Crucigasterins A-E, antimicrobial amino alcohols from the Mediterranean colonial ascidian Pseudodistoma crucigaster

Five new unsaturated 2-amino-3-alcohols, crucigasterins A-E (2-6), were isolated together with known related compound 7 from the Mediterranean ascidian Pseudodistoma crucigaster and characterised as diacetyl derivatives (2a-6a) by spectroscopic methods. The threo-relative configuration of the amino alcohol portion was inferred by NOE analysis of the oxazolidinone derivative of crucigasterin A (2) as well as by ¹³C NMR comparison with synthetic threo and erythro model compounds. The co-occurring metabolites were assumed to have the same relative configuration as 2 by comparison of the diagnostic carbon value of C-1. The absolute stereochemistry of compound 7 that had not been previously reported was determined by applying the modified Mosher’s method on the corresponding N-acetyl derivative. The same absolute configuration was suggested for the other co-occurring crucigasterins by biogenetic considerations. Antibacterial and antifungal activities of selected crucigasterins were also evaluated.     

Modelling taxation and redistribution: A discrete active particle kinetic approach

In this paper a general framework is proposed, suitable for the modelling of the taxation and redistribution process in a closed society. This framework arises within a discrete kinetic approach for active particle systems, and is expressed by a system of nonlinear ordinary differential equations. It is intended to describe the evolution of the wealth distribution over the population, based on the interactions of single individuals. The framework is then employed towards the construction of a toy model, which is analytically and computationally investigated.     

Multitarget Drug Discovery for Alzheimer's Disease: Triazinones as BACE‐1 and GSK‐3β Inhibitors

Cumulative evidence strongly supports that the amyloid and tau hypotheses are not mutually exclusive, but concomitantly contribute to neurodegeneration in Alzheimer′s disease (AD). Thus, the development of multitarget drugs which are involved in both pathways might represent a promising therapeutic strategy. Accordingly, reported here in is the discovery of 6‐amino‐4‐phenyl‐3,4‐dihydro‐1,3,5‐triazin‐2(1H)‐ones as the first class of molecules able to simultaneously modulate BACE‐1 and GSK‐3β. Notably, one triazinone showed well‐balanced in vitro potencies against the two enzymes (IC₅₀ of (18.03±0.01) μM and (14.67±0.78) μM for BACE‐1 and GSK‐3β, respectively). In cell‐based assays, it displayed effective neuroprotective and neurogenic activities and no neurotoxicity. It also showed good brain permeability in a preliminary pharmacokinetic assessment in mice. Overall, triazinones might represent a promising starting point towards high quality lead compounds with an AD‐modifying potential.     

Slotted microcavity ring resonators for optical storage applications

In this paper, slotted microcavity ring resonators based optical storage devices are proposed and analyzed by means of multiresolution time domain technique. The effect of the structure geometrical parameters on the coupling efficiency, normalized transmission spectra and quality factor has been thoroughly investigated and compared to that of the conventional no-slot microring resonator. The suggested slotted configurations increase the quality factor at a fixed gap size between the central ring and input/output waveguides. In addition, the desired compromise between the coupling efficiency and resonance effect inside the ring can be achieved by mere optimization of the slot geometrical characteristics.     

n-channel polymers by design: optimizing the interplay of solubilizing substituents, crystal packing, and field-effect transistor characteristics in polymeric bithiophene-imide semiconductors

Electron transporting (n-channel) polymer semiconductors for field-effect transistors are rare. In this investigation, the synthesis and characterization of new electron-depleted N-alkyl-2,2'-bithiophene-3,3'-dicarboximide-based pi-conjugated homopolymers and copolymers containing the 2,2'-bithiophene unit are reported. A novel design approach is employed using computational modeling to identify favorable monomer properties such as core planarity, solubilizing substituent tailorability, and appropriate electron affinity with gratifying results. Monomeric model compounds are synthesized to confirm these properties, and a crystal structure reveals a short 3.43 A pi-pi stacking distance with favorable solubilizing substituent orientations. A family of 10 homopolymers and bithiophene copolymers is then synthesized via Yamamoto and Stille polymerizations, respectively. Two of these polymers are processable in common organic solvents: the homopolymer poly(N-(2-octyldodecyl)-2,2'-bithiophene-3,3'-dicarboximide) (P1) exhibits n-channel FET activity, and the copolymer poly(N-(2-octyldodecyl)-2,2':5',2':5',2'-quaterthiophene-3,3'-dicarboximide) (P2) exhibits air-stable p-channel FET operation. After annealing, P1 films exhibit a very high degree of crystallinity and an electron mobility > 0.01 cm (2) V(-1) s(-1) with a current on-off ratio of 10 (7), which is remarkably independent of film-deposition conditions. Extraordinarily, P1 films also exhibit terracing in AFM images with a step height matching the X-ray diffraction d spacing, a rare phenomenon for polymeric organic semiconductors. Another fascinating property of these materials is the air-stable p-channel FET performance of annealed P2 films, which exhibit a hole mobility of approximately 0.01 cm(2) V(-1) s(-1) and a current on-off ratio of 10(7).