Synthesis and Structure Investigations of Potential Sedative and Anticonvulsant Hydroxy- and Acetoxy-N-(3-oxobutyl)-pyrido[2,3-d]pyridazinonesa

Summary.  Novel N-(3-oxobutyl)-hydroxy- and acetoxypyrido[2,3-d]pyridazinones were synthesized and tested in vivo for their sedative and anticonvulsant activity. The Michael-type reaction of quinolinic acid hydrazide and methyl vinyl ketone afforded a mixture of two isomers, 5-hydroxy-N ⁷-(3-oxobutyl)-pyrido[2,3-d]pyridazin-8(7H)-one and 8-hydroxy-N ⁶-(3-oxobutyl)-pyrido[2,3,-d]pyridazin-5-(6H)-one, in a ratio of 2:1 which were separated by crystallization. Subsequent acetylation of both isomers yielded the corresponding 5- and 8-acetoxy compounds. The structures of the compounds were proven and completely assigned on the basis of ¹H, ¹³C, ¹⁵N NMR, and 1D NOE difference spectra as well as 2D C,H-correlation experiments. Preliminary pharmacological tests showed low acute toxicity with a LD ₅₀ > 1000 mg/kg in the mouse and sedative activity for the title compounds. 5-Acetoxy-N ⁷- (3-oxobutyl)-pyrido[2,3-d]pyridazin-8(7H)-one displayed a borderline anticonvulsant activity in the metrazole test model. Corresponding author. E-mail: edith.goessnitzer@uni-graz.at Received March 20, 2002; accepted April 3, 2002     

Channel activity of a viral transmembrane peptide in micro-BLMs: Vpu(1-32) from HIV-1

We report for the first time on pore-suspending lipid bilayers, which we call micro-black lipid membranes (micro-BLMs), based on a highly ordered macroporous silicon array. Micro-BLMs were established by first functionalizing the backside porous silicon surface with gold and then chemisorbing 1,2-dipalmitoyl-sn-glycero-3-phosphothioethanol followed by spreading 1,2-diphytanoyl-sn-glycero-3-phosphocholine dissolved in n-decane. Impedance spectroscopy revealed the formation of single lipid bilayers confirmed by a mean specific capacitance of 0.6 +/- 0.2 microF/cm2. Membrane resistances were in the G omega-regime and beyond. The potential of the system for single channel recordings was demonstrated by inserting the transmembrane domain of the HIV-1 accessory peptide Vpu(1-32), which forms helix bundles with characteristic opening states. We elucidated different amilorides as potential drugs to inhibit channel activity of Vpu.     

Design magnetischer Materialien: Chemie der Magnete

The field of molecular based magnetism is an active area of research directed toward the design of new magnetic materials. The idea is to introduce molecular strategies in magneto-chemistry. This can open completely new synthetic routes to materials with previously unknown physical properties. Spin carriers used within this approach range from purely organic radicals to metal complexes and organometallic compounds. The design of new magnetic materials with tailor-made properties requires a detailed knowledge about the interactions between possible spin carriers and the strategies necessary to achieve interactions in all three dimensions. The latter is closely related to the field of crystal engineering. Starting from introductory remarks to magnetochemistry the underlaying concepts for the design of magnetic materials on the basis of molecular compounds as well as new developments and possible applications are described.     

Synthesis,Reactivity, and Structural Characterization of Dioxovanadium(V) Complexes with Tridentate Schiff Base Ligand: Vanadium Complexes in Supramolecular Networks

The synthesis, characterization and crystal structure analysis of the ammonium salt of the dioxovanadium(V) complex NH₄[VO₂(salhyph)] with the tridentate Schiff base ligand derived from salicylaldehyde and benzoic acid hydrazide (H₂salhyph) is reported. NH₄[VO₂(salhyph)] crystallizes in the monoclinic space group Pn with a = 708.8(2), b = 1444.3(3), c = 717.1(2) pm and β = 101.09(2)°. The vanadium atom of the dioxovanadium(V) moiety has a distorted square‐pyramidal coordination geometry. Extensive hydrogen bonding is observed between the ammonium cation and the oxygen atoms coordinated to the vanadium atom yielding to a two‐dimensional network, where the complex anions are arranged in a bilayer. Additional crystal packing within the bilayer appears to be controlled mostly by π stacking between the aromatic rings of the ligand. The reactions of NH₄[VO₂(salhyph)] with several proton acidic compounds including water, methanol, and proton acids lead to neutral monooxovanadium(V) and dioxovanadium(V) complexes ([VO₂(Hsalhyph)], [V₂O₃(salhyph)₂] and [VO(OMe)(salhyph)(HOMe)]).     

Enzymatic Conversion of Flavonoids using Bacterial Chalcone Isomerase and Enoate Reductase

Flavonoids are a large group of plant secondary metabolites with a variety of biological properties and are therefore of interest to many scientists, as they can lead to industrially interesting intermediates. The anaerobic gut bacterium Eubacterium ramulus can catabolize flavonoids, but until now, the pathway has not been experimentally confirmed. In the present work, a chalcone isomerase (CHI) and an enoate reductase (ERED) could be identified through whole genome sequencing and gene motif search. These two enzymes were successfully cloned and expressed in Escherichia coli in their active form, even under aerobic conditions. The catabolic pathway of E. ramulus was confirmed by biotransformations of flavanones into dihydrochalcones. The engineered E. coli strain that expresses both enzymes was used for the conversion of several flavanones, underlining the applicability of this biocatalytic cascade reaction.     

Chiral tetranuclear mu3-alkoxo-bridged copper(II) complex with 2 + 4 cubane-like Cu4O4 core framework and ferromagnetic ground state

The sugar-modified Schiff base ligand benzyl 2-deoxy-2-salicylideneamino-alpha-D-glucopyranoside H 2L, prepared by condensation of salicylaldehyde and the monomeric chitosan analogue benzyl 2-deoxy-2-amino-alpha-D-glucopyranoside, reacts with copper(II) acetate to form a self-assembled, alkoxo-bridged tetranuclear homoleptic copper(II) complex [{Cu(L)}4] (4) with Cu4O4 heterocubane core. The chiral complex 4 crystallizes in the space group P2 12 12 1. The tetranuclear complex 4 is composed of two dinuclear {Cu(L)}2 entities linked by the four mu 3-bridging C-3 alkoxide oxygen atoms of the sugar backbone. The preorganization of the dimeric {Cu(L)}2 entities is enforced by strong hydrogen bonds between the phenolate oxygen atom and the C-4 hydroxy group of the two constituting chiral monomeric building blocks. Therefore the Cu4O4 core can be classified as a type I or 2 + 4 cubane. The chirality of the structure is confirmed by circular dichroism (CD) spectra, which reveal a significant dichroism associated with the copper centered transitions at around 600 nm. Temperature dependent magnetic susceptibility measurements indicate ferromagnetic exchange interactions in complex 4. Fitting of the experimental data with a two J model based on the 2 + 4 topology ( H = - J1(S1S3 + S2S4) - J2(S1 + S3)(S2 + S4)) leads to exchange coupling constants of J1 = 64 and J2 = 4 cm(-1). The observed ferromagnetic coupling can be attributed to the very small Cu-O-Cu bridging angles within the Cu2O2 core of the constituting dimeric entities, which are a result of the conformational requirements introduced by the sugar backbone. 4 is not only the first example of an alkoxo-bridged tetranuclear copper(II) complex with Cu4O4 core representing the 2 + 4 cubane class with ferromagnetic ground state but also a rare example for the class of molecules combining a ferromagnetic ground state with optical activity. The ferromagnetic S = 2 ground state of 4 is confirmed by magnetization measurements and ESR spectroscopy.     

Non-destructive bulk analysis of the Buggenum sword by neutron resonance capture analysis and neutron diffraction

Two neutron based techniques, neutron resonance capture analysis (NRCA) and time-of-flight neutron-diffraction (TOF-ND) have been used to determine the elemental composition and structure of a precious and very well preserved all-metal sword from the Bronze Age. This Buggenum sword was on loan from the National Museum of Antiquities (NMA) in Leiden (NL). NRCA and TOF-ND experiments have been carried out at a number of more or less identical positions of the sword. The tin-bronze ratio and the relative amounts of some minor elements (Sb, As, Ag, In) have been determined. The results of neutron diffraction measurements showed considerable tin-segregation, and clear indications of hardening on the edges of the blade. In addition, radiographs using Bremsstrahlung revealed the construction of the hilt–blade connection. The work was carried out at the EC Joint Research Centre IRMM in Geel (B) and at the ISIS facility of the Rutherford Appleton Laboratory (UK).     

Efficient electron transfer through a triazole link in ruthenium(II) polypyridine type complexes

Spectroscopic, electrochemical and theoretical characterisations of photoactive systems readily assembled via click-chemistry show an efficient bi-directional charge shift through the triazole link.