Characterization of prednisolone in controlled porosity osmotic pump pellets using solid-state NMR spectroscopy.

The overall objective of this study was to demonstrate the influence of formulation and processing variables on the physical state of prednisolone (PDL) in formulations consisting of PDL, microcrystalline cellulose (MCC), and sulfobutylether-beta-cyclodextrin (CD). PDL was used as a model drug in controlled porosity osmotic pump pellet (CP-OPP) formulations, and was characterized using solid-state NMR spectroscopy and other complimentary analytical techniques. Dosage forms and the solid-state properties of drugs and excipients in a formulation may be influenced by the processing conditions used. Several processing parameters, such as amount of water used in wet granulation and subsequent drying conditions, were found to affect the solid-state transformation of PDL. In addition, the presence of excipients in the CP-OPP was observed to decrease the degree of PDL crystallinity, presumably by creating an inclusion complex with the CD. A hydrated form of PDL was created when PDL was ground with water alone; however, this form was not observed in formulated products. Solid-state NMR spectroscopy was shown to be a powerful technique for the analysis of drug formulations and investigations of the effects of processing conditions.

Epidemiology and outcome of nosocomial and community-onset bloodstream infection.

We performed a prospective study of bloodstream infection to determine factors independently associated with mortality. Between February 1999 and July 2000, 929 consecutive episodes of bloodstream infection at two tertiary care centers were studied. An ICD-9-based Charlson Index was used to adjust for underlying illness. Crude mortality was 24% (14% for community-onset versus 34% for nosocomial bloodstream infections). Mortality attributed to the bloodstream infection was 17% overall (10% for community-onset versus 23% for nosocomial bloodstream infections). Multivariate logistic regression revealed the independent associations with in-hospital mortality to be as follows: nosocomial acquisition (odds ratio [OR] 2.6, P < 0.0001), hypotension (OR 2.6, P < 0.0001), absence of a febrile response (P = 0.003), tachypnea (OR 1.9, P = 0.001), leukopenia or leukocytosis (total white blood cell count of <4500 or >20000, P = 0.003), presence of a central venous catheter (OR 2.0, P = 0.0002), and presence of anaerobic organism (OR 2.5, P = 0.04). Even after adjustments were made for underlying illness and length of stay, nosocomial status of bloodstream infection was strongly associated with increased total hospital charges (P < 0.0001). Although accounting for about half of all bloodstream infections, nosocomial bloodstream infections account for most of the mortality and costs associated with bloodstream infection.

Comparison of porphyrin-based, growth factor-based, and biochemical-based testing methods for identification of Haemophilus influenzae.

The accurate identification of Haemophilus spp. is essential for optimizing the role of the clinical microbiology laboratory in the diagnosis and management of Haemophilus infections. One laboratory-prepared medium and eight commercially available test systems were examined in parallel as a means of identifying 378 clinical isolates of Haemophilus spp. as either Haemophilus influenzae or non- Haemophilus influenzae spp. At least one discordant result was noted with 187 (49.5%) of the isolates tested. Discordant results were resolved either by majority rule for isolates with less than three discordant test results or by confirming the identity using conventional biochemical tests for isolates with three or more discordant test results ( n=20). Among these 20 isolates, 2 were judged not to belong to the Haemophilus genus. Comparisons of three porphyrin-based methods, three growth factor-based methods (1 of which also incorporates a porphyrin testing component), and three biochemical-based methods revealed varying discrepancy rates within each testing method. In general, porphyrin-based methods, with overall discrepancy rates of 1.3% or less, outperformed other testing methods. One important exception was the performance of the porphyrin testing component of the Haemophilus Identification Test Kit (Remel, USA), which produced an overall discrepancy rate of 28.5% and a false-negative rate of 52.2% with non- Haemophilus influenzae isolates. Growth factor-based methods yielded overall discrepancy rates ranging from 1.6% ( Haemophilus Identification Agar Quad; Remel) to 10.4% (hemin and nicotinamide adenine dinucleotide disk component of the Haemophilus Identification Test Kit). Biochemical-based assays produced overall discrepancy rates ranging from 4.5% (API NH; bioMérieux Vitek, USA) to 10.1% ( Neisseria Haemophilus Identification Card; bioMérieux Vitek). Collectively, these results suggest that porphyrin-based testing methods represent the most reliable means for identifying Haemophilus spp.

Interleukin-6 enhances production of anti-OspC immunoglobulin G2b borreliacidal antibody.

Protection against infection with Borrelia burgdorferi is dependent primarily on induction of complement-dependent antibody that can kill the spirochete. Measuring the production of sustained high levels of borreliacidal antibody is thus paramount for determining potential vaccine efficacy. We investigated the borreliacidal antibody response in sera and the amount of antibody produced by cultured lymph node cells of C3H/HeJ mice vaccinated with outer surface protein C (OspC). We showed that recombinant OspC was a weak stimulant of borreliacidal antibody production compared to whole cells of OspC-expressing B. burgdorferi. Mice vaccinated with B. burgdorferi in adjuvant produced a high level (titer, 5,120) of anti-OspC borreliacidal antibody, which waned rapidly. Similarly, borreliacidal antibody production by cultured lymph node cells from vaccinated mice peaked soon after vaccination and then decreased. Treatment of lymph node cells with interleukin-6 (IL-6) augmented borreliacidal antibody production, particularly immunoglobulin G2b, whereas treatment with anti-IL-6 inhibited the borreliacidal response. These findings demonstrate a previously unrecognized role for IL-6 in borreliacidal antibody production that may have important implications for vaccine development.

Production of borreliacidal antibody to outer surface protein A in vitro and modulation by interleukin-4.

Borreliacidal antibody production is one of several parameters for establishing the effectiveness of Borrelia burgdorferi vaccines. The production of borreliacidal antibody was studied in vitro by culturing immune lymph node cells with macrophages and B. burgdorferi. We showed that borreliacidal antibody, directed primarily against outer surface protein A (OspA), was readily produced by lymph node cells obtained from C3H/HeJ mice vaccinated with formalin-inactivated B. burgdorferi in aluminum hydroxide, but not recombinant OspA. Anti-OspA borreliacidal antibody was detected in supernatants of cultures of lymph node cells obtained on day 7 after vaccination, peaked on day 17, and rapidly declined. The borreliacidal activity was attributable to immunoglobulin G1 (IgG1), IgG2a, and IgG2b antibodies. When lymph node cells were treated with interleukin-4 (IL-4), production of borreliacidal antibody was inhibited but was unaffected by treatment with anti-IL-4 antibodies. These results suggest that other cytokines, but not IL-4, are mainly responsible for production of the secondary borreliacidal antibody response.

Nuclear magnetic resonance and infrared spectroscopic analysis of nedocromil hydrates.

PURPOSE: Nedocromil sodium (NS), which is used in the treatment of reversible obstructive airway diseases, such as asthma, has been found to exist in the following solid phases: the heptahemihydrate, the trihydrate, a monohydrate, an amorphous phase, which contains variable amounts of water, and a recently discovered methanol + water (MW) solvate. Our aim was to apply 13C solid-state nuclear magnetic resonance (NMR) spectroscopy and solid-state Fourier transform infrared (FTIR) spectroscopy to the study of specific interactions in the various solid forms of NS. METHODS: The 13C solid-state NMR and FTIR spectra of the various solid forms of NS were obtained and were related to the crystal structures of NS, the conformations of the nedocromil anion, and the interactions of the water molecules in these crystals. RESULTS: The 13C solid-state NMR spectrum is sensitive to the conformation of the nedocromil anion, while the solid-state FTIR spectrum is sensitive to interactions of water molecules in the solid state. In NS monohydrate, for which the crystal structure has not yet been solved, and in the amorphous phase, the information about the conformations of the nedocromil anion and the interactions of the water molecules are deduced from the 13C solid-state NMR spectra and solid-state FTIR spectra, respectively. CONCLUSIONS: 13C solid-state NMR spectroscopy and solid-state FTIR spectroscopy are shown to be powerful complementary tools for probing the chemical environment of molecules in the solid state, specifically the conformation of the nedocromil anion and the interactions of water-molecules, respectively.

Study of the conversion of methanol to dimethyl ether on zeolite HZSM-5 using in situ flow MAS NMR.

The conversion of methanol to gasoline (MTG) range hydrocarbons on zeolite catalyst HZSM-5 has been studied extensively using solid-state NMR. We have studied the reaction under batch and flow conditions using an isolated flow variable-temperature (VT) MAS NMR probe. This probe was developed to study heterogeneous catalysis reactions in situ at temperatures greater than 300 degrees C with reactant flow. In the batch studies, when 13C-labeled methanol was adsorbed on zeolite HZSM-5, sealed, and heated to 250 degrees C, dimethyl ether was formed. Two-dimensional exchange NMR shows that dimethyl ether was in equilibrium with methanol at 250 degrees C. When 13C-methanol was flowed over HZSM-5 at temperatures > or = 200 degrees C, only dimethyl ether was observed. Between 160 degrees C and 200 degrees C, both methanol and dimethyl ether were observed. The flow results are significant in that they suggest that there is no equilibrium between methanol and dimethyl ether in the catalyst at high temperatures, and that surface methoxy groups do not exist on the catalyst at high temperatures.

Occurrence of severe destructive lyme arthritis in hamsters vaccinated with outer surface protein A and challenged with Borrelia burgdorferi.

Arthritis is a frequent and major complication of infection with Borrelia burgdorferi sensu stricto. The antigens responsible for the induction of arthritis are unknown. Here we provide direct evidence that a major surface protein, outer surface protein A (OspA), can induce arthritis. Hamsters were vaccinated with 30, 60, or 120 microg of recombinant OspA (rOspA) in aluminum hydroxide and challenged with B. burgdorferi sensu stricto isolate 297 or C-1-11. Swelling of the hind paws was detected in 100, 100, and 50% of hamsters vaccinated with 30, 60, or 120 microg of rOspA, respectively. In addition, arthritis developed in 57% of hamsters vaccinated with a canine rOspA vaccine after infection with B. burgdorferi sensu stricto. When the canine rOspA vaccine was combined with aluminum hydroxide, all vaccinated hamsters developed arthritis after challenge with B. burgdorferi sensu stricto. Histopathologic examination confirmed the development of severe destructive arthritis in rOspA-vaccinated hamsters challenged with B. burgdorferi sensu stricto. These findings suggest that rOspA vaccines should be modified to eliminate epitopes of OspA responsible for the induction of arthritis. Our results are important because an rOspA vaccine in aluminum hydroxide was approved by the Food and Drug Administration for use in humans.

Flow cytometric testing of susceptibilities of Mycobacterium avium to amikacin, ciprofloxacin, clarithromycin and rifabutin in 24 hours.

OBJECTIVE: To develop a biologically safe flow cytometric susceptibility test that depends on detection and enumeration of actively growing Mycobacterium avium organisms in drug-free and antimycobacterial agent-containing medium. METHODS: Prior to analysis by flow cytometry, all M. avium susceptibility test samples were inactivated by exposure to paraformaldehyde. The susceptibilities of 20 clinical isolates of M. avium to amikacin, ciprofloxacin, clarithromycin, and rifabutin were tested by the flow cytometric and BACTEC methods. RESULTS: Agreement was 97% between the results of the two methods. The results of flow cytometric susceptibility tests were available 24 h after inoculation of drug-containing medium, while the BACTEC method required 4-8 days to complete. CONCLUSIONS: The flow cytometric assay is safe, simple and reproducible.

Macrophages interact with enriched populations of distinct T lymphocyte subsets for the induction of severe destructive Lyme arthritis.

Severe destructive Lyme arthritis was detected in the hind paws of hamsters infused with enriched populations of either CD4+ or CD4- T lymphocytes along with macrophages exposed in vitro to formalin-inactivated Borrelia burgdorferi and then infected with the Lyme spirochete. Swelling was detected 4 days after infection, increased rapidly, peaked on day 8 of infection, and gradually decreased. Similarly, severe destructive arthritis was induced in hamsters infused with enriched populations of unfractionated T lymphocytes and macrophages exposed to spirochetes after infection with B. burgdorferi. Histopathological examination affirmed that hamsters infused with CD4+, CD4-, or unfractionated T lymphocytes and macrophages exposed to B. burgdorferi-induced arthritis. In addition, macrophages exposed in vitro to B. burgdorferi demonstrated both conventional and coiling phagocytosis, suggesting a mechanism by which CD4+ and CD4- T lymphocytes induce arthritis, respectively. These findings demonstrate that both CD4+ and CD4- subpopulations of T lymphocytes are capable of interacting with macrophages for the induction of severe destructive Lyme arthritis.

Characterization of racemic species of chiral drugs using thermal analysis, thermodynamic calculation, and structural studies.

The identification of the racemic species, as a racemic compound, a racemic conglomerate, or a racemic solid solution (pseudoracemate), is crucial for rationalizing the potential for resolution of racemates by crystallization. The melting points and enthalpies of fusion of a number of chiral drugs and their salts were measured by differential scanning calorimetry. Based on a thermodynamic cycle involving the solid and liquid phases of the enantiomers and racemic species, the enthalpy, entropy and Gibbs free energy of the racemic species were derived from the thermal data. The Gibbs free energy of formation, is always negative for a racemic compound, if it can exist, and the contribution from the entropy of mixing in the liquid state to the free energy of formation is the driving force for the process. For a racemic conglomerate, the entropy of mixing in the liquid state is close to the ideal value of R ln 2 (1.38 cal.mol-1. K-1). Pseudoracemates behave differently from the other two types of racemic species. When the melting points of the racemic species is about 30 K below that of the homochiral species, is approximately zero, indicating that the racemic compound and racemic conglomerate possess similar relative stabilities. The powder X-ray diffraction patterns and 13C solid-state nuclear magnetic resonance spectra are valuable for revealing structural differences between a racemic compound and a racemic conglomerate. Thermodynamic prediction, thermal analysis, and structural study are in excellent agreement for identifying the nature of the racemic species.

Inhibition of the production of anti-OspA borreliacidal antibody with T cells from hamsters vaccinated against Borrelia burgdorferi.

The serious morbidity associated with Lyme borreliosis has focused considerable effort on the development of a comprehensive vaccine for protection against infection with Borrelia burgdorferi. Induction of borreliacidal antibody by vaccination or infection has been shown to correlate with protection of humans and animals against infection with the Lyme spirochete. In this report, we showed that high levels of borreliacidal antibody (titer of 1,280) were produced in vitro when T and B cells from hamsters 14 days after vaccination were incubated with macrophages and B. burgdorferi. By contrast, T and B cells from hamsters 7 or 21 days after vaccination failed to initiate production of borreliacidal activity. Furthermore, the T cells from hamsters 7 or 21 days after vaccination inhibited the in vitro production of borreliacidal antibody when cocultured with T and B cells obtained from hamsters 14 days after vaccination. When cell-free supernatants from the suspensions of T and B cells from hamsters 14 days after vaccination were absorbed with recombinant OspA, they lost nearly all borreliacidal activity. The removal of anti-OspA antibody resulted in a decrease in borreliacidal titer from 1,280 to less than 4. These results demonstrate that T cells from vaccinated animals can prevent a sustained production of protective borreliacidal antibody.

Solid-state characterization of two polymorphs of aspartame hemihydrate.

From the known crystal structure of aspartame hemihydrate, designated form 1, the theoretical powder X-ray diffraction (PXRD) pattern was calculated. This PXRD pattern differs significantly from that of the commercially available aspartame hemihydrate, which is therefore a different polymorph, designated form II. Form II transforms to form I during ball-milling or on heating for 30 min at 160 degrees C in the presence of steam. The two polymorphs were compared by PXRD, differential scanning calorimetry, thermogravimetric analysis, Karl Fischer titrimetry, Fourier transform infrared (FTIR) absorption spectroscopy, 13C solid-state nuclear magnetic resonance (SSNMR) spectroscopy, scanning electron microscopy, particle size analysis, and measurements of true density and intrinsic dissolution rate. Comparison of the 13C SSNMR and FTIR spectra of the two polymorphs suggests that the crystal structure of form II is less symmetric, with the side chains located in multiple environments. Although both hemihydrate polymorphs on heating in the absence of moisture dehydrate to a crystalline anhydrate, form I does so at a lower temperature, suggesting weaker interactions of water with aspartame molecules. At higher temperatures the anhydrate from both hemihydrate polymorphs yields 3-(carboxymethyl)-6-benzyl-2,5-dioxopiperazine (DKP) by a cyclization reaction for which the temperature, reaction enthalpy, and activation energy are very similar. Both hemihydrate forms, when in contact with liquid water, yield the 2.5-hydrate.

Hydration and dehydration behavior of aspartame hemihydrate.

Previous studies have shown that aspartame in the solid state can exist as a hemihydrate which occurs in two different polymorphic forms (I and II). The present work shows that equilibration of either hemihydrate at 25 degrees C with water vapor at relative humidities > or = 58% or with liquid water produces a 2.5-hydrate. Upon subjecting each of these crystalline hydrates to increasing temperature, the same crystalline anhydrate is formed which thermally cyclizes at a higher temperature to form the known compound 3-(carboxymethyl)-6-benzyl-2,5-dioxopiperazine. The activation energy of the cyclization reaction appears to depend on the degree of crystallinity of the anhydrate that is formed at a lower temperature. On increasing the temperature of the 2.5-hydrate, a hemihydrate intervenes before the anhydrate is formed. This intervening hemihydrate is similar to the commercial form (II) of aspartame hemihydrate but exhibits greater amorphous character. The techniques employed were Karl Fischer titrimetry, powder X-ray diffractometry, differential scanning calorimetry, thermogravimetric analysis, solid-state 13C nuclear magnetic resonance spectroscopy, and Fourier transform infrared absorption spectroscopy.

Physicochemical characterization of nedocromil bivalent metal salt hydrates. 2. Nedocromil zinc.

Salts are usually considered as alternatives for drug delivery when the physicochemical characteristics of the acidic or basic parent drug are unsuitable or inadequate for a satisfactory formulation. The physical, chemical, and biological characteristics of nedocromil sodium, which is used in the treatment of reversible obstructive airways diseases such as asthma, can be altered by its conversion to other salt forms. Nedocromil zinc (NZ), a bivalent metal salt, was found to exist in several hydration states, an octahydrate, a heptahydrate, and a pentahydrate, which itself exists in two modifications, designated as A and B. The relationships between these, NZ hydrates and the nature of the water interactions in the solid phases were studied through characterization by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Karl Fischer titrimetry (KFT), hot-stage microscopy (HSM), ambient- or variable-temperature powder X-ray diffraction (PXRD), Fourier-transform infrared (FTIR) spectroscopy, solid-state nuclear magnetic resonance (SSNMR) spectroscopy, environmental scanning electron microscopy (ESEM), water uptake at various relative humidities (RH), intrinsic dissolution rate (IDR), and solubility measurements. The integral water stoichiometries of the NZ hydrates were deduced from KFT and TGA and were confirmed by elemental analysis. For the heptahydrate, the loss of 1 mol of water at a higher temperature than for the others is attribute to an identifiable water molecule that is linked directly to the zinc and to two carboxylate oxygen atoms but not to the other water molecules, as deduced from the crystal structure previously determined. Similarly, for both pentahydrate modifications, 1 mol of water was also lost at a higher temperature than the others. Results from studies using DSC, TGA, HSM, PXRD, SSNMR, and FTIR suggested that the octahydrate contains loosely bound water in its structure and is partially amorphous. The course of the dehydration processes depended on the water vapor pressure and temperature. The octahydrate and heptahydrate underwent an apparently irreversible phase transformation to the pentahydrate at an elevated temperature and water vapor pressure. Pentahydrate modifications A and B differ in their long-range order (deduced from differences in their PXRD pattern and their thermal analytical behavior), but their short-range order (i.e., molecular environments) are identical (deduced by identical SSNMR spectra). The rank order of both IDR and solubility in water at 25 degrees C was octahydrate > heptahydrate > pentahydrate modification A approximately pentahydrate modification B, corresponding to the rank order of free energy with respect to the aqueous solution and the order of preparation according to Ostwald's rule of stages.

A Quantitative Method for Determination of Lactide Composition in Poly(lactide) Using (1)H NMR.

A method has been developed to quantitatively determine the composition of d-lactide and meso-lactide stereoisomer impurities in poly(lactide) containing predominantly l-lactide. In this method, the stereosequence information obtained from a few well-resolved resonances in the (1)H NMR spectrum representing RR and R stereogenic defects is used. The d-lactide and meso-lactide as minor components lead to RR and R stereogenic defects, respectively, which influence the isotactic chain length distribution and hence affect the polymer properties. Analytical equations relating the stereosequence probability to the lactide feed composition are not available due the complicated kinetics involved for the melt polymerization; viz. the preference for syndiotactic lactide addition decreases with reducing residual lactide concentration in the batch process. Hence, empirical correlations were determined by least-squares fit to the predictions for the specific stereosequence probabilities provided by Monte Carlo calculations of a number of lactide stereocopolymerizations. The Monte Carlo calculations simulate the kinetics observed for melt polymerization at 180 °C catalyzed by Sn(II) bis(2-ethylhexanoate) (Sn(II) octoate) in a 1:10 000 catalyst/lactide ratio.

Physicochemical characterization of nedocromil bivalent metal salt hydrates. 3. Nedocromil calcium.

A crystalline pentahydrate and a crystalline 8/3 hydrate of nedocromil calcium (NC) were prepared. The relationships between these solid phases and the nature of the water interactions in their structures were studied through characterization by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Karl Fischer titrimetry (KFT), hot-stage microscopy (HSM), ambient- or variable-temperature powder X-ray diffraction (PXRD), Fourier-transform infrared (FTIR) spectroscopy, solid-state nuclear magnetic resonance (SSNMR) spectroscopy, water uptake at various relative humidities (RH), intrinsic dissolution rate (IDR) and solubility measurements. The solubility and intrinsic dissolution rate of the pentahydrate in water at 25 degrees C are approximately 17% greater than the corresponding values for the 8/3 hydrate, corresponding to a greater Gibbs free energy of only 380 J.mol-1 (91 cal.mol-1) for the pentahydrate. The results of DSC, TGA, and FTIR and SSNMR spectroscopy indicate that the water of hydration is more loosely bound in the pentahydrate than in the 8/3 hydrate. On increasing the temperature in open-pan DSC and TGA, the water in the pentahydrate is released in four steps (three steps in crimped pans), whereas the water in the 8/3 hydrate is released in three steps (three steps also in crimped pans). These three stepwise dehydrations are fundamentally explained by their different water environments in the crystal structure of the 8/3 hydrate, which was determined by single-crystal XRD [crystal data: triclinic, space group P1, a = 13.2381(3) A, b = 13.3650(2) A, c = 17.8224(2) A, alpha = 68.202(1) degrees, beta = 86.894(1) degrees, gamma = 82.969(1) degrees, Z = 6]. The asymmetric unit contains three nedocromil anions and three calcium cations associated with eight water molecules. The nedocromil anions act as polyfunctional ligands to the Ca2+ ions, coordinating through both the carbonyl oxygen and the carboxylate oxygen atoms. The molecular conformations of the three nedocromil anions in the asymmetric unit are almost identical. However, the crystal structure contains two different calcium environments, one of which has the Ca2+ ion hydrated by four water molecules in the equatorial plane and by two carbonyl oxygens in its axial coordination sites. In the second environment, the Ca2+ ion has four carboxylate oxygen atoms in its equatorial plane and two water molecules in its axial coordination sites. Two of the carboxylate ligands are twisted out of the tricyclic ring, and the other two carboxylate ligands are nearly coplanar with the tricyclic ring. All of the eight water molecules in the 8/3 hydrate are linked to calcium and carboxylate ions and none are linked to other water molecules.

Physicochemical characterization of nedocromil bivalent metal salt hydrates. 1. Nedocromil magnesium.

Nedocromil sodium is used in the treatment of reversible obstructive airways diseases, such as asthma. The physicochemical, mechanical, and biological characteristics of nedocromil sodium can be altered by its conversion to other salt forms. In this study, three crystalline hydrates, the pentahydrate, heptahydrate, and decahydrate, of a bivalent metal salt, nedocromil magnesium (NM), were prepared. The relationships between these hydrates were studied through their characterization by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA). Karl Fischer titrimetry (KFT), hot stage microscopy (HSM), ambient or variable temperature powder X-ray diffraction (PXRD), Fourier-transform infrared (FTIR) spectroscopy, solid-state nuclear magnetic resonance (SSNMR) spectroscopy, scanning electron microscopy (SEM), water uptake at various relative humidities (RH), intrinsic dissolution rate (IDR), and solubility measurements. The pentahydrate showed two dehydration steps, corresponding to two binding states of water, a more temperature-sensitive tetramer and a more stable monomer, deduced from the crystal structure previously determined. The heptahydrate and decahydrate each showed a dehydration step with a minor change in slope at about 50 degrees C, which was analyzed by derivative TGA and confirmed by DSC. HSM and variable temperature PXRD also confirmed the thermal dehydration behavior of the NM hydrates. The decahydrate underwent an apparently irreversible phase transformation to the pentahydrate at 75 degrees C at an elevated water vapor pressure. The PXRD, FTIR, and SSNMR of the decahydrate were similar to those of the heptahydrate, suggesting that the three extra water molecules in the decahydrate are loosely bound, but were significantly different from those of the pentahydrate. The rank order of both IDR and solubility in water at 25 degrees C was heptahydrate approximately decahydrate > pentahydrate, corresponding to the rank order of free energy with respect to the aqueous solution.

Synthesis of Linear Acetylenic Carbon: The "sp" Carbon Allotrope.

A carbon allotrope based on "sp" hybridization containing alternating triple and single bonds (an acetylenic or linear carbon allotrope) has been prepared. Studies of small (8 to 28 carbon atoms) acetylenic carbon model compounds show that such species are quite stable (130 degrees to 140 degrees C) provided that nonreactive terminal groups or end caps (such as tert-butyl or trifluoromethyl) are present to stabilize these molecules against further reactions. In the presence of end capping groups, laser-based synthetic techniques similar to those normally used to generate fullerenes, produce thermally stable acetylenic carbon species capped with trifluoromethyl or nitrile groups with chain lengths in excess of 300 carbon atoms. Under these conditions, only a negligible quantity of fullerenes is produced. Acetylenic carbon compounds are not particularly moisture or oxygen sensitive but are moderately light sensitive.