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Superelectrophiles: Formamides were designed that when treated with triflic anhydride would be transformed into superelectrophilic amidine dications. These dications were so electrophilic that they underwent in situ dealkylation by the triflate anion (see scheme; Tf = trifluoromethanesulfonyl). DFT calculations were used to determine the mechanistic details of the dealkylation reaction.

Hydrogenases are a group of enzymes that catalyze the reversible cleavage of molecular hydrogen and are present within aerobic and anaerobic bacteria, archaea and eucarya. [1] There are three distinct classes of hydrogenase with two of these classes containing iron-sulfur clusters; [NiFe]-hydrogenase contains nickel-iron-sulfur clusters while [FeFe]-hydrogenase contains iron-sulfur clusters only.

Inhibition of Itk potentially constitutes a novel, nonsteroidal treatment for asthma and other T-cell mediated diseases. In-house kinase cross-screening resulted in the identification of an aminopyrazole-based series of Itk inhibitors. Initial work on this series highlighted selectivity issues with several other kinases, particularly AurA and AurB. A template-hopping strategy was used to identify a series of aminobenzothiazole Itk inhibitors, which utilized an inherently more selective hinge binding motif. Crystallography and modeling were used to rationalize the observed selectivity. Initial exploration of the SAR around this series identified potent Itk inhibitors in both enzyme and cellular assays.