In the present work, we show for the first time that the conversion of aldehydes to alcohols can be achieved using “unprotected” iridium transfer hydrogenation catalysts inside living cells. The reactions were observed in real time by confocal fluorescence microscopy using a Bodipy fluorogenic substrate. We propose that the reduced cofactor nicotinamide adenine dinucleotide (NADH) is a possible hydride source inside the cell based on studies using pyruvate as a cellular redox modulator. We expect that this biocompatible reductive chemistry will be broadly useful to practitioners working at the interface of chemistry and the life sciences.

We demonstrate, for the first time, that pentamethylcyclopentadienyl (Cp*) iridium pyridinecarboxamidate complexes (5) can promote catalytic hydride transfer from nicotinamide adenine dinucleotide to aldehydes in pH 7.4 buffered cell growth media at 37 °C and in the presence of various biomolecules and metal ions. Stoichiometric hydride transfer studies suggest that the unique reactivity of 5, compared to other common Cp*Ir complexes, is at least in part due to the increased hydride transfer efficiency of its iridium hydride species 5-H. Complex 5 exhibits excellent reductase enzyme-like activity in the hydrogenation of cytotoxic aldehydes that have been implicated in a variety of diseases.Keywords: biocatalysis; biomimetic; bioorthogonal chemistry; detoxification; iridium catalysis; transfer hydrogenation

•Pt(II) and Pt(IV) complexes inhibit angiogenesis in human umbilical vein endothelial cells.•Phosphaplatins reduce the tumor size in tumor-xenografted mice.•A possible new class of anticancer agents against cisplatin-resistant tumors.Phosphaplatins are platinum-based antitumor compounds that, unlike other clinically utilized platinum drugs (i.e. cisplatin, carboplatin, and oxaliplatin), appear to target proteins rather than DNA. Because of their unique mode of action, phosphaplatins are promising drug candidates for cisplatin-resistant cancers. In this study, we discovered that Pt(II) and Pt(IV) phosphaplatins possess diverse antitumor properties. In addition to targeting apoptosis antigen (FAS) and proapoptotic gene products as described previously, phosphaplatins also target angiogenesis. We demonstrate that phosphaplatins inhibit human umbilical vein endothelial cell (HUVEC) migration and tube formation in vitro and suppress tumor angiogenesis and growth in immunodeficient mice that were inoculated with A2780 ovarian cancer cells in vivo. To provide insight into this novel antitumor mechanism, phosphaplatin-treated HUVECs were found to exhibit lower gene expression levels of vascular endothelial growth factors (VEGFs) and the VEGFR-2 receptor compared to untreated cells. Kinase inhibition studies suggest that phosphaplatins are inhibitors of VEGFR-2. In ligand exchange experiments using both Pt atomic absorption and 31P NMR spectroscopies, we show that phosphaplatins most likely bind to VEGFR-2 through metal-ligand coordination rather than electrostatic interactions. These studies enhance our understanding of the diverse and novel mechanisms of action of the phosphaplatin antitumor agents, which could potentially be used as chemotherapeutic agents against cisplatin-resistant cancers.The platinum agents phosphaplatin exhibit anti-cancer mechanisms that are different from those of the classical platinum drug cisplatin. The following work demonstrates that phosphaplatin can induce anti-angiogenesis in both in vitro and in vivo experiments. Phosphaplatin downregulates gene expression of growth factors/receptors and can bind to protein targets.

To gain a better understanding of the influence of cationic additives on coordination–insertion polymerization and to leverage this knowledge in the construction of enhanced olefin polymerization catalysts, we have synthesized a new family of nickel phenoxyimine–polyethylene glycol complexes (NiL0, NiL2–NiL4) that form discrete molecular species with alkali metal ions (M+ = Li+, Na+, K+). Metal binding titration studies and structural characterization by X-ray crystallography provide evidence for the self-assembly of both 1:1 and 2:1 NiL:M+ species in solution, except for NiL4/Na+ which form only the 1:1 complex. It was found that upon treatment with a phosphine scavenger, these NiL complexes are active catalysts for ethylene polymerization. We demonstrate that the addition of M+ to NiL can result in up to a 20-fold increase in catalytic efficiency as well as enhancement in polymer molecular weight and branching frequency compared to the use of NiL without coadditives. To the best of our knowledge, this work provides the first systematic study of the effect of secondary metal ions on metal-catalyzed polymerization processes and offers a new general design strategy for developing the next generation of high performance olefin polymerization catalysts.

An iridium(III) pentamethylcyclopentadienyl catalyst supported by 6,6′-dihydroxy-2,2′-bipyridine displays exquisite selectivity in acceptorless alcohol dehydrogenation of cyclic α,β-unsaturated alcohols over benzylic and aliphatic alcohols under mild aqueous reaction conditions. Hydrogenation of aldehydes and ketones occurs indiscriminately using the same catalyst under hydrogen, although chemoselectivity could be achieved when other potentially reactive carbonyl groups present are sterically inaccessible. This chemistry was demonstrated in the reversible hydrogenation and dehydrogenation of the A ring of glucocorticoids, despite the presence of other alcohol/or carbonyl functionalities in rings C and D. NMR studies suggest that an iridium(III) hydride species is a key intermediate in both hydrogenation and dehydrogenation processes.