Aβ-binding molecules: Possible application as imaging probes and as anti-aggregation agents

As amyloid β (Aβ) is at the centre of pathogenesis of Alzheimer's disease (AD), Aβ aggregate-specific probes for in vivo studies of Aβ are potentially important for the early diagnosis and the assessment of new treatment strategies in the AD brain by noninvasive imaging. Several series of compounds derived from Congo red (CR) and Thioflavin T (ThT) have been evaluated as potential probes for the Aβ imaging. They include a diversity of core structures contributing to their affinities to Aβ. Small-molecule inhibi- tors were known to inhibit the formation of Aβ oligomers and fibrils. This inhibition has to be performed in such a way that these inhibitors bind to Aβ in the binding channel where Aβ-binding probes should sit. Therefore, several of them were used as novel core structures to develop Aβ probes, with their de- rivatives exhibiting good Aβ affinities. This approach will facilitate the design of a variety of candidates for Aβ probe molecules and anti-aggregation-therapeutic drugs. Moreover, the finding of Aβ probes with diverse core structures recognized by binding sites on Aβs will likely provide a promising per- spective for the design of 99mTc-labeled probe-derived molecules.     

Kekulé structures as graph generators

Kekulé valence-bond structures of catacondensed conjugated hydrocarbons with no, one, two and three branched cycles (which may be 4-, 6- and/or 8-membered) are used to generate highly regular vertex-transitive graphs through the application of an equivalence relation to the sextet of -electrons in theterminal rings of the hydrocarbon. The partitioning of a given set of Kekulé structures allows the study of certain novel combinatorial aspects of Kekulé counts. The graph- generating character reported here is closely related to the recent work of Randi, Woodworth, Kleiner and Hosoya.     

Dichloro‐cyanoacetimidates as Glycosyl Donors

Transformation of 1‐O‐unprotected glucose and galactose derivatives (1a–d) into O‐glycosyl dichloro‐cyanoacetimidates (2a–d) was performed with dichloro‐cyanoacetonitrile in the presence of DBU as base. Reaction with different acceptors (3a–d) under TMSOTf catalysis afforded glycosides 4 in high yields. Competition experiments with O‐glucopyranosyl trichloroacetimidate 10a, bearing a 4‐tert‐butylbenzyl group at 6‐O, and O‐glucopyranosyl dichloro‐cyanoacetimidate 10b, bearing a 4‐methylbenzyl group at 6‐O, displayed similar reactivities for these two types of glycosyl donors.     

α-L-Arabinofuranosylated pyrrolidines as arabinanase inhibitors

As part of continued efforts to understand the mechanisms of 1,5-α-l-arabinanases better, some arabinan-like iminosugar oligosaccharides were synthesized. An iminosugar analogue of arabinobiose was found to be a good inhibitor of the arabinanase Arb93A from Fusarium graminearum. Structures were determined for complexes of this inhibitor with wild-type Arb93A and a catalytically inactive mutant.     

Non-hemolytic α-AApeptides as antimicrobial peptidomimetics

We report a new class of peptide mimetics, α-AApeptides, that display broad-spectrum activity against both Gram-negative and Gram-positive bacteria and fungi. With non-hemolytic activity, resistance to protease hydrolysis, and easy sequence programmability, α-AApeptides may emerge as a novel class of antibiotics.     

Why Are Selenouracils as Basic as but Stronger Acids than Uracil in the Gas Phase?

The gas‐phase basicity and acidity of 2‐selenouracil ( 2SU ), 4‐selenouracil ( 4SU ), and 2,4‐diselenouracil ( 24SU ) have been calculated at the B3LYP/6‐311+G(3df,2p) level of theory. Our results showed that all these compounds behave as bases of moderate strength in the gas phase. As was found for uracil and for the thiouracil analogues, the most basic site is the heteroatom at position 4, and only for 2SU is there a certain ambiguity in assigning the basic site. More importantly, with the only exception of 2SU , selenouracils are as basic as or slightly less basic than uracil, because the replacement of the oxygen atom at position 2 by a selenium atom leads to an increase of the electron delocalization inside the six‐membered ring, which decreases the intrinsic basicity of the heteroatom at position 4. As already reported for uracil and thiouracils, for selenouracils N1 is the most acidic site. However, selenouracils are predicted to be stronger acids than uracil. This acidity enhancement is essentially due to a specific stabilization of the anion when O is replaced by Se. Two factors are responsible for this stabilization: a significant aromatization of the ring upon deprotonation and a better dispersion of the excess electron density when the system contains third‐row atoms.     

Explosions as a Synthetic Tool? Cycloalkynes as Precursors to Fullerenes,Buckytubes, and Buckyonions

A provacative question is asked by the title. Explosions will probably not become a general synthetic method, but strained dehydrobenzoannulenes decompose explosively upon heating to give, inter alia, structured, fullerenoid carbon particles. The spectacular thermochemical behavior of these cycloalkynes has fueled hopes that acetylenic cyclophanes such as 1 can be prepared and brought to coalesce to spherical forms of carbon like the fullerenes. Promising progress in this area has recently been made and is highlighted in this contribution.     

Synthesis of Tetrahydropyridinyltriazolothiadiazines as Possible Muscarinic Agonists

4-Amino-5-(pyridin-3-yl)-4H-l,2,4-triazole-3-thiol 1 were condensed with 2-bromo-l-(substituted phenyl)ethanone to give pyridinyltriazolothiadiazines 2a-c, which were quaternarized with methyl iodide and oxidized with 30 % hydrogen peroxide to afford the corresponding methyl pyridinium salts 3a-c and pyridine- 1 -oxides 4a-c, respectively. The redtiction of compounds 3 and 4 with NaBH4 in methanol produced the target compounds 1-methyl- 1.2.5.6-tetrahydropyridin-3-yl)-6-aryl-s-triazolothiadiazines 5a-c and 3-( l-hydroxyl- 1, 2, 5, 6-tetrahydropyridin -3-yl)-6-aryl-s-triazolothiadiazines 6a-c, respectively. The endothelium vascular relaxing activity of the target compounds was screened.     

Oligophenylenaminones as scaffolds for α-helix mimicry

The design and synthesis of small molecule α-helix mimetics has been a productive field over the past decade. These compounds have performed well in a variety of biological systems as functional disruptors of α-helix-mediated protein-protein interactions. In our studies we have continued to develop novel, more biologically compatible scaffolds, which are often easier to assemble and capable of mimicking longer and/or more diverse helices. To this end, we have constructed a new series of i, i+4, i+7 α-helix mimics based on the enaminone scaffold. These molecules represent a step forward in the pursuit of idealized monofacial α-helix mimetics.     

Catalytical oxidation of styrene by molecularly imprinted polymer with phenylacetic acid as template and hemin as co-monomer

This letter used the molecular imprinting technology to build up the microenvironment around co-monomer bemin to mimic the cytochrome P450 catalyzing the epoxidation of styrene.The results showed that the conversion rates of products were obviously enhanced by molecularly imprinted polymers,compared to free hemin solution,using three kinds of oxidants.The used axial ligand in polymers synthesis also improved the total conversion rates.     

α-Sulfur crystals as a visible-light-active photocatalyst

We show that in contrast to conventional compound photocatalysts, α-sulfur crystals of cyclooctasulfur (S(8)) are a visible-light-active elemental photocatalyst. The α-S crystals were found to have the ability not only to generate ·OH radicals but also to split water in a photoelectrochemical process under both UV-vis and visible-light irradiation. Although the absolute activity obtained was low because of the large particle size and poor hydrophilicity of the α-S crystals studied, there is great potential for increasing the activity with the assistance of known strategies such as surface modification, nanoscaling, doping, and coupling with other photocatalysts.     

beta-peptides as catalysts: poly-beta-leucine as a catalyst for the Juliá-Colonna asymmetric epoxidation of enones

Poly-beta-leucines have been evaluated as catalysts for the Juliá-Colonna asymmetric epoxidation of enones; the beta 3-isomer was found to be an effective catalyst for the epoxidation of chalcone (70% ee) and some analogues.     

β-Lactam derivatives as potential anti-cancer compounds

A number of 1,4-diaryl-3-methylene substituted β-lactams, the addition products obtained from their reactions with N-, S-, and C-nucleophiles, and diverse related compounds were prepared, and a selection of 43 compounds was screened in preliminary tests as anti-tumor compounds by using 4 or 5 human cancer cell lines of diverse origins. Twelve compounds were highly active against all cell lines, 6 showed low activity, 12 no activity, and 13 exhibited a selective activity against a human small cell lung carcinoma cell line. Correspondence: Hans-Hartwig Otto, Department of Pharmaceutical/Medicinal Chemistry (PMC), Institute of Pharmacy, Ernst-Moritz-Arndt-University, 17487 Greifswald, Germany.     

β-Lactam derivatives as potential anti-cancer compounds

A number of 1,4-diaryl-3-methylene substituted β-lactams, the addition products obtained from their reactions with N-, S-, and C-nucleophiles, and diverse related compounds were prepared, and a selection of 43 compounds was screened in preliminary tests as anti-tumor compounds by using 4 or 5 human cancer cell lines of diverse origins. Twelve compounds were highly active against all cell lines, 6 showed low activity, 12 no activity, and 13 exhibited a selective activity against a human small cell lung carcinoma cell line.     

Microencapsulation of n-Eicosane as Energy Storage Material

For heat energy storage application, polynrea microcapsules containing phase change material, n-eicosane, were synthesized by using interfacial polymerization method with toluene-2,4-diisocyanate (TDI) and diethylenetriamine(DETA) as monomers in an emulsion system. Poly(ethylene glycol)octyl-phenyl ether (OP), a nonionic surfactant,was the emulsifier for the system. The experimental result indicates that TDI was reacted with DETA in a mass ratio of 3 to 1. FF-IR spectra confirm the formation of wall material, polyurea, from the two monomers, TDI and DETA.Encapsulation efficiency of n-eicosane is about 75%. Microcapsule of n-eicosane melts at a temperature close to that of n-eicosane, while its stored heat energy varies with core material n-eicosane when wall material fixed.Thermo-gravimetric analysis shows that core material n-eicosane, micro-n-eicosane and wall material polyurea can withstand temperatures up to 130, 170 and 250℃, respectively.     

Biofilms as bio-indicator for polluted waters?

The aim of this work was to investigate the heavy metal accumulation by natural biofilms living in the catchment area of the Tisza river in Hungary, as well as in biofilms cultivated in vitro. Laboratory tests have demonstrated that metals can be adsorbed on biofilms, depending on their concentration and on the availability of free sorptive places. Biofilms were cultivated in vitro in natural freshwater from the Saale river, Germany. After reaching the plateau phase, Cu was added to reach a concentration of 100 µg/L. An increase of its mass fraction in the biofilm was observed, which caused the decrease of the concentration in the water phase. Unfortunately, the reactor wall was also found to act as adsorbent for Cu. More detailed results of our in vitro experiments will be published in a forthcoming paper. Naturally grown biofilm samples from exposed as well as background places at the Hungarian rivers Szamos and Tisza were collected in 2000 and 2002 after the cyanide spill, and analysed using total reflection X-ray fluorescence analysis (TXRF). Metal mass fraction differences as high as two orders of magnitude were found between polluted and unpolluted (background) sampling points. Extremely high concentration values, e.g. 5600 µg/g Zn in biofilm, were found at highly polluted sampling points. This means an enrichment factor of ca. 10,000 compared to the water phase.     

Layered Double Hydroxide as Cordycepin Delivery Nanocarrier

Layered double hydroxides (LDHs), also called “anionic clays”, have received considerable attention due to their technological importance in catalysis, adsorption, optics, nanocomposite engineering materials and medical science1-5. LDHs are layered mate…