Activation and Deactivation of a Robust Immobilized Cp*Ir-Transfer Hydrogenation Catalyst: A Multielement in Situ X-ray Absorption Spectroscopy Study

A highly robust immobilized [Cp*IrCl2]2 precatalyst on Wang resin for transfer hydrogenation, which can be recycled up to 30 times, was studied using a novel combination of X-ray absorption spectroscopy (XAS) at Ir L3-edge, Cl K-edge, and K K-edge. These culminate in in situ XAS experiments that link structural changes of the Ir complex with its catalytic activity and its deactivation. Mercury poisoning and “hot filtration” experiments ruled out leached Ir as the active catalyst. Spectroscopic evidence indicates the exchange of one chloride ligand with an alkoxide to generate the active precatalyst. The exchange of the second chloride ligand, however, leads to a potassium alkoxide–iridate species as the deactivated form of this immobilized catalyst. These findings could be widely applicable to the many homogeneous transfer hydrogenation catalysts with Cp*IrCl substructure

A Remote Arene-Binding Site on Prostate Specific Membrane Antigen Revealed by Antibody-Recruiting Small Molecules

Prostate specific membrane antigen (PSMA) is a membrane-bound glutamate carboxypeptidase overexpressed in many forms of prostate cancer. Our laboratory has recently disclosed a class of small molecules, called ARM-Ps (antibody-recruiting molecule targeting prostate cancer) that are capable of enhancing antibody-mediated immune recognition of prostate cancer cells. Interestingly, during the course of these studies, we found ARM-Ps to exhibit extraordinarily high potencies toward PSMA, compared to previously reported inhibitors. Here, we report in-depth biochemical, crystallographic, and computational investigations which elucidate the origin of the observed affinity enhancement. These studies reveal a previously unreported arene-binding site on PSMA, which we believe participates in an aromatic stacking interaction with ARMs. Although this site is composed of only a few amino acid residues, it drastically enhances small molecule binding affinity. These results provide critical insights into the design of PSMA-targeted small molecules for prostate cancer diagnosis and treatment; more broadly, the presence of similar arene-binding sites throughout the proteome could prove widely enabling in the optimization of small-molecule–protein interactions

Systematic assembly of the double molecular boxes: {Cs⊂[CpCo(CN)(3)](4)[Cp*Ru](3)} as a tridentate ligand

Cubic cage compounds composed of Co-CN-Ru linkages have been prepared which illustrate the following features: (i) new motifs for alkali metal ion complexation (i.e., cationic receptors for cations), (ii) a new family of triaza-metalloligands, and (iii) a double box-like cage. The cages are synthesized by the condensation of [CpCo(CN)(3)](−) and [Cp*Ru(NCMe)(3)](+) (cyclopentadienyl, Cp; pentamethylcyclopentadienyl, Cp*) the presence of Cs(+). The species {Cs⊂{[CpCo(CN)(3)](4)[Cp*Ru](4)}(+) and {Cs⊂{[CpCo(CN)(3)](4)[Cp*Ru](3)[Cp*Rh]}(2+) illustrate the box-completion reaction Cs ⊂ Co(4)Ru(3) + M (M = Cp*Rh(2+), Cp*Ru(+)). With the naked ion precursors [Na(NCMe)(6)](+) and [Fe(NCMe)(6)](2+), the box-completion reactions afforded {Na{Cs⊂[CpCo(CN)(3)](4)[Cp*Ru](3)]}(2)}(+) and {Fe{Cs⊂ [CpCo(CN)(3)](4)[Cp*Ru](3)]}(2)}(2+). These cages provide the first examples, to our knowledge, of the double-box motif