Local Environment of Sc and Y Dopant Ions in Aluminum Nitride Thin Films.

The local environments of Sc and Y in predominantly ⟨002⟩ textured, Al1-xDoxN (Do = Sc, x = 0.25, 0.30 or Y, x = 0.25) sputtered thin films with wurtzite symmetry were investigated using X-ray absorption (XAS) and photoelectron (XPS) spectroscopies. We present evidence from the X-ray absorption fine structure (XAFS) spectra that, when x = 0.25, both Sc3+ and Y3+ ions are able to substitute for Al3+, thereby acquiring four tetrahedrally coordinated nitrogen ligands, i.e., coordination number (CN) of 4. On this basis, the crystal radius of the dopant species in the wurtzite lattice, not available heretofore, could be calculated. By modeling the scandium local environment, extended XAFS (EXAFS) analysis suggests that when x increases from 0.25 to 0.30, CN for a fraction of the Sc ions increases from 4 to 6, signaling octahedral coordination. This change occurs at a dopant concentration significantly lower than the reported maximum concentration of Sc (42 mol % Sc) in wurtzite (Al, Sc)N. XPS spectra provide support for our observation that the local environment of Sc in (Al, Sc)N may include more than one type of coordination.

Anomalous viscosity-time behavior of polysaccharide dispersions.

Using viscosity and dynamic light scattering (DLS) measurements, we monitored the changes in the properties of dispersions of chitosan (a cationic polysaccharide) in acidic solution over a period of up to 700 h. Different polymer concentrations, weight average molecular weights, and degrees of deacetylation were examined. We found that the solution rheology and chitosan aggregates continue to change even up to 700 h. It was observed, remarkably, using both capillary and cone and plate viscometry that the viscosity decreased significantly during the storage period of the chitosan dispersions, with a rapid initial decrease and a slow approach to the steady state value. DLS measurements over this period could be interpreted in terms of a gradual decrease in the size of the chitosan aggregates in the dispersion. This behavior is puzzling, insofar as one expects the dissolution of compact polymer aggregates with time into individual polymer chains to increase the viscosity rather than decrease it as observed: We attribute this apparently anomalous behavior to the fact that the chitosan aggregates are rigid crystalline rod-like entities, which dissolved with time from dispersion of overlapping rods (with high viscosity) into solution of individual random coils (with lower viscosity). A detailed model comparing the hydrodynamic behavior of the initial overlapping rod-like aggregates with the subsequent free coils in solution is in semi-quantitative agreement with our observation.

Water-dilutable microemulsions for transepithelial ocular delivery of riboflavin phosphate.

Riboflavin phosphate (RFP) is an essential compound in the treatment of keratoconus - a degenerative, non-inflammatory disease of the cornea. Currently, the quantitative and efficient transport of riboflavin to the cornea is possible after mechanical removal of the epithelium. To avoid surgical intervention, it is therefore important to develop a method for quantitatively transporting riboflavin across the intact epithelium. In the present study, an RFP-loaded microemulsion was prepared, which could potentially function as an ocular drug delivery system crossing the eye epithelium. The specially designed water-dilutable microemulsion was based on a mixture of nonionic surfactants. Propylene glycol and glycerol acted as cosurfactant and cosolvent assisting in the solubilization of the RFP. The glycerol-rich water-free concentrate consisted of direct micelles for which glycerol served as the hydrophilic phase. In formulations with up to 40wt% water, the hydrophilic surfactant headgroups and glycerol strongly bind water molecules (DSC and SD-NMR). Above 60wt% water, globular, O/W nanodroplets, ∼14nm in diameter, are formed (SAXS, cryo-TEM, and SD-NMR). The structure of microemulsions loaded with 0.14-4.25wt% RFP (0.29-8.89mmol per 100g formulation) is not significantly influenced by the presence of the RFP. However, in the microemulsions containing 10-80wt% water, the mobility of RFP in the microemulsion is constrained by strong interactions with the surfactants and cosurfactant, and therefore free transport of the molecule can be achieved only upon higher (>80wt%) water dilutions.

Propofol solubilization and structural transformations in dilutable microemulsion.

Propofol (2,6-diisopropylphenol) is a drug for both induction and maintenance of anesthesia. Pure propofol cannot be injected because of its lipophilic character, low water-solubility, and low bioavailability. Presently, propofol is formulated in an unstable emulsion, easily oxidized, and easily contaminated with bacteria. We are proposing new, propofol-loaded modified microemulsions, stable thermodynamically, and microbiologically safe; the microemulsions are fully dilutable with water. Structural characterization of the empty and the propofol-loaded systems as a function of water dilution was accomplished using advanced analytical tools such as SD-NMR, SAXS, cryo-TEM, DSC, electrical conductivity, and viscosity. Upon water dilution the propofol-loaded concentrate forms swollen reverse micelles that upon further dilution (40 wt% water) progressively transform into a bicontinuous mesophase and then invert (>65 wt% water) into O/W nanodroplets without "losing" the solubilized propofol. The drug exhibits strong interactions with the surfactant (DSC and SD-NMR). Propofol increases the size of the microemulsion nanodroplets, but does not modify the microemulsion behavior. Water, ethanol, and PG are essential structural components, but do not interact directly with propofol.

Solubilization of simvastatin and phytosterols in a dilutable microemulsion system.

The usual treatment of hypercholesterolemia includes a class of drugs known as statins (simvastatin among them), which inhibit the production of cholesterol. Another way of reducing cholesterol levels is with the use of phytosterols, which reduce the transport of exogenic cholesterol from the intestine into the blood stream. The two treatments can be combined, achieving an additive effect. However, both simvastatin and phytosterols are practically insoluble in water, and therefore their absorption and activity are low. Nanosized self-assembled structured liquid systems are modified microemulsions that present an alternative pathway for improving the bioavailability of poorly water-soluble drugs. The goal of this study was to solubilize the maximal quantity of both simvastatin and phytosterols in a single, fully dilutable microemulsion system. We constructed a water-dilutable liquid drug delivery system that includes sucrose monolaurate, propylene glycol, and oleyl lactate. This system exhibits high solubilization capacity for both simvastatin (7.0 wt%) and phytosterols (3.5 wt%) when each is solubilized separately in a water-free concentrate. When simvastatin and phytosterols were solubilized together at a wt ratio of 2.5:1, maximum solubilization was obtained with 4.7 wt% simvastatin and 1.9 wt% phytosterols. Structural and analytical methods were applied including rheology, DSC, SD-NMR, SAXS, and cryo-TEM. The water-free "concentrate" consisted of direct micelles for which propylene glycol served as the hydrophilic phase. Upon water dilution, the direct micelles appear to form "lipophilic compounds dispersed in hydrophilic continuous phase". The solubilizates are located in the droplet core and/or at the interface.

Mesomorphic properties of the neat enantiomers of a chiral pyramidic liquid crystal.

The crown form of nona-octanoyloxy tribenzocyclononatriene (C8) with C(3) symmetry was prepared and separated into its enantiomers (C8A and C8B) by HPLC. Like the racemate, the neat enantiomers are also mesogenic, exhibiting two mesophases, M and Col(h). Differential scanning calorimetry, X-ray diffraction, carbon-13 NMR and UV circular dichroism are used to study the structural and dynamic properties of these chiral mesophases. The high-temperature mesophase (Col(h)) was identified by X-ray diffraction as columnar hexagonal; this phase is thermally unstable, undergoing racemization on heating before its clearing point is reached. The low-temperature mesophase (M) is most likely also columnar, but its symmetry could not be determined. In comparison with the racemate, the chiral mesophases are less well ordered, more tightly packed and they have a lower tendency to crystallize. On the other hand they are considerably more mobile, as reflected in their NMR spectra. No helical structure has been identified in the X-ray diffraction of the mesophases.

Structural and optical isomers of nonamethoxy cyclotriveratrylene: separation and physical characterization.

The paper concerns the structural and optical isomers of nonamethoxy-tribenzocyclononene (compound 1). In the first part of the paper it is shown that 1 exists in two structural isomers: a rigid crown (c-1) with C3 symmetry and a flexible saddle (s-1) with C1 symmetry. The latter, not previously known, can be prepared from the as-synthesized c-1 by quenching a hot solution (or the melt) followed by HPLC separation. The crown/saddle equilibrium, isomerization kinetics, and associated thermodynamic parameters in various organic solvents are reported. Carbon-13 MAS NMR, X-ray diffraction, and differential scanning calorimetry (DSC) of polycrystalline c-1 and s-1 racemates are also reported. The different melting points of the isomers and their rapid isomerization in the melt result in unconventional DSC thermograms involving multiple endothermic and exothermic transitions. The second part of the paper concerns the chiral properties of 1. Both the saddle and crown isomers are structurally chiral, but due to the fast pseudorotation of s-1 in solution, it cannot be separated into its enantiomers. Those of c-1 were separated by HPLC using a chiral column. Their X-ray structure and melting points differ considerably from those of the racemate. This and their fast racemization in the melt lead to complex DSC thermograms with multiple transitions. Solutions of the neat enantiomers exhibit a relatively small specific optical rotation. In the UV they show circular dichroism for the B1u and B2u transitions, with the latter exhibiting a clear couplet structure. Infrared and vibrational circular dichroism spectra of the enantiomers in solution are reported. Comparison of these spectra with quantum mechanical simulations provides unambiguous identification of the enantiomers.

Competitive solubilization of cholesterol and phytosterols in nonionic microemulsions.

It is well documented that phytosterols inhibit the uptake of exogenic cholesterol and do not interfere with cholesterol synthesis or cause side effects. The mechanism by which phytosterols interfere with cholesterol absorption is not completely clear and there are at least three hypotheses for their beneficial activity. Among these is that of competitive solubilization of phytosterols and cholesterol in dietary mixed micelles. In the present study we investigated the competitive solubilization of phytosterols (approximately 50% beta-sitosterol) and cholesterol in a nonionic microemulsion system constructed as a model for the dietary mixed micelles. We studied the effect of the competitive solubilization of cholesterol and phytosterols on the structural transformations and physical properties of the microemulsion and evaluated the locus of the solubilizates within the nanodroplets of each sterol separately and when they are loaded together at different weight ratios along one dilution line. Our results show that chemical and structural differences between cholesterol and phytosterols significantly influence the solubilization capacity of the nonionic microemulsion. Cholesterol, being more amphiphilic, is solubilized more efficiently at the W/O microemulsion interface, while in the O/W microemulsion phytosterols are dissolved somewhat more efficiently in the droplet core.

Titanium phosphonate porous materials constructed from dendritic tetraphosphonates.

An organic-inorganic hybrid material, TPPhA-Ti, was constructed by non-hydrolytic condensation of a dendritic tetrakis-1,3,5,7-(4-phosphonatophenyl)adamantane precursor and titanium(IV) isopropoxide. One preparative pathway yielded insoluble materials with a Ti/P ratio of approximately 1 which was confirmed by a combination of FT-IR, TGA, and EDS measurements. N2 sorption experiments showed that TPPhA-Ti is a porous solid (micropores approximately 13 A; mesopores approximately 38 A) with a high surface area, approximately 550 m2 g(-1). The structure and morphology of the TPPhA-Ti as investigated by transmission and scanning electron microscopy showed a layered-type material. Additional X-ray diffraction data suggest a paracrystalline material; an optimization of possible molecular arrangements of TPPhA-Ti was simulated that was in agreement with the experimental data. A second preparative pathway yielded a Ti oxide-phosphonate with a Ti/P ratio of approximately 3.4. Both TEM and SEM revealed that hollow nanospheres were formed with diameters of approximately 180-300 nm.

Mesomorphism, isomerization, and dynamics in a new series of pyramidic liquid crystals.

Nona-alkanoyloxy tribenzocyclononene (CTV-n, where n is the number of carbons in the side chains) were prepared for n = 2 to 14. The homologues of this series appear in two stable isomeric forms, rigid crown and flexible saddle. We report on their isomerization equilibria and dynamics in solution and on their mesomorphic properties in the neat state. The crown-saddle equilibrium and interconversion kinetics of the CTV-8 isomers were studied in dimethyl formamide solutions using high-resolution (1)H NMR in the temperature range from 50 to 130 degrees C. At lower temperatures, the isomerization is too slow to measure. In this range the equilibrium saddle fraction increases from approximately 0.40 to approximately 0.65, whereas the isomerization rate increases from approximately 10(-)(4) to approximately 1 s(-)(1). The saddle isomer undergoes fast pseudorotation at room temperature, but below about -50 degrees C, it becomes slow enough to affect the NMR line width. The rate parameters for this process were estimated from the carbon-13 spectra in methylene chloride solutions to be, k(p)(-100 degrees C) approximately 1.7 x 10(3) s(-)(1) and E(a) approximately 9.6 kJ/mol. The slow crown-saddle isomerization at room temperature (half-life of about one year) allows quantitative separation (by chromatography) of the two isomers and their separate investigation. When the alkanoyloxy side chains are sufficiently long both isomers are mesogenic (n >or= 4 for the saddle and n >or= 5 for the crown), exhibiting hexagonal columnar mesophases. The structure, dynamics, and mesomorphic properties of these mesophase were investigated by X-ray diffraction, optical polarizing microscopy, differential scanning calorimetry, and NMR. The lattice parameters of the crown and saddle mesophases of corresponding homologues are almost identical and increase monotonically with increasing length of the side chains. The clearing temperatures of the saddle isomers are consistently lower than those of the corresponding crowns. Within each series, the clearing temperatures are almost independent of the length of the side chains (156 to 170 degrees C for the crown and 115 to 148 degrees C for the saddle). The thermal and kinetic properties of the neat compounds lead to peculiar phase sequences, as observed in the polarizing microscope and in the DSC thermogram, involving repeated, back and forth, interconversion between the two isomers. Carbon-13 MAS NMR measurements of the crown and saddle mesophases of several homologues were carried out. The spectra of the crown mesophase exhibit dynamic features consistent with planar 3-fold molecular jumps about the column axes. A quantitative analysis for the CTV-8 crown homologue yielded the following Arrhenius parameters, A = 3.1 x 10(22)s(-)(1) and E(a) = 130.1kJ/mol. These unusually high values suggest that the barrier to the jump process is temperature dependent, decreasing with increasing temperature. The rate of this 3-fold jump process is slower for the lower homologues and faster for the higher ones. In contrast, the saddle isomers in the mesophase do not show dynamic effects in their carbon-13 MAS spectra. They do not undergo pseudorotation, and it appears that the molecules remain locked within the columns in a saddle conformation, up to the clearing temperature. However, on (super-)cooling to room temperature and below, selective line broadening is observed in their carbon-13 MAS spectra. This suggests that the saddle conformation is twisted in the mesophase and undergoes fast high-amplitude jumps between the twisted forms. On cooling, these high-amplitude librations freeze out to give an orientationally disordered state. On a very long time scale (of the order of days at 100 degrees C), the saddle mesophase transforms into that of the crown, apparently by sublimation.

Interrelation between hydration and interheadgroup interaction in phospholipids.

The stability and the ionic conductivity of biological membranes and of lipid bilayers depend on their hydration. A small number of water molecules adhere strongly to the different residues of the lipid headgroups and are oriented by them. An additional number of water molecules adhere more weakly, preserving their freedom of rotation, but are essential for bestowing the thermodynamic properties of hydrated bilayers and of biological membranes. Around six water molecules are attached so strongly to the headgroups of different phospholipids (PL) that they are rendered unfreezable, or their freezing is extended over such a wide range of temperatures that it cannot be detected by differential scanning calorimetry (DSC). If cholesterol is added to the PL above the concentration at which phase separation of the cholesterol phase occurs, the number of unfreezable water molecules per PL increases, indicating that the PL molecules on the border line between the two phases attach nearly twice as many water molecules as those in the middle of the phase. The orientation of about seven or eight water molecules attached to PL headgroups (seven to phosphatidyl serine (PS)) can be detected by polarized FTIR. The dichroic ratio of the successively adhering water molecules to the headgroup of PS fluctuates between 2.6 and 2.9, with the cumulative value of about 2.8 for the seven water molecules adhering to the headgroup of PS. In addition, in this case, the number of water molecules oriented by PL molecule residues on the border line of the two phases is much larger ( approximately 13 for PS). Interaction between two opposite negatively charged layers containing PS approaching each other may lead, after correlated electrostatic attraction, to change in the conformation of the headgroups with concomitant dehydration. This process is enhanced by Ca(+) and by Li(+), but it may also occur with Na(+) and K(+) as counter-ions if the layers are mutually aligned. This process may be important in the fusion mechanism of biological membranes, and its molecular modeling has been carried out.