There continues to be a persistent, widespread gender gap in multiple STEM disciplines at all educational and professional levels: from the self-reported interest of pre-school aged students in scientific exploration, to the percentages of tenured faculty in these 10 disciplines, more men than women express an interest in science, a confidence in their scientific abilities, and ultimately more men than women decide to pursue scientific careers. Reported herein is an intensive outreach effort focused on addressing this

Given the current impact of SARS-CoV2 and COVID-19 on human health and the global economy, the development of direct acting antivirals is of paramount importance. Main protease (M Pro ), a cysteine protease that cleaves the viral polyprotein, is essential for viral replication. Therefore, M Pro is a novel therapeutic target. We identified two novel M Pro inhibitors, D-FFRCMKyne and D-FFCitCMKyne, that covalently modify the active site cysteine (C145) and determined cocrystal structures. Medicinal chemistry efforts led to SM141 and SM142, which adopt a unique binding mode within the M Pro active site. Notably, these inhibitors do not inhibit the other cysteine protease, papain-like protease (PL Pro ), involved in the life cycle of SARS-CoV2. SM141 and SM142 block SARS-CoV2 replication in hACE2 expressing A549 cells with IC 50 values of 8.2 and 14.7 nM. Detailed studies indicate that these compounds also inhibit cathepsin L (CatL), which cleaves the viral S protein to promote viral entry into host cells. Detailed biochemical, proteomic, and knockdown studies indicate that the antiviral activity of SM141 and SM142 results from the dual inhibition of M Pro and CatL. Notably, intranasal and intraperitoneal administration of SM141 and SM142 lead to reduced viral replication, viral loads in the lung, and enhanced survival in SARS-CoV2 infected K18-ACE2 transgenic mice. In total, these data indicate that SM141 and SM142 represent promising scaffolds on which to develop antiviral drugs against SARS-CoV2.

Reported herein is the effect of cyclodextrins on the rates of aqueous Diels Alder reactions of 9-anthracenemethanol with a variety of N-substituted maleimides. These reactions occurred under mild reaction conditions (aqueous solvent, 40 °C), and were most efficient for the reaction of N-cyclohexylmaleimide with a methyl-β-cyclodextrin additive (94% conversion in 24 hours). These results can be explained on the basis of a model wherein the cyclodextrins bind the hydrophobic substituents on the maleimides and activate the dienophile via electronic modulation of the maleimide double bond. The results reported herein represent a new mechanism for cyclodextrin-promoted Diels Alder reactions, and have significant potential applications in the development of other cyclodextrin-promoted organic transformations. Moreover, the ability to deplanarize polycyclic aromatic hydrocarbons (PAHs) under mild conditions, as demonstrated herein, has significant applications for PAH detoxification.

Improved selectivity and sensitivity using covalent fluorophore–cyclodextrin analogues resulted in 100% successful classification for five classes of analytes.