Conformational flexibility in the peripheral site of Torpedo californica acetylcholinesterase revealed by the complex structure with a bifunctional inhibitor

The X-ray crystallographic structure of Torpedo californica acetylcholinesterase (TcAChE) in complex with the bifunctional inhibitor NF595, a potentially new anti-Alzheimer drug, has been solved. For the first time in TcAChE, a major conformational change in the peripheral-site tryptophan residue is observed upon complexation. The observed conformational flexibility highlights the dynamic nature of protein structures and is of importance for structure-based drug design.     

Tributyltin(IV) Butyrate: A Novel Epigenetic Modifier with ER Stress- and Apoptosis-Inducing Properties in Colon Cancer Cells

Organotin(IV) compounds are a class of non-platinum metallo-conjugates exhibiting antitumor activity. The effects of different organotin types has been related to several mechanisms, including their ability to modify acetylation protein status and to promote apoptosis. Here, we focus on triorganotin(IV) complexes of butyric acid, a well-known HDAC inhibitor with antitumor properties. The conjugated compounds were synthesized and characterised by FTIR spectroscopy, multi-nuclear (¹H, ¹³C and ¹¹⁹Sn) NMR, and mass spectrometry (ESI-MS). In the triorganotin(IV) complexes, an anionic monodentate butyrate ligand was observed, which coordinated the tin atom on a tetra-coordinated, monomeric environment similar to ester. FTIR and NMR findings confirm this structure both in solid state and solution. The antitumor efficacy of the triorganotin(IV) butyrates was tested in colon cancer cells and, among them, tributyltin(IV) butyrate (BT2) was selected as the most efficacious. BT2 induced G2/M cell cycle arrest, ER stress, and apoptotic cell death. These effects were obtained using low concentrations of BT2 up to 1 μM, whereas butyric acid alone was completely inefficacious, and the parent compound TBT was poorly effective at the same treatment conditions. To assess whether butyrate in the coordinated form maintains its epigenetic effects, histone acetylation was evaluated and a dramatic decrease in acetyl-H3 and -H4 histones was found. In contrast, butyrate alone stimulated histone acetylation at a higher concentration (5 mM). BT2 was also capable of preventing histone acetylation induced by SAHA, another potent HDAC inhibitor, thus suggesting that it may activate HDACs. These results support a potential use of BT2, a novel epigenetic modulator, in colon cancer treatment.     

Determination of trace level of selenium and mercury in photographic emulsions by atomic spectroscopy techniques

Trace level of selenium and mercury in photographic emulsion are used to improve photographic properties. The presence of silver halide in photographic emulsion does not allow the application of the most common analytical methods such as Hydride Generation Atomic Absorption Spectrometry (HG-AAS) and cold vapour Atomic Absorption Spectrometry (CV-AAS). Besides, silver removal was not quantitative, leading to a significant loss of the analytes and low reproducibility. The present work suggest the use of inductively coupled plasma Atomic Emission Spectrometry (ICP-AES) equipped with Ultrasonic Nebulizer (USN) for direct aqueous samples analysis at microgram l-1 level (d.l. 5.1 ppb for Hg and 6.1 ppb for Se).     

On Complete Arcs Arising from Plane Curves

We point out an interplay between -Frobenius non-classical plane curves and complete -arcs in . A typical example that shows how this works is the one concerning an Hermitian curve. We present some other examples here which give rise to the existence of new complete -arcs with parameters and being a power of the characteristic. In addition, for q a square, new complete -arcs with either and or and are constructed by using certain reducible plane curves.     

On the number of anisotropic simple submodules in modules with a form

Let G be a finite group, and V a finite-dimensional semisimple G-module over a finite field. Assume that V is endowed with a nonsingular bilinear form which is symmetric or symplectic, and which is invariant under the action of G. In this setting, we compute the number of anisotropic simple submodules of V.Received: 25 May 2004     

On the Violation of Ohm’s Law for Bounded Interactions: a One Dimensional System

We consider an infinite Hamiltonian system in one space dimension, given by a charged particle subjected to a constant electric field and interacting with an infinitely extended system of particles. We discuss conditions on the particle/medium interaction which are necessary for the charged particle to reach a finite limiting velocity. We assume that the background system is initially in an equilibrium Gibbs state and we prove that for bounded interactions the average velocity of the charged particle increases linearly in time. This statement holds for any positive intensity of the electric field, thus contradicting Ohms law.Work partially supported by the GNFM-INDAM and the Italian Ministry of the University.     

Stereoselective synthesis of tetrasubstituted 2,3-dihydrofurans by one-step cyclization of beta-ketosulfides of benzothiazole and aldehydes in ionic liquids

A stereoselective synthesis of tetrasubstituted 2,3-dihydrofurans was carried out in n-butylpyridinium tetrafluoroborate ([bpy(+)][BF(4)(-)]) as solvent. The reaction proceeds smoothly in one step starting from simple materials such as aldehydes and beta-ketosulfides of benzothiazole. A comparison between several ionic liquids (ILs) is presented, and the role of the benzothiazolyl moiety is discussed. Workup proved to be very easy and recycling of IL possible.     

Polymer-supported haloarene chromium dicarbonyl isonitrile complexes: a study of their synthesis and reactivity

Different arene Cr(CO)(3) complexes were supported on a polystyrene isonitrile resin by photochemical-promoted replacement of a chromium carbonyl ligand by the NC group. The supported complexes proved to be stable and were successfully used for further transformations. In particular, the reactivity of dichlorobenzene complexes to different nucleophiles was investigated and found to be comparable with that of the parent Cr(CO)(3) complexes.     

Activated bond-breaking processes preempt the observation of a sharp glass-glass transition in dense short-ranged attractive colloids

We study-using molecular dynamics simulations-the temperature dependence of the dynamics in a dense short-ranged attractive colloidal glass to find evidence of the kinetic glass-glass transition predicted by the ideal mode coupling theory. According to the theory, the two distinct glasses are stabilized, one by excluded volume and the other by short-ranged attractive interactions. By studying the density autocorrelation functions, we discover that the short-ranged attractive glass is unstable. Indeed, activated bond-breaking processes slowly convert the attractive glass into the hard-sphere one, preempting the observation of a sharp glass-glass transition.