Extending the Scope of the New Variant of the Castagnoli–Cushman Cyclocondensation onto o-Methyl Benzoic Acids Bearing Various Electron-Withdrawing Groups in the α-Position

Based on the previously reported involvement of homophthalic acid monoesters in the Castagnoli–Cushman reaction-type cyclocondensation with imines, we tested a number of other o-methyl benzoic acids bearing various electron-withdrawing groups in the α-position. The majority of these substrates delivered the expected tetrahydroisoquinolone adducts on activation with CDI or acetic anhydride. Homophthalic acid mononitriles displayed the highest promise as substrates for the new reaction, both in terms of scope and product yields. Homophthalic acid monoamides either gave low yields or failed to react with imines. Sulfonyl-substituted substrates gave the desired (and hitherto unknown) type of tetrahydroisoquinolines. Despite the low yields, this approach to sulfonyl-substituted tetrahydroisoquinolines appears practical as alternative syntheses based on the traditional, carboxylic acid CCR adducts would presumably be cumbersome and multistep. The azido- and nitro-substituted o-methyl benzoic acids failed to react with imines.     

2-Imidazoline Nitroxide Derivatives of Cymantrene

The 2-imidazoline nitroxide derivatives of cymantrene—2-(η⁵-cyclopentadienyl)tricarbonylmanganese(I)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-3-oxide-1-oxyl (NNMn) and 2-(η⁵-cyclopentadienyl)tricarbonylmanganese(I)-4,4,5,5-tetramethyl-4,5-dihydro-1H-imidazole-1-oxyl (INMn) were synthesized. It was shown that NNMn and INMn exhibit a sufficiently high kinetic stability both in solids and in solutions under normal conditions. Their structural characteristics, magnetic properties and electrochemical behavior are close to Re(I) analogs. This opens the prospect of using paramagnetic cymantrenes as prototypes in the design of Re(I) half-sandwiched derivatives for theranostics, where therapy is combined with diagnostics by magnetic resonance imaging due to the contrast properties of nitroxide radicals.     

α-Diimine Cisplatin Derivatives: Synthesis,Structure, Cyclic Voltammetry and Cytotoxicity

Three new Pt(II) complexes [(dpp-DAD)PtCl₂] (I), [(Mes-DAD(Me)₂)PtCl₂] (II) and [(dpp-DAD(Me)₂)PtCl₂] (III) were synthesized by the direct reaction of [(CH₃CN)₂PtCl₂] and corresponding redox-active 1,4-diaza-1,3-butadienes (DAD). The compounds were isolated in a single crystal form and their molecular structures were determined by X-ray diffraction. The purity of the complexes and their stability in solution was confirmed by NMR analysis. The Pt(II) ions in all compounds are in a square planar environment. The electrochemical reduction of complexes I–III proceeds in two successive cathodic stages. The first quasi-reversible reduction leads to the relatively stable monoanionic complexes; the second cathodic stage is irreversible. The coordination of 1,4-diaza-1,3-butadienes ligands with PtCl₂ increases the reduction potential and the electron acceptor ability of the DAD ligands. The synthesized compounds were tested in relation to an adenocarcinoma of the ovary (SKOV3).     

Synthesis of Cobalt Bis(Dicarbollide)—Curcumin Conjugates for Potential Use in Boron Neutron Capture Therapy

A series of novel cobalt bis(dicarbollide)—curcumin conjugates were synthesized. Two conjugates were obtained through the nucleophilic ring-opening reaction of the 1,4-dioxane and tetrahydropyran derivatives of cobalt bis(dicarbollide) with the OH group of curcumin, and using two equiv. of the oxonium derivatives, two other conjugates containing two cobalt bis(dicarbollide) units per molecule were obtained. In contrast to curcumin, the conjugates obtained were found to be non-cytotoxic against both tumor and normal cell lines. The analysis of the intracellular accumulation of the conjugates by flow cytometry showed that all cobalt bis(dicarbollide)—curcumin conjugates entered HCT116 colorectal carcinoma cells in a time-dependent manner. New non-cytotoxic conjugates contain a large amount of boron atoms in the biomolecule and can potentially be used for further biological research into boron neutron capture therapy (BNCT).     

Conjugates of Iron-Transporting N-Hydroxylactams with Ciprofloxacin

Screening of a library of novel N-hydroxylactams amenable by the Castagnoli-Cushman reaction identified four lead compounds that facilitated ⁵⁵Fe transport into P. aeruginosa cells (one of these synthetic siderophores was found to be as efficient at promoting iron uptake as the natural siderophores pyoverdine, pyochelin or enterobactin). Conjugates of the four lead siderophores with ciprofloxacin were tested for antibacterial activity against P. aeruginosa POA1 (wild type) and the ∆pvdF∆pchA mutant strain. The antibacterial activity was found to be pronounced against the ∆pvdF∆pchA mutant strain grown in CAA medium but not for the POA1 strain. This may be indicative of these compounds being ‘Trojan horse’ antibiotics. Further scrutiny of the mechanism of the antibacterial action of the newly developed conjugates is warranted.     

A finite volume cell‐centered Lagrangian hydrodynamics approach for solids in general unstructured grids

A finite volume cell‐centered Lagrangian hydrodynamics approach, formulated in Cartesian frame, is presented for solving elasto‐plastic response of solids in general unstructured grids. Because solid materials can sustain significant shear deformation, evolution equations for stress and strain fields are solved in addition to mass, momentum, and energy conservation laws. The total stress is split into deviatoric shear stress and dilatational components. The dilatational response of the material is modeled using the Mie‐Grüneisen equation of state. A predicted trial elastic deviatoric stress state is evolved assuming a pure elastic deformation in accordance with the hypo‐elastic stress‐strain relation. The evolution equations are advanced in time by constructing vertex velocity and corner traction force vectors using multi‐dimensional Riemann solutions erected at mesh vertices. Conservation of momentum and total energy along with the increase in entropy principle are invoked for computing these quantities at the vertices. Final state of deviatoric stress is effected via radial return algorithm based on the J‐2 von Mises yield condition. The scheme presented in this work is second‐order accurate both in space and time. The suitability of the scheme is evinced by solving one‐ and two‐dimensional benchmark problems both in structured grids and in unstructured grids with polygonal cells. Copyright © 2013 John Wiley & Sons, Ltd.