Supersymmetric dark matter and the extragalactic gamma ray background

We trace the origin of the newly determined extragalactic gamma-ray background from EGRET data to an unresolved population of blazars and neutralino annihilation in cold dark matter halos. Using results of high-resolution simulations of cosmic structure formation, we calculate composite spectra and compare with the EGRET data. The resulting best-fit value for the neutralino mass is m(chi) = 515(+110)(-75) GeV (systematic errors approximately 30%).     

Expansion of the glycosynthase repertoire to produce defined manno-oligosaccharides

Mutant endo-mannanases, in which the catalytic nucleophile has been replaced, function as glycosynthases in the synthesis of manno-oligosaccharides of defined lengths.     

Preparation and structure of high-chlorinated bornane derivatives for the quantification of toxaphene residues in environmental samples

Summary The HRGC-determination of Taxophene® residues in the presence of other chlorinated hydrocarbons with similar retention times is often difficult. This problem can satisfactorily be overcome by using purely isolated high-chlorinated bornane derivatives (7–17) as standard. The method is highly selective for measuring toxaphene in complex environmental matrices, such as fish, and can also be used for evaluating the changes in the relative distribution that may have resulted from bioaccumulation and environmental transformation.Dedicated to Professor Dr. Wilhelm Fresenius on the occasion of his 80th birthday     

Synthesis,Biological Evaluation,and Docking Studies of Antagonistic Hydroxylated Arecaidine Esters Targeting mAChRs

The muscarinic acetylcholine receptor family is a highly sought-after target in drug and molecular imaging discovery efforts aimed at neurological disorders. Hampered by the structural similarity of the five subtypes’ orthosteric binding pockets, these efforts largely failed to deliver subtype-selective ligands. Building on our recent successes with arecaidine-derived ligands targeting M₁, herein we report the synthesis of a related series of 11 hydroxylated arecaidine esters. Their physicochemical property profiles, expressed in terms of their computationally calculated CNS MPO scores and HPLC-logD values, point towards blood–brain barrier permeability. By means of a competitive radioligand binding assay, the binding affinity values towards each of the individual human mAChR subtypes hM₁–hM₅ were determined. The most promising compound of this series 17b was shown to have a binding constant towards hM₁ in the single-digit nanomolar region (5.5 nM). Similar to our previously reported arecaidine-derived esters, the entire series was shown to act as hM1R antagonists in a calcium flux assay. Overall, this study greatly expanded our understanding of this recurring scaffolds’ structure–activity relationship and will guide the development towards highly selective mAChRs ligands.     

Modulation of the MOP Receptor (μ Opioid Receptor) by Imidazo[1,2-a]imidazole-5,6-Diones: In Search of the Elucidation of the Mechanism of Action

The μ-opioid receptors belong to the family of G protein-coupled receptors (GPCRs), and their activation triggers a cascade of intracellular relays with the final effect of analgesia. Classical agonists of this receptor, such as morphine, are the main targets in the treatment of both acute and chronic pain. However, the dangerous side effects, such as respiratory depression or addiction, significantly limit their widespread use. The allosteric centers of the receptors exhibit large structural diversity within particular types and even subtypes. Currently, a considerable interest is aroused by the modulation of μ-opioid receptors. The application of such a technique may result in a reduction in the dose or even discontinuation of classical opiates, thus eliminating the side effects typical of this class of drugs. Our aim is to obtain a series of 1-aryl-5,6(1H)dioxo-2,3-dihydroimidazo[1,2-a]imidazole derivatives and provide more information about their activity and selectivity on OP3 (MOP, human mu opioid receptor). The study was based on an observation that some carbonyl derivatives of 1-aryl-2-aminoimidazoline cooperate strongly with morphine or DAMGO in sub-threshold doses, producing similar results to those of normal active doses. To elucidate the possible mechanism of such enhancement, we performed a few in vitro functional tests (involving cAMP and β-arrestin recruitment) and a radioligand binding assay on CHO-K1 cells with the expression of the OP3 receptor. One of the compounds had no orthosteric affinity or intrinsic activity, but inhibited the efficiency of DAMGO. These results allow to conclude that this compound is a negative allosteric modulator (NAM) of the human μ-opioid receptor.     

Influence of Open Chain and Cyclic Structure of Peptidomimetics on Antibacterial Activity in E. coli Strains

An efficient method for the synthesis of functionalized peptidomimetics via multicomponent Ugi reaction has been developed. The application of trifluoroethanol (TFE) as a reaction medium provided desired products with good yields. Further, using the developed cyclisation reaction, the obtained peptidomimetics were transformed into the cyclic analogues (diketopiperazines, DKPs). The goal of the performed studies was to revised and compare whether the structure of the obtained structurally flexible acyclic peptidomimetics and their rigid cycling analogue DKPs affect antimicrobial activity. We studied the potential of synthesized peptidomimetics, both cyclic and acyclic, as antimicrobial drugs on model E. coli bacteria strains (k12, R2–R4). The biological assays reveal that DKPs hold more potential as antimicrobial drugs compared to open chain Ugi peptidomimetics. We believe that it can be due to the rigid cyclic structure of DKPs which promotes the membrane penetration in the cell of studied pathogens. The obtained data clearly indicate the high antibiotic potential of synthesized diketopiperazine derivatives over tested antibiotics.     

Polarons in magnesium-doped lithium niobate crystals induced by femtosecond light pulses

Strong light-induced absorption has been observed in lithium niobate crystals doped with magnesium after application of femtosecond illumination. In this material there are no Nb-on-Li-site defects and hence no antisite polarons occur, but small free polarons close to the conduction band can be generated. The light-induced absorption observed is attributed to these polarons. For LiNbO₃:Mg, their decay times are about two orders of magnitude smaller than those of the Nb-on-Li-site polarons in undoped material. The results are relevant for a better understanding of the suppression of the so-called optical damage in these crystals and for their use in femtosecond applications.     

The Synthesis and Evaluation of Diethyl Benzylphosphonates as Potential Antimicrobial Agents

The impact of substituent at phenyl ring of diethyl benzylphosphonate derivatives on cytotoxic activity was studied. The organophosphonates were obtained based on developed palladium-catalyzed α, β-homodiarylation of vinyl esters protocol. The new synthetic pathway toward 1,2-bis(4-((diethoxyphosphoryl)methyl)phenyl)ethyl acetate was proposed which significantly improves the overall yield of the final product (from 1% to 38%). Several newly synthesized organophosphonates were tested as new potential antimicrobial drugs on model Escherichia coli bacterial strains (K12 and R2-R3). All tested compounds show the highest selectivity and activity against K12 and R2 strains. Preliminary cellular studies using MIC and MBC tests and digestion of Fpg after modification of bacterial DNA suggest that selected benzylphosphonate derivatives may have greater potential as antibacterial agents than typically used antibiotics such as ciprofloxacin, bleomycin and cloxacillin. These compounds are highly specific for pathogenic E. coli strains based on the model strains used and may be engaged in the future as new substitutes for commonly used antibiotics, which is especially important due to the increasing resistance of bacteria to various drugs and antibiotics.     

N‐(1‐Naphthyl­acetyl)­glycine phen­acyl ester and phen­acyl (1‐naphthyl­acetoxy)­acetate

The structures of the bichromophoric compounds N‐(1‐naphthyl­acetyl)­gly­cine phen­acyl ester, C₂₂H₁₉NO₄, (I), and its oxy­gen analogue, phen­acyl (1‐naphthyl­acetoxy)­acetate, C₂₂H₁₈O₅, (II), have been determined. The mol­ecules of (I) are held together by intermolecular N—H⋯O hydrogen bonds between the carbonyl and N—H groups, while compound (II) does not show any hydrogen bonding in the crystal.     

The role of stacking faults for the formation of shunts during potential‐induced degradation of crystalline Si solar cells

Mono‐ and multicrystalline solar cells have been stressed by potential‐induced degradation (PID). Cell pieces with PID‐shunts are imaged by SEM using the EBIC technique in plan view as well as after FIB cross‐section preparation. A linear shaped signature is found in plan‐view EBIC images at every potential‐induced shunt position on both mono‐ and multicrystalline solar cells. Cross‐sectional SEM and TEM images reveal stacking faults in a {111} plane. Combined TEM/EDX measurements show that the stacking faults are strongly decorated with sodium. Thus, the electric conductivity of stacking faults is assumed to arise under the influence of sodium ion movement through a high electric field across the SiN_x anti‐reflective layer, resulting in PID. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)