Heterocyclic Rearrangement of 4,5,6,7-Tetrahydro-6,6-dimethyl-benzo[c][1,2,5]oxadiazol-4-one (Z)-Arylhydrazones into Corresponding 2-Aryl-4,5,6,7-tetrahydro-2H-benzo[d][1,2,3]triazol-4-one Oximes

The thermal base-catalysed and photochemical transformation (Boulton-Katritzky rearrangement) of the title tetrahydrobenzo[c][1,2,5]oxadiazoles to tetrahydro-2H-benzo[d][1,2,3]triazoles is studied. Attempts to induce analogous rearrangement in tetrahydro-2H-benzo[d][1,2,3]triazol-4-one arylhydrazones or oximes failed. Some CNDO/2 calculation are also carried out.     

Planar tetranuclear lanthanide clusters with the Dy4 analogue displaying slow magnetic relaxation

Two isostructural tetranuclear lanthanide clusters of general formula [Ln(III)(4)(μ(3)-OH)(2)(o-van)(4)(O(2)CC(CH(3))(3))(4)(NO(3))(2)]·CH(2)Cl(2)·1.5H(2)O (Ln = Gd (1) and Dy (2)) (o-van = 3-methoxysalicylaldehydato anion) are reported. The metallic cores of both complexes display a planar 'butterfly' arrangement. Magnetic studies show that both are weakly coupled, with 2 displaying probable SMM behaviour.     

2,4-Pentanediolate as an alkoxide/diketonate "hybrid" ligand and the formation of aluminum and zirconium derivatives

When 2,4-pentanediol (2,4-H(2)pd) is deprotonated, the resulting dianion (2,4-pd) serves as a type of "hybrid" ligand, i.e., an alkoxide that possesses structural features of a β-diketonate. 2,4-Pentanediol reacts with Al(O-s-Bu)(3) and Zr(O-i-Pr)(4) to form chelated multinuclear complexes. The aluminum-containing product is first isolated as the insoluble [Al(2,4-pd)(2,4-Hpd)](n); on sublimation, a hydrocarbon-soluble mixture of polymetallic species is generated. Mass spectral evidence suggests that both Al(4)(2,4-pd)(6) and Al(5)(2,4-pd)(7)(2,4-Hpd) are present. The zirconium complex is isolated as an adduct, [Zr(2,4-pd)(2)](2)·(2,4-H(2)pd). The pentanediolates decompose on heating to form Al(2)O(3) and ZrO(2). Unlike the mononuclear Al(acac)(3) and Zr(acac)(4) derivatives (acac = acetylacetonate), the formation of aggregates with the 2,4-pd ligand suggests that the latter has more coordinative flexibility. The geometries of several model aluminum complexes with oxygen donor ligands were studied with density functional theory methods. The optimized structures were used with the gauge, including atomic orbital (GIAO) method to calculate their (27)Al NMR magnetic shielding values for comparison with experiment.     

A small molecule discrimination map of the antibiotic resistance kinome

Kinase-mediated resistance to antibiotics is a significant clinical challenge. These enzymes share a common protein fold characteristic of Ser/Thr/Tyr protein kinases. We screened 14 antibiotic resistance kinases against 80 chemically diverse protein kinase inhibitors to map resistance kinase chemical space. The screens identified molecules with both broad and narrow inhibition profiles, proving that protein kinase inhibitors offer privileged chemical matter with the potential to block antibiotic resistance. One example is the flavonol quercetin, which inhibited a number of resistance kinases in vitro and in vivo. This activity was rationalized by determination of the crystal structure of the aminoglycoside kinase APH(2″)-IVa in complex with quercetin and its antibiotic substrate kanamycin. Our data demonstrate that protein kinase inhibitors offer chemical scaffolds that can block antibiotic resistance, providing leads for co-drug design.     

Pressure-driven flow in open fluidic channels

Arsenic is an element that exists naturally in many rocks and minerals around the world. It also accumulates in petroleum, shale, oil sands, and coal deposits as a result of biogeochemical processes, and it has been found in fly ash from the combustion of solid biofuels. Arsenic compounds in their organic and inorganic forms pose both a health and an environmental risk, and continue to be a challenge to the energy industry. The environmental fate and removal technologies of arsenic compounds are controlled to a large extent by their surface interactions with inorganic and organic adsorbents. We report thermodynamic binding constants, K(binding), from applying the triple-layer surface complexation model to adsorption isotherm and pH envelope data for dimethylarsinic acid (DMA) and p-arsanilic acid (p-AsA) on hematite and goethite. Ligand exchange reactions were constructed based on the interpretation of ATR-FTIR spectra of DMA and p-AsA surface complexes. Surface coverage of adsorbates was quantified in situ from the spectral component at 840 cm(-1). The best fit to the DMA adsorption data was obtained using outer-sphere complex formation, whereas for p-AsA, the best fit was obtained using two monodentate inner-sphere surface complexes. The significance of the results is discussed in relation to improving modeling tools used by environmental regulators and the energy sector for optimum control of arsenic content in fuels.     

Gram scale synthesis of the C(18)-C(34) fragment of amphidinolide C

The synthesis of the C(18)-C(34) fragment of amphidinolide C has been achieved via two routes, culminating in both the shortest (11 steps) and highest yielding (26% overall yield) approaches to this segment. The highly convergent approach will facilitate the synthesis of analogues, including the C(18)-C(29) fragment of amphidinolide F. Synthetic highlights include the selective methylation of a diyne, and the highly efficient use of a second generation cobalt catalyst in the Mukaiyama oxidative cyclization to form the trans-THF ring.     

Copper-catalyzed amidation of 2-phenylpyridine with oxygen as the terminal oxidant

The Cu(OAc)(2)-catalyzed, O(2)-mediated amidation of 2-phenylpyridine via C-H bond activation is reported. A variety of nitrogen reagents including sulfonamides, carboxamides, and anilines participate in the reaction in moderate to good yields.     

A general and convenient route to oxazolyl ligands

A diverse range of chiral and achiral oxazolyl ligands, which have many applications including catalysis and luminescent devices, are synthesized simply in three steps from readily available and inexpensive phenol and amino alcohol starting materials. The method can be applied to ligands with electron-donating/-withdrawing and sterically demanding/undemanding substituents, and can conveniently be scaled up to >25 g of product.     

Rapid spatial and temporal controlled signal delivery over large cell culture areas

Controlled chemical delivery in microfluidic cell culture devices often relies on slowly evolving diffusive gradients, as the spatial and temporal control provided by fluid flow results in significant cell-perturbation. In this paper we introduce a microfluidic device architecture that allows for rapid spatial and temporal soluble signal delivery over large cell culture areas without fluid flow over the cells. In these devices the cell culture well is divided from a microfluidic channel located directly underneath the chamber by a nanoporous membrane. This configuration requires chemical signals in the microchannel to only diffuse through the thin membrane into large cell culture area, rather than diffuse in from the sides. The spatial chemical pattern within the microfluidic channel was rapidly transferred to the cell culture area with good fidelity through diffusion. The cellular temporal response to a step-function signal showed that dye reached the cell culture surface within 45 s, and achieved a static concentration in under 6 min. Chemical pulses of less than one minute were possible by temporally alternating the signal within the microfluidic channel, enabling rapid flow-free chemical microenvironment control for large cell culture areas.     

A Kirkwood-Buff Derived Force Field for Aqueous Alkali Halides

A classical nonpolarizable force field is presented for the simulation of aqueous alkali halide solutions (MX), where M = Li(+), Na(+), K(+), Rb(+), Cs(+) and X = F(-), Cl(-), Br(-), I(-), and their interactions with biomolecules. The models are specifically designed to reproduce the experimental Kirkwood-Buff integrals, and thereby the solution salt activities, as a function of salt concentration. Additionally, we demonstrate that these models reasonably reproduce other experimental properties including ion diffusion constants, dielectric decrements, and the excess heats of mixing. The parameters are developed by considering the properties of aqueous NaX and MCl solutions using a previously established model for NaCl. Transferability of the parameters to other salts is then established by the successful simulation of additional aqueous salt solutions, KI and CsBr, not originally included in the parameterization procedure.