Selective Chromium(VI) Trapping by an Acetate-Releasing Coordination Polymer.

We report the high-capacity and selective uptake of Cr(VI) from water using the coordination polymer silver bipyridine acetate (SBA, [Ag(4,4'-bipy)][CH3CO2]·3H2O). Cr capture involves the release of acetate, and we have structurally characterized two of the product phases that form: silver bipyridine chromate (SBC, SLUG-56, [Ag(4,4'-bipy)][CrO4]0.5·3.5H2O) and silver bipyridine dichromate (SBDC, SLUG-57, [Ag(4,4'-bipy)][Cr2O7]0.5·H2O). SBA maintains a high Cr uptake capacity over a wide range of pH values (2-10), reaching a maximum of 143 mg Cr/g at pH 4. This Cr uptake capacity is one of the highest among coordination polymers. SBA offers the additional benefits of a one-step, room temperature, aqueous synthesis and its release of a non-toxic anion following Cr(VI) capture, acetate. Furthermore, SBA capture of Cr(VI) remains >97% in the presence of a 50-fold molar excess of sulfate, nitrate, or carbonate. We also investigated the Cr(VI) sequestration abilities of silver 1,2-bis(4-pyridyl)ethane nitrate (SEN, [Ag(4,4'-bpe)][NO3]) and structurally characterized the silver 1,2-bis(4-pyridyl)ethane chromate (SEC, SLUG-58, [Ag(4,4'-bpe)][CrO4]0.5) product. SEN was, however, a less effective Cr(VI) sequestering material than SBA.

Synthesis and Functionalization of Challenging meso-Substituted Aryl Bis-pocket Porphyrins Accessed via Suzuki-Miyaura Cross-Coupling.

Herein we report an investigation into the synthesis, metalation, and functionalization of bis-pocket porphyrins using the Suzuki-Miyaura cross-coupling reaction. Steric limitations to accessing bis-pocket porphyrins were overcome by using this Pd-catalyzed C-C-bond-forming strategy to introduce steric bulk after macrocyclization: 2,6-dibromo-4-trimethylsilybenzaldehyde was condensed with pyrrole, and a variety of boronic acids were coupled to the resulting porphyrin in up to 95% yield. Furthermore, we show that these porphyrins can be metalated with a variety of metals and sulfonated to create water-soluble bis-pocket porphyrins.

A water-soluble iron-porphyrin complex capable of rescuing CO-poisoned red blood cells.

We describe herein a small-molecule platform that exhibits key properties needed by an antidote for CO poisoning. The design features an iron-porphyrin complex with bulky substituents above and below the macrocyclic plane to provide a hydrophobic pocket for CO binding and to prevent the formation of inactive oxo-bridged dimers. Peripheral charged groups impart water solubility. We demonstrate that the Fe(II) complex of a porphyrin with 2,6-diphenyl-4-sulfophenyl meso substituents can bind CO, stoichiometrically sequester CO from carboxyhemoglobin, and rescue CO-poisoned red blood cells.

Discovery of 4-Piperazine Isoquinoline Derivatives as Potent and Brain-Permeable Tau Prion Inhibitors with CDK8 Activity.

Tau prions feature in the brains of patients suffering from Alzheimer's disease and other tauopathies. For the development of therapeutics that target the replication of tau prions, a high-content, fluorescence-based cell assay was developed. Using this high-content phenotypic screen for nascent tau prion formation, a 4-piperazine isoquinoline compound (1) was identified as a hit with an EC50 value of 390 nM and 0.04 K p,uu. Analogs were synthesized using a hypothesis-based approach to improve potency and in vivo brain penetration resulting in compound 25 (EC50 = 15 nM; K p,uu = 0.63). We investigated the mechanism of action of this series and found that a small set of active compounds were also CDK8 inhibitors.

Photoredox Cyanomethylation of Indoles: Catalyst Modification and Mechanism.

The direct cyanomethylation of indoles at the 2- or 3-position was achieved via photoredox catalysis. The versatile nitrile synthon is introduced as a radical generated from bromoacetonitrile, a photocatalyst, and blue LED as a light source. The mechanism of the reaction is explored by determination of the Stern-Volmer quenching constants. By combining photophysical data and mass spectrometry to follow the catalyst decomposition, the catalyst ligands were tuned to enable synthetically useful yields of radical coupling products. A range of indole substrates with alkyl, aryl, halogen, ester, and ether functional groups participate in the reaction, affording products in 16-90% yields. The reaction allows the rapid construction of synthetically useful cyanomethylindoles, products that otherwise require several synthetic steps.