Epoxidation of soybean oil in toluene with peroxoacetic and peroxoformic acids — kinetics and side reactions

The kinetics of the epoxidation of soybean oil and the extent of side reactions were studied at 40, 60, and 80 °C. Epoxidation was carried out in toluene with “in situ” formed peroxoacetic and peroxoformic acid and in the presence of an ion exchange resin as the catalyst. The reaction was found to be first‐order with respect to the double bond concentration. At higher temperatures and at higher conversions a deviation from the first‐order kinetics was observed. The rate constants for the epoxidation with peroxoacetic acid were 0.118 (h⁻¹) at 40 °C, 0.451 (h⁻¹) at 60 °C and 1.278 (h⁻¹) at 80 °C, while those for peroxoformic acid were 0.264, 0.734, and 1.250 (h⁻¹). The activation energy was found to be 54.7 kJ/mol for the epoxidation with peroxoacetic acid and 35.9 kJ/mol for that with peroxoformic acid. Three factors indicated that side reactions did not occur on a large scale: The absence of an OH band in the IR spectra, the formation of less than 2% of higher molecular weight products from gel permeation chromatography and the selectivity values between 0.9 and 1.     

Graduate Students and Federated Searching

In the fall of 2009 and spring of 2010, 20 New Mexico State University graduate students were interviewed using a “think-aloud” protocol to describe their experiences with a federated search tool. Students found federated searching to be most effective when looking for very specific information and article abstracts and least effective when searching general terms and resources other than journal articles (i.e., books, media). Students used the federated search tool and Google together to find relevant citations and full text journal articles. Students indicated that they were highly satisfied with federated search despite some doubt as to how the search worked and what library resources were included in the search.     

Clinical and Genetic Characteristics of Pediatric Patients with Hypophosphatasia in the Russian Population

(1) Hypophosphatasia (HPP) is a rare inherited disease caused by mutations (pathogenic variants) in the ALPL gene which encodes tissue-nonspecific alkaline phosphatase (TNSALP). HPP is characterized by impaired bone mineral metabolism due to the low enzymatic activity of TNSALP. Knowledge about the structure of the gene and the features and functions of various ALPL gene variants, taking into account population specificity, gives an understanding of the hereditary nature of the disease, and contributes to the diagnosis, prevention, and treatment of the disease. The purpose of the study was to describe the spectrum and analyze the functional features of the ALPL gene variants, considering various HPP subtypes and clinical symptoms in Russian children. (2) From 2014–2021, the study included the blood samples obtained from 1612 patients with reduced alkaline phosphatase activity. The patients underwent an examination with an assessment of their clinical symptoms and biochemical levels of TNSALP. DNA was isolated from dried blood spots (DBSs) or blood from the patients to search for mutations in the exons of the ALPL gene using Sanger sequencing. The PCR products were sequenced using a reagent BigDye Terminator 3.1 kit (Applied Biosystems). Statistical analysis was performed using the GraphPad Prism 8.01 software. (3) The most common clinical symptoms in Russian patients with HPP and two of its variants (n = 22) were bone disorders (75%), hypomyotonia (50%), and respiratory failure (50%). The heterozygous carriage of the causal variants of the ALPL gene was detected in 225 patients. A total of 2 variants were found in 27 patients. In this group (n = 27), we identified 28 unique variants of the ALPL gene, of which 75.0% were missense, 17.9% were frameshift, 3.6% were splicing variants, and 3.6% were duplications. A total of 39.3% (11/28) of the variants were pathogenic, with two variants being probably pathogenic, and 15 variants had unknown clinical significance (VUS). Among the VUS group, 28.6% of the variants (7/28) were discovered by us for the first time. The most common variants were c.571G > A (p.Glu191Lys) and c.1171del (Arg391Valfs*12), with frequencies of 48.2% (13/28) and 11% (3/28), respectively. It was found that the frequency of nonsense variants of the ALPL gene was higher (p < 0.0001) in patients with the perinatal form compared to the infantile and childhood forms of HPP. Additionally, the number of homozygotes in patients with the perinatal form exceeded (p < 0.01) the frequencies of these genotypes in children with infantile and childhood forms of HPP. On the contrary, the frequencies of the compound-heterozygous and heterozygous genotypes were higher (p < 0.01) in patients with infantile childhood HPP than in perinatal HPP. In the perinatal form, residual TNSALP activity was lower (p < 0.0005) in comparison to the infantile and childhood (p < 0.05) forms of HPP. At the same time, patients with the heterozygous and compound-heterozygous genotypes (mainly missense variants) of the ALPL gene had greater residual activity (of the TNSALP protein) regarding those homozygous patients who were carriers of the nonsense variants (deletions and duplications) of the ALPL gene. Residual TNSALP activity was lower (p < 0.0001) in patients with pathogenic variants encoding the amino acids from the active site and the calcium and crown domains in comparison with the nonspecific region of the protein.     

Anti-Melanoma Capability of Contactless Cold Atmospheric Plasma Treatment

In this study, we demonstrated that the widely used cold atmospheric plasma (CAP) jet could significantly inhibit the growth of melanoma cells using a contactless treatment method, The flow rate of helium gas was a key operational parameter to modulate electromagnetic (EM) effect on melanoma cells. Metal sheets with different sizes could be used as a strategy to control the strength of EM effect. More attractive, the EM effect from CAP could penetrate glass/polystyrene barriers as thick as 7 mm. All these discoveries presented the profound non-invasive nature of a physically based CAP treatment, which provided a solid foundation for CAP-based cutaneous/subcutaneous tumor therapy.     

Fatigue crack growth behavior of silica particulate reinforced epoxy resin composite

In the present work, fatigue crack growth tests of epoxy resin composite reinforced with silica particle under various R-ratios were carried out to investigate the effect of R-ratio on crack growth behavior and to discuss fatigue crack growth mechanism. Crack growth curves arranged by ΔK showed clear R-ratio dependence even under no crack closure, where the values of ΔK_th were 0.82 and 0.33 MPa √m for R = 0.1 and 0.7 respectively. However, crack growth curves arranged by K_max merged into almost one curve regardless of R-ratio, which indicated that crack growth behavior of the present composite was time-dependent. The value of K_max,th were in the range from 0.78 to 1.12 MPa √m. In situ crack growth observation revealed the crack growth mechanism: micro-cracking near the interface between silica particle and resin matrix occurs ahead of a main crack and then micro-cracks coalesce with a main crack to grow. The crack path was in the epoxy matrix, which was consistent with the time-dependent crack growth.     

Synthesis and Structural and Initial Cancer Cell Line Characterization of Organotin Polyesters from Dipicolinic Acid

The interfacial polymerization is employed to produce high polymer poly(ester ethers) from the reaction of the salt of dipicolinic acid and various organotin dihalides. They are rapidly synthesized with yield increasing as the length of the organotin alkyl chain increases. Infrared spectroscopy shows the formation of new bands derived from the Sn–O and Sn–O(CO) linkages. IR also shows that the products exist as a combination of molecular geometries about the tin atom. MALDI MS shows formation of ion fragment clusters to five and six units in length. The products show good inhibition of a variety of cancer cell lines including two pancreatic cancer cell lines.     

Optimization of LpxC Inhibitors for Antibacterial Activity and Cardiovascular Safety

UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) is a Zn²⁺ deacetylase that is essential for the survival of most pathogenic Gram-negative bacteria. ACHN-975 (N-((S)-3-amino-1-(hydroxyamino)-3-methyl-1-oxobutan-2-yl)-4-(((1R,2R)-2-(hydroxymethyl)cyclopropyl)buta-1,3-diyn-1-yl)benzamide) was the first LpxC inhibitor to reach human clinical testing and was discovered to have a dose-limiting cardiovascular toxicity of transient hypotension without compensatory tachycardia. Herein we report the effort beyond ACHN-975 to discover LpxC inhibitors optimized for enzyme potency, antibacterial activity, pharmacokinetics, and cardiovascular safety. Based on its overall profile, compound 26 (LPXC-516, (S)-N-(2-(hydroxyamino)-1-(3-methoxy-1,1-dioxidothietan-3-yl)-2-oxoethyl)-4-(6-hydroxyhexa-1,3-diyn-1-yl)benzamide) was chosen for further development. A phosphate prodrug of 26 was developed that provided a solubility of >30 mg mL⁻¹ for parenteral administration and conversion into the active drug with a t_1/2 of approximately two minutes. Unexpectedly, and despite our optimization efforts, the prodrug of 26 still possesses a therapeutic window insufficient to support further clinical development.     

Dextran and Polymer Polyethylene Glycol (PEG) Coating Reduce Both 5 and 30 nm Iron Oxide Nanoparticle Cytotoxicity in 2D and 3D Cell Culture

Superparamagnetic iron oxide nanoparticles are widely used in biomedical applications, yet questions remain regarding the effect of nanoparticle size and coating on nanoparticle cytotoxicity. In this study, porcine aortic endothelial cells were exposed to 5 and 30 nm diameter iron oxide nanoparticles coated with either the polysaccharide, dextran, or the polymer polyethylene glycol (PEG). Nanoparticle uptake, cytotoxicity, reactive oxygen species (ROS) formation, and cell morphology changes were measured. Endothelial cells took up nanoparticles of all sizes and coatings in a dose dependent manner, and intracellular nanoparticles remained clustered in cytoplasmic vacuoles. Bare nanoparticles in both sizes induced a more than 6 fold increase in cell death at the highest concentration (0.5 mg/mL) and led to significant cell elongation, whereas cell viability and morphology remained constant with coated nanoparticles. While bare 30 nm nanoparticles induced significant ROS formation, neither 5 nm nanoparticles (bare or coated) nor 30 nm coated nanoparticles changed ROS levels. Furthermore, nanoparticles were more toxic at lower concentrations when cells were cultured within 3D gels. These results indicate that both dextran and PEG coatings reduce nanoparticle cytotoxicity, however different mechanisms may be important for different size nanoparticles.