A collection of ninety-one 3-(arylthiomethyl)isoxazole-4,5-dicarboxamides were prepared starting from dimethyl 3-(chloromethyl)isoxazole-4,5-dicarboxylate. The thioether moieties in these compounds were subsequently oxidized to give the corresponding 3-(arylsulfonylmethyl) isoxazole-4,5-dicarboxamides. By carefully controlling stoichiometry and reaction conditions, the C4 and C5 carbomethoxy groups could be differentially derivatized to carboxamides. A total of 182 trisubstituted isoxazoles are reported and deposited in the National Institutes of Health Molecular Repository; an 80 compound subset was evaluated for insecticidal activity.

It was well-observed that SARS-CoV-2 may cause a hypercoagulable state in hospitalized patients. Often these hospitalized patients exhibit severe upper respiratory symptoms with hypoxia, requiring high amounts of oxygen support. In this study, we report a young healthy 30-year-old woman with no medical problems, who experienced an embolic stroke due to an otherwise asymptomatic SARS-CoV-2 infection in July 2020. The patient presented to the emergency department after experiencing sudden slurred speech, dizziness, and acute left leg weakness during a social gathering on a river boat the day prior to admission. She also vomited once, non-bilious. The patient had no upper respiratory symptoms and had not been practicing social distancing nor wearing a mask. She did not have any sick contacts or significant travel history. Patient used oral contraceptives but never smoked. The workup included a Computed Tomography (CT) angiogram, an Magnetic Resonance Imaging (MRI) and an Magnetic Resonance Angiography (MRA) of the brain. It was significant for acute stroke with acute intraluminal thrombus causing partial occlusion of the distal basilar artery with left pontine stroke. Given that the onset of symptoms was greater than 4 hours, she was outside of the tissue Plasminogen Activator (tPA) administration window. Patient was also not a candidate for embolectomy as National Institute of Health Stroke Scale (NIHSS) was 3 and the occlusion was partial. SARS-CoV-2 PCR test was positive. D-Dimer level was elevated but CRP was normal. Echocardiogram was unremarkable. The patient had no history of autoimmune disorder. Patient was initially treated with antiplatelet medications aspirin and clopidogrel (Plavix). Her condition improved and she could ambulate with a front wheel walker and stand by to assist. She was discharged four days later with anticoagulation medication rivaroxaban (Xarelto) for 3 months. This case illustrates that patients with an otherwise asymptomatic SARS-CoV-2 infection may still suffer from complications of SARS-CoV-2. Do women on oral contraceptives have higher risk of arterial embolism when infected with SARS-CoV-2? More study is needed.

For DNA in solution, there have been two methods for measuring the helical periodicity. One method examines the ladder of discrete bands formed in the electrophoretic pattern of supercoiled DNA. Such a ladder is assumed to reflect the set of differently linked covalently closed molecules. The other method measures the lengths of partial nuclease digestions of DNA segments affixed to flat surfaces. Neither method, however, is able to measure the absolute handedness. X-ray diffraction of DNA oligonucleotides can determine the handedness, but the DNA must necessarily be crystallized. We have developed a new method for determining the helical parameters of a segment of DNA in solution. It is the first non-crystallographic method that can directly determine both the helical periodicity and the absolute handedness of DNA. The results obtained using this method are consistent with the classical Watson-Crick right-handed double helical model.

The synthesis of bisnitrile derivatives of benzobisimidazole and bibenzimidazole in a good yield is described in detail for the first time. Nucleophilic substitution of 1,5-difluoro-2,4-dinitrobenzene using different amines produced the intermediate diamines that were reduced using sodium borohydride/Pd(C) to produce the tetramines. These tetramines were allowed to couple with different aldehydes to produce the final benzimidazoles. In a different investigation, these bisnitrile derivatives will be used to make benzimidazole diamidines that could be used as potential mixed sequence minor groove binders.

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