Synthesis of Migrastatin Analogues as Inhibitors of Tumour Cell Migration: Exploring Structural Change in and on the Macrocyclic Ring

Migrastatin and isomigrastatin analogues have been synthesised in order to contribute to structure–activity studies on tumour cell migration inhibitors. These include macrocycles varying in ring size, functionality and alkene stereochemistry, as well as glucuronides. The synthesis work included application of the Saegusa–Ito reaction for regio‐ and stereoselective unsaturated macroketone formation, diastereoselective Brown allylation to generate 9‐methylmigrastatin analogues and chelation‐induced anomerisation to vary glucuronide configuration. Compounds were tested in vitro against both breast and pancreatic cancer cell lines and inhibition of tumour cell migration was observed in both wound‐healing (scratch) and Boyden chamber assays. One unsaturated macroketone showed low affinity for a range of secondary drug targets, indicating it is at low risk of displaying adverse side effects.     

Structural basis for the potential antitumour activity of DNA-interacting benzo[kl]xanthene lignans

The biological properties and possible pharmacological applications of benzo[kl]xanthene lignans, rare among natural products and synthetic compounds, are almost unexplored. In the present contribution, the possible interaction of six synthetic benzo[kl]xanthene lignans and the natural metabolite rufescidride with DNA has been investigated through a combined STD-NMR and molecular docking approach, paralleled by in vitro biological assays on their antiproliferative activity towards two different cancer cell lines: SW 480 and HepG2. Our data suggest that the benzo[kl]xanthene lignans are suitable lead compounds for the design of DNA selective ligands with potential antitumour properties.     

Synthesis and characterization of 2-phenylaniline cyclopalladated complexes

Reaction of the dinuclear complex [Pd{κ2-N2′,C1-2-(2′-NH₂C₆H₄)C₆H₄}Cl]₂ (1) with ligands (L = 4-picoline, sym-collidine) gave the six-membered palladacycles [Pd{κ2-N2′,C1-2-(2′-NH₂C₆H₄)C₆H₄}Cl(L)] (2). The complex 1 reacted with AgX (X = CF₃SO₃, BF₄) and bidentate ligands [L–L = phen (phenanthroline), dppe (bis(diphenylphosphino)ethane), bipy(2,2′-bipyridine) and dppp (bis(diphenylphosphino)propane)] giving the mononuclear orthopalladated complexes [Pd{κ2-N2′,C1-2-(2′-NH₂C₆H₄)C₆H₄}(L–L)] (3) [L–L = phen, dppe, bipy and dppp]. These compounds were characterized by physico-chemical methods, and the structure of [Pd{κ2-N2′,C1-2-(2′-NH₂C₆H₄)C₆H₄}Cl(L)] (L = sym-collidine) was determined by single-crystal X-ray analysis.     

Temperature-dependent fluorescence of cu(5) metal clusters: a molecular thermometer

The heat is on: A Cu(5) metal cluster presents distinctive photophysical properties that result in a temperature-dependent fluorescent quantum yield and excited-state lifetime between -45 and +80?°C, both in solution and as a solid. Unprecedented accuracy in temperature determination by fluorescence measurements was achieved with this complex, thus making it suitable for applications in, for example, biology and (nano)materials research.     

Synthesis,Characterization and Crystal Structure of Tetrabutylbis(4,5-dimethoxy-2-nitro benzoato)Distannoxane Dimer

Abstract  

Reaction of di-n-butyltin oxide with 4,5-dimethoxy-2-nitrobenzoic acid yields the title compound which crystallizes as the usual dicarboxylatotetraorganodistannoxane dimer. Experimental details for the preparation and the structural characterization (by FTIR, NMR and single crystal XRD) are provided. The IR data shows that ligand acts in the bidentate manner. The crystal structure analysis of the compound reveals the presence of a centrosymmetric planar Sn₂O₂ unit connected to exocyclic Sn atom via two bidentate bridging carboxylate ligands. The remaining two carboxylate ligands are coordinated to the exocyclic Sn atom in the monodentate manner.     

Continuity in finite time of entropy solutions for nonconvex conservation laws with reaction term

The aim of the paper is to study qualitative properties of entropy solutions to the Cauchy problem for the following reaction-convection equation with nonconvex flux f In particular we prove that under suitable assumptions the solution is continuous for large t.New resultsconcerning the asymptotic behavior of solutions are also given, proving convergence to a suitable combination of traveling profiles with different speeds.     

Data processing for image-based chemical sensors: unsupervised region of interest selection and background noise compensation

Natural olfaction suggests that numerous replicas of small sensors can achieve large sensitivity. This concept of sensor redundancy can be exploited by use of optical chemical sensors whose use of image sensors enables the simultaneous measurement of several spatially distributed indicators. Digital image sensors split the framed scene into hundreds of thousands of pixels each corresponding to a portion of the sensing layer. The signal from each pixel can be regarded as an independent sensor, which leads to a highly redundant sensor array. Such redundancy can eventually be exploited to increase the signal-to-noise ratio. In this paper we report an algorithm for reduction of the noise of pixel signals. For this purpose, the algorithm processes the output of groups of pixels whose signals share the same time behavior, as is the case for signals related to the same indicator. To define these groups of pixels, unsupervised clustering, based on classification of the indicator colors, is proposed here. This approach to signal processing is tested in experiments on the chemical sensitivity of replicas of eight indicators spotted on to a plastic substrate. Results show that the groups of pixels can be defined independently of the geometrical arrangement of the sensing spots, and substantial improvement of the signal-to-noise ratio is obtained, enabling the detection of volatile compounds at any location on the distributed sensing layer.     

Regularized formulation of the variational brittle fracture with unilateral contact: Numerical experiments

This paper presents a modified regularized formulation of the Ambrosio-Tortorelli type to introduce the crack non-interpenetration condition in the variational approach to fracture mechanics proposed by Francfort and Marigo [1998. Revisiting brittle fracture as an energy minimization problem. J. Mech. Phys. Solids 46 (8), 1319-1342]. We focus on the linear elastic case where the contact condition appears as a local unilateral constraint on the displacement jump at the crack surfaces. The regularized model is obtained by splitting the strain energy in a spherical and a deviatoric parts and accounting for the sign of the local volume change. The numerical implementation is based on a standard finite element discretization and on the adaptation of an alternate minimization algorithm used in previous works. The new regularization avoids crack interpenetration and predicts asymmetric results in traction and in compression. Even though we do not exhibit any gamma-convergence proof toward the desired limit behavior, we illustrate through several numerical case studies the pertinence of the new model in comparison to other approaches.