Multifunctional Small Molecules as Potential Anti-Alzheimer’s Disease Agents

Alzheimer’s disease (AD) is a severe multifactorial neurodegenerative disorder characterized by a progressive loss of neurons in the brain. Despite research efforts, the pathogenesis and mechanism of AD progression are not yet completely understood. There are only a few symptomatic drugs approved for the treatment of AD. The multifactorial character of AD suggests that it is important to develop molecules able to target the numerous pathological mechanisms associated with the disease. Thus, in the context of the worldwide recognized interest of multifunctional ligand therapy, we report herein the synthesis, characterization, physicochemical and biological evaluation of a set of five (1a–e) new ferulic acid-based hybrid compounds, namely feroyl-benzyloxyamidic derivatives enclosing different substituent groups, as potential anti-Alzheimer’s disease agents. These hybrids can keep both the radical scavenging activity and metal chelation capacity of the naturally occurring ferulic acid scaffold, presenting also good/mild capacity for inhibition of self-Aβ aggregation and fairly good inhibition of Cu-induced Aβ aggregation. The predicted pharmacokinetic properties point towards good absorption, comparable to known oral drugs.     

On the domain decomposition method for the generalized Stokes problem with continuous pressure

Using the nonoverlapping domain decomposition approach, we propose a formulation of the dual Schur algorithm for the generalized Stokes problem discretized by a mixed finite element method continuous for the pressure in each subdomain, but discontinuous at the interfaces. The corresponding LBB condition is checked. The dual interface problem is written in the case of two subdomains, and it is generalized to several subdomains. An efficient preconditioner for the interface problem is derived. Numerical results are presented for two different local solvers. Parallel computations were made on an IBM‐SP2. © 2000 John Wiley & Sons, Inc. Numer Methods Partial Differential Eq 16: 84–106, 2000     

Mathematical basis of approximate MO theories: Origin of mulliken's magic formula

The mathematical basis for the Ruedenberg's and Mulliken's approximations is given in a general framework.     

Smart hydrogels for Novel Optical Functions

Nanocomposites of inherently conductive polyaniline (PANI) within a highly hydrophilic polyvinyl alcohol (PVA) based hydrogel have been produced by coupling a conventional dispersion chemical oxidative polymerization to a subsequent high energy irradiation step, in order to convert the polymer stabilizing the aqueous dispersion, namely the PVA, into a highly water swollen hydrogel incorporating the PANI particles. The incorporation of the electroactive and “pH-sensitive” polymer into a transparent and highly permeable hydrogel matrix has been pursued as a route to the development of a novel class of potentially biocompatible, smart hydrogels that can respond to changes of the surrounding environment with measurable changes in their optical properties. Absorption spectra show that the optical absorption bands typical of PANI, known to be reversibly affected by changes of the polymer oxidation state or pH or both, are well preserved in the PVA hydrogels. Even more interestingly, fluorescence is observed from the nanoparticles of PANI in its inherently conductive form, whose intensity is strongly affected by changes of pH. This has enhanced the importance of this material to a large extent from both a scientific and a practical point of view.     

Synthesis and characterization of Si/Ga Eni Carbon Silicates

Phenylene-gallosilicates were prepared with the same crystalline structure as their aluminum ana-logues. The new Ga-Eni Carbon Silicates (Ga-ECS) phases were investigated by X-ray diffraction, scanning electron microscopy, nuclear magnetic resonance and thermogravimetric analysis, which demonstrated that gallium isomorphously replaced aluminum in the framework of the organ-ic-inorganic hybrids similar to the case of classical zeolites. Hybrid ECS materials were obtained with different types of bridged silsesquioxane precursors that maintained the aluminum-silicate nature of the inorganic moiety. This work confirms a new level of crystal chemistry versatility for this class of materials, and demonstrates the possibility to tailor also the inorganic part of the framework by changing the nature of the trivalent heteroatom.     

Tyrosine or Tryptophan? Modifying a Metalloradical Catalytic Site by Removal of the Cys–Tyr Cross-Link in the Galactose 6-Oxidase Homologue GlxA

The concerted redox action of a metal ion and an organic cofactor is a unique way to maximize the catalytic power of an enzyme. An example of such synergy is the fungal galactose 6-oxidase, which has inspired the creation of biomimetic copper oxidation catalysts. Galactose 6-oxidase and its bacterial homologue, GlxA, possess a metalloradical catalytic site that contains a free radical on a covalently linked Cys–Tyr and a copper atom. Such a catalytic site enables for the two-electron oxidation of alcohols to aldehydes. When the ability to form the Cys–Tyr in GlxA is disrupted, a radical can still be formed. Surprisingly, the radical species is not the Tyr residue but rather a copper second-coordination sphere Trp residue. This is demonstrated through the introduction of a new algorithm for Trp-radical EPR spectra simulation. Our findings suggest a new mechanism of free-radical transfer between aromatic residues and that the Cys–Tyr cross-link prevents radical migration away from the catalytic site.