Masking the Bioactivity of Hydroxamic Acids by Coordination to Cobalt: Towards Bioreductive Anticancer Agents.

The clinical use of many potent anticancer agents is limited by their non-selective toxicity to healthy tissue. One of these examples is vorinostat (SAHA), a pan histone deacetylase inhibitor, which shows high cytotoxicity with limited discrimination for cancerous over healthy cells. In an attempt to improve tumor selectivity, we exploited the properties of cobalt(III) as a redox-active metal center through stabilization with cyclen and cyclam tetraazamacrocycles, masking the anticancer activity of SAHA and other hydroxamic acid derivatives to allow for the complex to reach the hypoxic microenvironment of the tumor.

Nanoscale Magnetic Arrays through Block Copolymer Templating of Polyoxometalates.

Magnetic nanoarrays promise to enable new energy-efficient computations based on spintronics or magnonics. In this work, we present a block copolymer-assisted strategy for fabricating ordered magnetic nanostructures on silicon and permalloy substrates. Block copolymer micelle-like structures were used as a template in which polyoxometalate (POM) clusters could assemble in an opal-like structure.

Flow-dependent regulation of rat mesenteric lymphatic vessel contractile response requires activation of endothelial TRPV4 channels.

Objectives: The objective of our study is to evaluate the involvement of the transient receptor potential vanilloid 4 (TRPV4) in the alteration of lymphatic pumping in response to flow and determine the signaling pathways involved.

Methods: We used immunofluorescence imaging and western blotting to assess TRPV4 expression in rat mesenteric lymphatic vessels. We examined inhibition of TRPV4 with HC067047, nitric oxide synthase (NOS) with L-NNA and cyclooxygenases (COXs) with indomethacin on the contractile response of pressurized lymphatic vessels to flow changes induced by a stepwise increase in pressure gradients, and the functionality of endothelial TRPV4 channels by measuring the intracellular Ca response of primary lymphatic endothelial cell cultures to the selective agonist GSK1016790A.

Intramolecular C-N bond activation by a transient boryl anion.

Using a flexible diamido framework, a bulky boron bromide has been prepared as a precusor to a boryl anion with an extremely wide N-B-N angle. Reduction of the compound with lithium metal resulted in intramolecular C-N bond activation and migration of an aryl group onto the boron centre. Reaction of the boron bromide with K[FeCp(CO)] resulted in nucleophilic reactivity of a carbonyl oxygen and the cooperative activation of CO.

One- and two-electron reductions of a bulky BODIPY compound.

The redox reaction between a bulky BODIPY and a magnesium(I) reducing agent leads to the formal one-electron reduction of the BODIPY, initially generating a dipyrromethene-centred radical compound that dimerises C-C bond formation. In contrast, reduction with magnesium anthracene leads to the formal two-electron reduction of the BODIPY, resulting in the formation of the corresponding anion.