Unexpected ring transformation to pyrrolo[3.2-b]pyridine derivatives. Fused azolium salts. 22

2-Arylsulfanyl and 2-benzylsulfanylpyridinium N-arylimides (2) easily prepared from 3-aryltetrazolopyridinium salts (1) with aryl and benzylthiolates, respectively, reacted with various dipolarophiles yielding cycloadducts that underwent transformation to give tetrahydropyrrolo[3,2-b]pyridines (5, 6, and 8) in good yields. A similar rearrangement (formation of 15) was also observed in the case of parent derivatives being unsubstituted in position 2 (12). The abscence of any significant solvent effect, comparison of the sulfur and non-sulfur analogues, as well as the stereoselective nature of the observed ring transformation seem to support a sigmatropic mechanism. Structure elucidation of the products has been carried out by single-crystal X-ray diffraction and (1)H NMR experiments.     

Synthesis of the dibenzo[f,h]phthalazine and dibenzo[f,h]cinnoline skeleton via a ‘Suzuki-Pd-catalyzed intramolecular arylation’ and a ‘Suzuki-Pschorr’ approach

Palladium-catalyzed intramolecular arylation of 2-benzyl-5-(2-bromophenyl)-4-phenylpyridazin-3(2H)-one yielded hitherto unknown 2-benzyldibenzo[f,h]phthalazin-1(2H)-one. The synthesis of this new tetracyclic pyridazinone from 2-benzyl-5-(2-aminophenyl)-4-phenylpyridazin-3(2H)-one via a Pschorr type reaction was also investigated. Similarly, the construction of 2-methyldibenzo[f,h]cinnolin-3(2H)-one from 2-methyl-5-(2-bromophenyl)-6-phenylpyridazin-3(2H)-one and 2-methyl-5-(2-aminophenyl)-6-phenylpyridazin-3(2H)-one is also reported. Removal of the N-benzyl protective group of 2-benzyl-dibenzo[f,h]phthalazin-1(2H)-one with AlCl₃ yielded unsubstituted dibenzo[f,h]phthalazin-1(2H)-one.     

Noncovalent cross-links in context with other structural and functional elements of proteins

Proteins are heteropolymers with evolutionary selected native sequences of residues. These native sequences code for unique and stable 3D structures indispensable for biochemical activity and for proteolysis resistance, the latter which guarantees an appropriate lifetime for the protein in the protease rich cellular environment. Cross-links between residues close in space but far in the primary structure are required to maintain the folded structure of proteins. Some of these cross-links are covalent, most frequently disulfide bonds, but the majority of the cross-links are sets of cooperative noncovalent long-range interactions. In this paper we focus on special clusters of noncovalent long-range interactions: the Stabilization Centers (SCs). The relation between the SCs and secondary structural elements as well as the relation between SCs and functionally important regions of proteins are presented to show a detailed picture of these clusters, which are believed to be primarily responsible for major aspects of protein stability.     

Synthesis of Vinca Alkaloids and Related Compounds. LXV. Preparation of 7-Methoxytryptamine

7-Methoxytryptamine (6a) was prepared from cheap and easily available starting materials by using the Abramovitch-Shapiro method.     

Trace level triacetone-triperoxide identification with SPME–GC-MS in model systems

Triacetone-triperoxide is a high explosive mainly used by terrorist groups. With the spreading of the recipe on the Internet, increasing number of bomb attacks are being reported worldwide using triacetone-triperoxide. A simple identification method is described using 100 μm polydimethyl siloxane fibre solid phase microextraction and gas chromatography combined with spectrometry. The method was tested on various pre- and post-explosion models that can be collected in a house search or after a bomb attack. Sample preservation and stability was also examined. Identification of triacetone-triperoxide residues in post-explosion models was feasible 24 h after ignition, the detection limit being 5 ng.     

Design of online solid phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) hyphenated systems for quantitative analysis of small organic compounds in biological matrices

Three online solid phase extraction-liquid chromatography-tandem mass spectrometry (SPE-LC-MS/MS) method examples are presented where two different types of chromatographic columns or solvent systems were coupled to meet specific analytical objectives: (i) SPE of target analytes by restricted access media from high ionic strength urine matrix was coupled with reversed phase LC-MS/MS conditions accommodating high ionization potentials of the analytes (urinary bisphenol A and other phenolic derivatives); (ii) strong cation exchange SPE of analytes of diverse polarity and pK(a) was coupled with reversed phase LC-MS/MS analysis (urinary atrazine metabolites); (iii) pre-concentration of low pg per sample analytes by weak anion exchange SPE was hyphenated with ion pair LC-MS analysis (intracellular nucleotide triphosphate analogs). With these examples we suggest a conductive generic work flow for the development of online SPE-LC-MS methods and show how advanced commercial LC devices and software allow for the design of complex yet highly versatile analytical separation systems suited to the unique physicochemical properties of the target analytes.     

In vitro study of antibiotic effect on bacterial adherence to acrylic intraocular lenses

Implantation of artificial intraocular lenses into the eye during ophthalmic surgical procedures ensures an unliving surface on which bacterial pathogens may attach and form biofilms. Despite antibiotic treatment bacteria growing in biofilms might cause inflammation and serious complications. In this study the adhesive ability of 7 Staphylococcus aureus and 11 coagulase-negative Staphylococcus (CNS) strains to the surface of acrylic intraocular lenses had been examined by the ultrasonic method. In untreated cases adhesion of the S. aureus and CNS strains did not differ significantly. We could not demonstrate significant differences between the adhesive ability of the standard strains and the clinical isolates. In this study a single – 60 min long – antibiotic (ciprofloxacin and tobramycin) treatment had been applied, that correlate well with the single or intermittant antibiotic prophylaxis of patients. Ciprofloxacin administration was able to reduce significantly the number of attached cells on the surface of acrylic lenses both in the case of S. aureus and CNS strains. Dependence of the effect from concentration could also be demonstrated. Tobramycin treatment was able to inhibit significantly the attachment of S. aureus cells. Despite the debate on antibiotic prophylaxis we presented in our experiments that a single antibiotic administration can decrease the attachment of bacterial cells to the surface of acrylic intraocular lenses, and might be effective in the prevention of postoperative endophthalmitis, that is a rare but serious complication of ophthalmic surgery.