30B organoclay

When used as a nanofiller for the preparation of polymer/clay nanocomposites (PCNs), Cloisite^® 30B (30B) often undergoes a d-spacing collapse, as demonstrated by a shift to wider angles of the XRD basal reflection. Such collapse has been variously attributed to organoclay contamination or, more often, to thermal degradation of the organic modifier with expulsion of the volatile products from the galleries. In this work, several PCNs loaded with 30B have been prepared by melt compounding, using different polymer matrices, and have subsequently been subjected to dissolution in appropriate solvents followed by precipitation in excess non-solvent and room temperature drying. An XRD analysis of the products has shown that this treatment makes the 30B basal plane reflection go back to the original angular position. These experiments indicate that, contrary to the situation prevailing when 30B is subjected to thermal treatments at temperatures well above the onset of degradation (∼180 °C), the d-spacing collapse observed after melt compounding 30B with polymer matrices at moderate temperatures is in fact a reversible phenomenon probably due to rearrangement of the alkyl chains of the clay modifier in a disposition intermediate between bilayer and monolayer.     

Synthesis, characterization and swelling properties of a chemically cross-linked poly(vinyl alcohol) hydrogel

A poly(vinyl alcohol) hydrogel was prepared by coupling poly(vinyl alcohol) with epichlorohydrin as the cross-linking agent. The structure of the hydrogel was characterized by FTIR and GPC techniques. Various amounts of water were added into the dry gel to swell it, and the quantity of water in various states in the partially swollen hydrogel was determined by DSC technique. The analytical results indicate that the water introduced into the dry gel first combines with the hydrophilic groups of the network chains through hydrogen bond forming non-freezable water. The weight ratio of the non-freezable water to dry gel in the hydrogels is about 0.20. After the non-freezable water is saturated, the additional water penetrates the network space and exists simultaneously both in the freezable and free water states until reaching equilibrium swelling. Translated from Acta Polymeric Sinica, 2006, (5): 671–675 (in Chinese)     

Physicochemical properties and complex formation of ethyl 2-aryl(methyl)sulfonylamino-4,5,6,7-tetrahydrobenzothiophene-3-carboxylates

Acid-base properties, solubility, and chemical stability of ethyl 2-aryl(methyl)sulfonylamino-4,5,6,7-tetrahydrobenzothiophene-3-carboxylates have been studied. Complexes of Cu(II), Co(II), and Ni(II) with one of the ligands have been prepared and isolated; their solubility products were determined.     

The use of high-speed differential scanning calorimetry (Hyper-DSC™) to study the thermal properties of carbamazepine polymorphs

The thermal properties of two polymorphs of the drug carbamazepine, Forms I and III, were studied using high-speed differential scanning calorimetry (DSC). Previously, accurate determination of the heat enthalpy of fusion of Form III has not been possible using DSC at typical heating rates, due to concurrent exothermic recrystallisation to the higher-melting Form I. Here, it is demonstrated that heating rates of 250° C/min altered the kinetics of the melting transition of Form III such that this concurrent exothermic recrystallisation was inhibited. This allowed direct measurement of the enthalpy of the melting endotherm for Form III from a single transition. The enthalpy of this transition was found to be 109.5 J/g. Further investigations were then performed to test the utility of this technique in quantifying relative amounts of Forms I and III in mixtures of the two polymorphs. It was demonstrated that a limit of detection of 1% (w/w) was possible in this system. However, accurate quantification was not possible due to seeding effects initiating recrystallisation to Form I in these mixtures, even at these elevated heating rates. The utility of this novel technique as a fast analytical tool for studying the polymorphic behaviour of metastable polymorphs has been successfully demonstrated.     

Mesophase properties of N-glycidyl(ityl)-amides

Galactose, glucose, xylose and corresponding itol derivatives with the general formula Su—ZR in which Z is an amido group either NHCO (type I) or NR'CO (type II) were synthetized and their mesophasic behaviour studied. It was shown that the thermotropic and lyotropic phase transition temperatures are influenced by the following structural parameters: alkyl or perfluoroalkyl chain length, Z junction, free OH group number, cyclic or acyclic Su structure.This revised version was published online in November 2005 with corrections to the Cover Date.     

Evaluation of host-guest complex formation between a benzimidazolic derivative and cyclodextrins by UV-VIS spectrophotometry and differential scanning calorimetry

Interactions between a benzimidazolic derivative, omeprazole (OME), beta-cyclodextrin (βCD) and a chemically modified βCD, methyl-beta-cyclodextrin (MβCD) were investigated in aqueous solution by UV-VIS spectroscopy and in solid state by differential scanning calorimetry (DSC). Phase solubility studies were used to evaluate the complexation in aqueous solution. The two solubility diagrams obtained were A_L type, indicating the formation of a drug-cyclodextrin complex with 1:1 stoichiometry. The complex of OME with MβCD showed a higher stability constant (K _S) than those with βCD. Some evidences of inclusion complexation in solid state were obtained from DSC. Only in thermal curves of OME-βCD lyophilized product and in OME-MβCD spray-dried and lyophilized systems the melting point of the drug disappeared completely suggesting the possible formation of an inclusion complex.     

Synthesis and properties of a hexadecyl derivative of bis(ethylenedithio)tetrathiafulvalene (hexadecyl BEDT-TTF)

Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 131–132, January, 1990.     

Thermal properties of rhodium(III) chloride

Thermal decomposition of rhodium(III) chloride under inert, oxidative and reductive gas atmospheres was investigated in order to determine its thermal properties. Stoichiometries of the reactions occurring during heating are described. it is suggested that the chemical formula of soluble rhodium(III) chloride should be presented as RhCl₃·HCL·xH₂O. Cold crystallisation of anhydrous rhodium(III) chloride at a temperature of about 500°C was established. The procedure for quantitative determination of volatile matter (water and hydrochloric acid) content and rhodium content by thermogravimetry is given and discussed. The repeatability and reproducibility of the method are estimated. This revised version was published online in July 2006 with corrections to the Cover Date.