Zero Divisor Graphs of Finite Direct Products of Finite Rings

We determine the number of edges of the finite direct product of finite rings. We apply this result to finite rings without idempotents, in particular direct products of ? _m .     

A robust APTAS for the classical bin packing problem

Bin packing is a well studied problem which has many applications. In this paper we design a robust APTAS for the problem. The robust APTAS receives a single input item to be added to the packing at each step. It maintains an approximate solution throughout this process, by slightly adjusting the solution for each new item. At each step, the total size of items which may migrate between bins must be bounded by a constant factor times the size of the new item. We show that such a property cannot be maintained with respect to optimal solutions. A preliminary version of this paper appeared in Proceedings of the 33rd International Colloquium on Automata, Languages and Programming (ICALP2006), part I, pp. 214–225.     

Total synthesis of (+)-spiroindimicin A and congeners unveils their antiparasitic activity

The spiroindimicins are a unique class of chlorinated indole alkaloids characterized by three heteroaromatic rings structured around a congested spirocyclic stereocenter. Here, we report the first total synthesis of (+)-spiroindimicin A, which bears a challenging C-3′/C-5′′-linked spiroindolenine. We detail our initial efforts to effect a biomimetic oxidative spirocyclization from its proposed natural precursor, lynamicin D, and describe how these studies shaped our final abiotic 9-step solution to this complex alkaloid built around a key Pd-catalyzed asymmetric spirocyclization. Scalable access to spiroindimicins A, H, and their congeners has enabled discovery of their activity against several parasites relevant to human health, providing potential starting points for new therapeutics for the neglected tropical diseases leishmaniasis and African sleeping sickness.

Spiroindimicins A and H have been synthesized for the first time via a key palladium-catalyzed spirocyclization. Access to these alkaloids and several congeners has allowed the discovery of their antiparasitic properties.     

Identification of highly reactive sequences for PLP-mediated bioconjugation using a combinatorial peptide library

Chemical reactions that facilitate the attachment of synthetic groups to proteins are useful tools for the field of chemical biology and enable the incorporation of proteins into new materials. We have previously reported a pyridoxal 5'-phosphate (PLP)-mediated reaction that site-specifically oxidizes the N-terminal amine of a protein to afford a ketone. This unique functional group can then be used to attach a reagent of choice through oxime formation. Since its initial report, we have found that the N-terminal sequence of the protein can significantly influence the overall success of this strategy. To obtain short sequences that lead to optimal conversion levels, an efficient method for the evaluation of all possible N-terminal amino acid combinations was needed. This was achieved by developing a generalizable combinatorial peptide library screening platform suitable for the identification of sequences that display high levels of reactivity toward a desired bioconjugation reaction. In the context of N-terminal transamination, a highly reactive alanine-lysine motif emerged, which was confirmed to promote the modification of peptide substrates with PLP. This sequence was also tested on two protein substrates, leading to substantial increases in reactivity relative to their wild-type termini. This readily encodable tripeptide thus appears to provide a significant improvement in the reliability with which the PLP-mediated bioconjugation reaction can be used. This study also provides an important first example of how synthetic peptide libraries can accelerate the discovery and optimization of protein bioconjugation strategies.     

Synthesis and oxidation of d(6) tungsten pincer complexes: a complete series of tungsten(ii) hydridocarbonyl and halocarbonyl pincer complexes

Reaction of the neutral P(H)NP ligand [HN(SiMe(2)CH(2)PPh(2))(2)] with tungsten hexacarbonyl resulted in coordination of P(H)NP through both phosphorus donor atoms to form the tungsten complex [W(P(HN)P)(CO)(4)] (1). Reaction of P(H)NP with tris(acetonitrile)tricarbonyl tungsten gave both facial and meridional tridentate isomers [W(P(H)NP)(CO)(3)] (2-fac and 3-mer). These three d(6) tungsten complexes could be interconverted under appropriate conditions. The thermodynamically favored isomer 3 was protonated to form seven-coordinate [W(P(H)NP)(CO)(3)H][BF(4)] (4). A related series of cationic tungsten(ii) halide complexes was synthesized, [W(P(H)NP)(CO)(3)X](+) (6, X = I; 7, X = Br; 8, X = Cl; 9, X = F), by various routes. All of the tungsten(ii) complexes underwent deprotonation at the amine site of the P(H)NP ligand when triethylamine was added, resulting in neutral seven-coordinate complexes. Variable temperature (1)H, (31)P{(1)H}, and (13)C{(1)H} NMR spectroscopy showed fluxional behavior for all the seven-coordinate complexes reported here. Analysis of IR and NMR spectroscopic data showed trends through the series of coordinated halides. Crystal structures of tetracarbonyl 1, meridional tricarbonyl 3, and cationic hydride 4 were determined to confirm the coordination mode of the P(H)NP ligand.     

Validation of the Soleris E. coli method for detection and semi-quantitative determination of Escherichia coli in foods

The performance of the Soleris E. coli method was compared with that of the ISO 7251 most probable number (MPN) and detection reference methods for Escherichia coli. The Soleris E. coli method is a growth-based, rapid, automated system composed of temperature-controlled incubation chambers and photodiode-based optical detection devices for measurement of color changes in a prepared medium vial. A dilution of the test sample homogenate is inoculated directly into the vial. Products of E. coli metabolism alter the color of the medium over time, and this change is monitored by the Soleris instrument. The test is used in a dilute-to-specification or specification monitoring manner in which the result is positive or negative around a desired cutoff (in CFU/g) determined by the dilution and volume of sample homogenate added to the vial. Alternatively, the test is used for zero tolerance determinations (e.g., absence in 25 g) by performing an off-line pre-enrichment step followed by transfer of a portion of the pre-enrichment culture to the Soleris vial. Six E. coli strains originating from food sources were inoculated individually into six food commodities: frozen green beans, Echinacea powder, cocoa powder, sweetened condensed milk, pasteurized liquid egg, and shredded mozzarella cheese. Uninoculated samples were included in each trial. The results obtained by the ISO 7251 detection method and the Soleris E. coli method were shown to be in agreement by Chi-square analysis when the presence of E. coli was determined in 25 g of sample. Results from the Soleris E. coli dilute-to-specification method and the ISO 7251 MPN method were found to be in agreement by probability of detection statistical analysis. In inclusivity testing, 52 of 53 E. coli strains were detected within 24 h. Only a non-thermoduric strain of serotype O157:H43 was not detected. In exclusivity testing, all 31 strains tested produced negative results. Results of ruggedness experiments show that accurate results can be obtained even when the operating temperature of the Soleris instrument is set beyond normal tolerances. The internal and independent laboratory studies demonstrated that the Soleris E. coli method could be successfully utilized as an alternative to the reference methods, with a significant time savings of 2 to 3 days.     

Relationship between NMR shielding and heme binding strength for a series of 7-substituted quinolines

Chemical shielding tensors are calculated for the carbons in a series of 4-aminoquinolines with different substituents at the 7-position. The sigma(11) component is used as a measure of the relative pi-electron density at each carbon. By comparing the pi-electron density at each carbon with the log K of binding to heme (Kaschula et al. J. Med. Chem. 2002, 45, 3531), the drug-heme association is found to increase with increasing pi-electron density at the carbons meta to the substituent and with decreasing pi-electron density at the carbons ortho and para to the substituent. The greatest change in pi-electron density is at the ortho carbons, and log K increases with a decrease in pi-electron density on the ring containing the substituent, which corresponds to an increase in the pi-dipole between the two rings. An examination of the solution structures of the pi-pi complexes formed by amodiaquine and quinine with heme (Leed et al. Biochemistry 2002, 41, 10245. de Dios et al. Inorg. Chem. 2004, 43, 8078) shows that the pi-dipoles in each drug and in the porphyrin ring of heme may be paired. The chloro-substituted compound has an association constant that is an order of magnitude higher than the other compounds in the series, but the pi-electron density at the ring containing the substituent is not correspondingly low. This lack of correlation indicates that the Cl-substituted compound may be binding to heme in a manner that differs from the other compounds in the series.