Chemistry of thienopyridines. XXXIII. Synthetic routes to 5- and 7-substituted thieno[3,2-b]pyridines from the N-oxide

Thieno[3,2-b]pyridine ( 1 ) is oxidized to N-oxide 1a by means of m-chloroperoxybenzoic acid (83%). Compound 1a forms adducts with hydrogen chloride and picric acid and gives ring substitution alpha or gamma to the heteronitrogen atom. Thus, 1a plus nitric and sulfuric acids produces the 7-nitro-N-oxide 1m (63%), or plus phosphorus oxychloride gives a mixture of 5-chloro and 7-chloro ( 1j ) derivatives of 1 . Compound 1m is convertible into a variety of other derivatives of 1 , viz. 7-chloro-N-oxide, 1j , 7-bromo-N-oxide, 7-nitro and 7-amino. 5-Cyano- 1 , formed from 1a , is, in turn, transformed into a methyl imidate (93%), cyclic amidines, and a 5-tetrazolyl- 1 (91%). These results confirm the prediction that 1a , thieno[2,3-b]pyridine-4-oxide and quinoline 1-oxide should exhibit closely similar (i.e. analogous) chemical reactions.     

Large antichains in the partition lattice

Consider the partially ordered set of all partitions of an n-element set, ordered by refinement. The sizes of the various ranks within this poset are the Stirling numbers of the second kind. We show that the ratio of the size of the largest antichain to the size of the largest rank exceeds n^1/35 for all n sufficiently large.     

Co-H-maps to spheres

Criteria are given which characterize Co-H and Co-A maps from arbitrary double suspensions to odd dimensional spheres in terms of the maps in the EHP sequence.     

Conformational changes in a photosensory LOV domain monitored by time-resolved NMR spectroscopy

Phototropins are light-activated kinases from plants that utilize light-oxygen-voltage (LOV) domains as blue light photosensors. Illumination of these domains leads to the formation of a covalent linkage between the protein and an internally bound flavin chromophore, destabilizing the surrounding protein and displacing an alpha-helix from its surface. Here we use a combination of spectroscopic tools to monitor the kinetic processes that spontaneously occur in the dark as the protein returns to the noncovalent ground state. Using time-resolved two-dimensional (2D) NMR methods, we measured the rate of this process at over 100 independent sites throughout the protein, establishing that regeneration of the dark state occurs cooperatively within a 1.6-fold range of observed rates. These data agree with other spectroscopic measurements of the kinetics of protein/FMN bond cleavage and global conformational changes, consistent with these processes experiencing a common rate-limiting step. Arrhenius analyses of the temperature dependence of these rates suggest that the transition state visited during this regeneration has higher energy than the denatured form of this protein domain despite the fact that there is no global unfolding of the domain during this process.     

The synthesis of some bidentate ligands containing both phosphine and nitrile groups

Both (C₆H₅)₂P(CH₂)₃CN and (C₆H₅)₂P(CH₂)₄CN have been obtained from the reaction of Br(CH₂)_nCN (n = 3, 4) with (C₆H₅)₂POCH₃ followed by reduction with (C₆H₅)₂SiH₂. These phosphine-nitrile ligands form L₂PdCl₂ complexes which are shown by IR measurements to have trans geometries with the phosphine portions of the ligands coordinated. Reactions of o-BrC₆H₄CN with CH₃(CH₂)₃Li followed by R₂PCl (R = C₆H₅ or (CH₃)₂N) have been used to provide good yields of the corresponding R₂P-o-C₆H₄CN products.     

Laboratory and field experiments used to identify<Emphasis Type="Italic"> Canis lupus</Emphasis> var. <Emphasis Type="Italic">familiaris</Emphasis> active odor signature chemicals from drugs,explosives, and humans

This paper describes the use of headspace solid-phase microextraction (SPME) combined with gas chromatography to identify the signature odors that law enforcement-certified detector dogs alert to when searching for drugs, explosives, and humans. Background information is provided on the many types of detector dog available and specific samples highlighted in this paper are the drugs cocaine and 3,4-methylenedioxy-N-methylamphetamine (MDMA or Ecstasy), the explosives TNT and C4, and human remains. Studies include the analysis and identification of the headspace "fingerprint" of a variety of samples, followed by completion of double-blind dog trials of the individual components in an attempt to isolate and understand the target compounds that dogs alert to. SPME–GC/MS has been demonstrated to have a unique capability for the extraction of volatiles from the headspace of forensic specimens including drugs and explosives and shows great potential to aid in the investigation and understanding of the complicated process of canine odor detection. Major variables evaluated for the headspace SPME included fiber chemistry and a variety of sampling times ranging from several hours to several seconds and the resultant effect on ratios of isolated volatile components. For the drug odor studies, the CW/DVB and PDMS SPME fibers proved to be the optimal fiber types. For explosives, the results demonstrated that the best fibers in field and laboratory applications were PDMS and CW/DVB, respectively. Gas chromatography with electron capture detector (GC/ECD) and mass spectrometry (GC/MS) was better for analysis of nitromethane and TNT odors, and C-4 odors, respectively. Field studies with detector dogs have demonstrated possible candidates for new pseudo scents as well as the potential use of controlled permeation devices as non-hazardous training aids providing consistent permeation of target odors.     

Controlled composting of straw

Production of composts on the farm from surplus straw might provide a low-cost biotechnological approach for increasing the value of this lignocellulosic waste. Successful composting depends on the conversion of the polysaccharides (cellulose and hemicelluloses) of straw by inoculated microorganisms to products that can promote plant growth when applied to the land. None of the potentially useful products we have identified are produced by cellulolytic organisms. We have therefore studied mixed populations in which noncellulolytic bacteria depend for growth on the products of fungal cellulolysis. The nature and yield of bacterial products depends not only on conditions within the compost, but also on the microbial inoculants used. Under defined laboratory conditions, using pure cellulose, N₂ is fixed by the anaerobic bacteriumClostridium butyricum in association with a cellulolytic fungus such asTrichoderma sp. A similar association has been achieved on straw withPenicillium corylophilum as the cellulolytic fungus. Cellulolytic fungi can also provide available substrates for the production of bacterial polysaccharides that can improve the structure of unstable soils. The yield of polysaccharide and its efficacy in soil aggregate stabilization again varies with the inoculants used. Such composts can thus contribute to plant nutrition and to soil structure. The adoption ofTrichoderma spp. as the cellulolytic inoculants would further extend the potential value of the compost to include the biocontrol of plant pathogens.     

meso-Indanyl calix[4]pyrrole receptors

Two new meso-indanyl-substituted calix[4]pyrrole receptors, 2 and 3, have been synthesized. A range of calix[4]pyrrole host-neutral molecule complexes crystallise from solutions of 2 in a variety of solvents and the structures of four have been elucidated by X-ray crystallography. The F⁻ and Cl⁻ anion affinities of 2 have been measured in acetonitrile, and are significantly different from the corresponding affinities of the prototypical calix[4]pyrrole, the octamethyl-derivative, 1. ESI-FTICR-MS has been used to determine the relative F⁻ and Cl⁻ anion affinities of receptors 1 and 2 in methanol-acetonitrile solution. Deprotonation of 1 and 2 by fluoride is observed (under the conditions of the MS experiment).     

Electroaddressable Selective Functionalization of Electrode Arrays: Catalytic NADH Detection Using Aryl Diazonium Modified Gold Electrodes

We report the application of 4‐nitrophenyl diazonium modified electrodes towards the electrochemical detection of NADH. Selective activation of individual electrodes on a 5 element array by electro‐addressable conversion of nitro groups to amines and subsequent EDC/NHS crosslinking to the NADH oxidant, pyrroloquinoline quinone (PQQ), is demonstrated. Inactivated electrodes retained nitro functionality and were protected against non‐specific adsorption and mild chemical reactions. Electrodeposition conditions were used to control nitrophenyl film thickness and showed that while increased film thickness leads to greater functionalization density of PQQ, it also results in decreased electron transfer kinetics. The electrodeposition protocol can therefore serve as a method to control electrode functionalization density and film electron transfer kinetics. We believe this simple technique for selective electrode functionalization may facilitate the development of next generation multianalyte electrochemical sensors.