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The reaction pathways and kinetics of n-hexadecane hydroisomerization and hydrocracking were determined in the presence of each of three platinum-containing dual-function catalysts:  (a) Pt on a proprietary zeolite (Pt/Ζ), (b) Pt on silica−alumina (Pt/Si−Al), and (c) Pt on MCM-41 (Pt/MCM-41). The reaction networks were used to interpret differences in isomerization selectivity. The low isomerization selectivity observed in the presence of Pt/Si−Al was shown to be a consequence of changes in both relative isomerization/cracking rates and reaction pathways. Using the classical bifunctional reaction scheme, the changes in pathway were hypothesized to be consistent with changes in the relative concentrations of metal and acid sites (i.e., the metal−acid balance). On the basis of a recently proposed model of dual-function catalysis, the different observed pathways were subsequently shown to be those expected in two limiting case of the metal−acid balance. The simplified quantitative picture given here provides a preliminary basis for relating catalyst preparation variables to catalyst performance for dual-function catalysts.

A concise large-scale synthesis of 1, a new antimitotic agent is described. The key step was a one-pot Sonogashira crosscoupling of an aryl halide with a heteroaryl halide through an acetylene using the readily available 2-methyl-3-butyn-2-ol ( 7). An innovative approach for palladium removal was designed and successfully scaled-up on a multikilogram scale. The product was crystallized from the crude reaction mixture while keeping the residual palladium in the mother liquor by using Pd-scavenging agents such as N-acetylcysteine or thiourea.

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The highly exothermic nature of Reformatsky reagent formation and the reported unpredictability of the induction time for its formation pose challenging problems for scaling up Reformatsky reactions. A zinc-activation procedure using DIBAL-H was developed and investigated using reaction calorimetry along with subsequent parts of the process. This procedure was shown to have important advantages for scale-up relative to previous zinc activation methods, including an immediate start of Reformatsky reagent formation with addition-controlled reaction. Calorimetric analysis was especially useful in specifying quickly a suitable temperature for Reformatsky reagent formation. The process was scaled up successfully.

Glycosylation of viral proteins is required for the progeny formation and infectivity of virtually all viruses. It is increasingly clear that distinct glycans also play pivotal roles in the virus's ability to shield and evade the host's immune system. Recently, there has been a great advancement in structural identification and quantitation of viral glycosylation, especially spike proteins. Given the ongoing pandemic and the high demand for structure analysis of SARS-CoV-2 densely glycosylated spike protein, mass spectrometry methodologies have been employed to accurately determine glycosylation patterns. There are still many challenges in the determination of site-specific glycosylation of SARS-CoV-2 viral spike protein. This is compounded by some conflicting results regarding glycan site occupancy and glycan structural characterization. These are probably due to differences in the expression systems, form of expressed spike glycoprotein, MS methodologies, and analysis software. In this review, we recap the glycosylation of spike protein and compare among various studies. Also, we describe the most recent advancements in glycosylation analysis in greater detail and we explain some misinterpretation of previously observed data in recent publications. Our study provides a comprehensive view of the spike protein glycosylation and highlights the importance of consistent glycosylation determination.

Although multiple radioprotectors are currently being investigated preclinically for efficacy and safety, few studies have investigated concomitant metabolic changes. This study examines the effects of amifostine on the metabolic profiles in tissues of mice exposed to cobalt-60 total-body gamma-radiation. Global metabolomic and lipidomic changes were analyzed using ultra-performance liquid chromatography (UPLC) quadrupole time-of-flight mass spectrometry (QTOF-MS) in bone marrow, jejunum, and lung samples of amifostine-treated and saline-treated control mice. Results demonstrate that radiation exposure leads to tissue specific metabolic responses that were corrected in part by treatment with amifostine in a drug-dose dependent manner. Bone marrow exhibited robust responses to radiation and was also highly responsive to protective effects of amifostine, while jejunum and lung showed only modest changes. Treatment with amifostine at 200 mg/kg prior to irradiation seemed to impart maximum survival benefit, while the lower dose of 50 mg/kg offered only limited survival benefit. These findings show that the administration of amifostine causes metabolic shifts that would provide an overall benefit to radiation injury and underscore the utility of metabolomics and lipidomics to determine the underlying physiological mechanisms involved in the radioprotective efficacy of amifostine. This approach may be helpful in identifying biomarkers for radioprotective efficacy of amifostine and other countermeasures under development.

To date, the United States Food and Drug Administration (FDA) has approved four drugs to mitigate hematopoietic acute radiation syndrome and all four are repurposed radiomitigators. There are several additional drug candidates currently under evaluation that may also be helpful for use during a widespread emergency. One possible candidate is Ex-Rad, also known as ON01210, a chlorobenzyl sulfone derivative (organosulfur compound), which is a novel, small-molecule kinase inhibitor with demonstrated efficacy in the murine model. In this study, we have evaluated the metabolomic and lipidomic profiles in serum samples of nonhuman primates (NHPs) treated with Ex-Rad after exposure to ionizing radiation. Two different dose administration schedules (Ex-Rad I administered 24 and 36 h post-irradiation, and Ex-Rad II administered 48 and 60 h post-irradiation), were used and evaluated using a global molecular profiling approach. We observed alterations in biochemical pathways relating to inflammation and oxidative stress after radiation exposure that were alleviated in animals that received Ex-Rad I or Ex-Rad II. The results from this study lend credence to the possible radiomitigative effects of this drug possibly via a dampening of metabolism-based tissue injury, thus aiding in recovery of vital, radiation-injured organ systems.