Reuterin is an antimicrobial compound produced by Lactobacillus reuteri, and has been proposed to mediate, in part, the probiotic health benefits ascribed to this micro-organism. Despite 20 years of investigation, the mechanism of action by which reuterin exerts its antimicrobial effects has remained elusive. Here we provide evidence that reuterin induces oxidative stress in cells, most likely by modifying thiol groups in proteins and small molecules. Escherichia coli cells subjected to sublethal levels of reuterin expressed a set of genes that overlapped with the set of genes composing the OxyR regulon, which senses and responds to various forms of oxidative stress. E. coli cells mutated for oxyR were more sensitive to reuterin compared with wild-type cells, further supporting a role for reuterin in exerting oxidative stress. The addition of cysteine to E. coli or Clostridium difficile growth media prior to exposure to reuterin suppressed the antimicrobial effect of reuterin on these bacteria. Interestingly, interaction with E. coli stimulated reuterin production or secretion by L. reuteri, indicating that contact with other microbes in the gut increases reuterin output. Thus, reuterin inhibits bacterial growth by modifying thiol groups, which indicates that reuterin negatively affects a large number of cellular targets.

Catalytic asymmetric oxidations, most notably dihydroxylations, 1 epoxidations, 2-4 and aminohydroxylations, 5 have proven to be versatile transforms for the installation of chiral functionality onto non-chiral alkene substrates. In all three cases, the methodology has progressed and matured to the extent that the transformations are routinely applied in organic synthesis.Notably absent from this arsenal of transformations are examples of synthetically useful, conceptually related asymmetric electrophilic olefin halogenation reactions. With the intention of addressing this long-standing problem, we instituted a program geared towards the development of a reagent-controlled asymmetric halogenation of olefins.Recently, a polyene cascade induced by a stoichiometric chiral iodonium source was disclosed in an elegant work by Ishihara et al. 6a An efficient Co-salen catalyzed iodoetherification has also been reported by Kang et al. 6b Nonetheless, an efficient catalytic asymmetric halolactonization reaction has been elusive. In contrast to the number of examples of substrate controlled stereoselective halolactonizations, 7 reagent controlled processes are rare, and have only begun to emerge recently. The development of such a methodology would provide access to richly functionalized chiral halolactones in one step from achiral alkenoic acids.The first reagent controlled enantioselective halolactonization was reported in 1992 by the Taguchi group, where an alkenoic acid was cyclized by action of iodine and a stoichiometric equivalent of a chiral titanium complex, returning an iodolactone in 65% ee. 8 Subsequently, a number of examples have appeared that employ stoichiometric or super-stoichiometric amounts of chiral amine promoters. Typically, these methodologies employ a dimeric iodonium salt as the chiral halogen source (i.e. [(L*)2I+]Y-, where L* is a chiral amine). [8][9][10][11][12] Two of the most selective examples of this strategy were presented by Wirth 11,12 and Rousseau. 9 Aside from the disadvantage of committing up to ~5 equiv of chiral promoter, these approaches were marred by low enantioselectivities (15 to 45% ee). Interestingly, all of these disclosures produce iodolactones. Reports on chloro and bromolactonizations are absent, except for a single example where a bromolactone was produced in 5% ee with a chiral bromonium/pyridine dimer. 13 Recently, Gao and coworkers reported the only catalytic protocol for the iodolactonization of alkenoic acids, whereby trans-5-aryl-4-pentenoic acids were cyclized in the presence of iodine and 30 mol% of a cinchonidine-derived quaternary ammonium salt under PTC conditions. 14 Iodolactones were returned in a nearly 1:1 ratio of δ and γ isomers with marginal enantioselectivities (δ = 16% ee, γ = 31% ee).ak@chemistry.msu.edu . Supporting Information Available:. General experimental procedure for the chlorolactonization of alkenoic acids, and full spectroscopic data for each product. This material is available free of charge via the Internet at http://pubs.acs.org. W...

Environmental remediation relies mainly on using various technologies (e.g., adsorption, absorption, chemical reactions, photocatalysis, and filtration) for the removal of contaminants from different environmental media (e.g., soil, water, and air). The enhanced properties and effectiveness of nanotechnology-based materials makes them particularly suitable for such processes given that they have a high surface area-to-volume ratio, which often results in higher reactivity. This review provides an overview of three main categories of nanomaterials (inorganic, carbon-based, and polymeric-based materials) used for environmental remediation. The use of these nanomaterials for the remediation of different environmental contaminants—such as heavy metals, dyes, chlorinated organic compounds, organophosphorus compounds, volatile organic compounds, and halogenated herbicides—is reviewed. Various recent examples are extensively highlighted focusing on the materials and their applications.

Per-and polyfluoroalkyl substances (PFAS) are ubiquitous in many consumer products and present serious environmental challenges due to their persistent nature. Currently, conventional water treatment methods fail to remove PFAS, and other newly proposed materials/techniques face challenges when employed under realistic conditions. This study reports on poly(ethylenimine)-functionalized cellulose microcrystals (PEI-f-CMC) that showed a near-instant and high removal of PFAS under concentrations relevant to their actual occurrence in the natural environment (i.e., <1000 ng/L). The selective removal efficiency of 22 PFAS from different classes (i.e., legacy carboxylic and sulfonated PFAS, emerging carboxylic and sulfonated PFAS, and PFAS-precursors) using PEI-f-CMC was confirmed in lake water as well as solutions codosed with two additional types of natural organic matter. The performance of PEI-f-CMC was maintained in eight consecutive adsorption/regeneration cycles to remove PFAS. The PEI-f-CMC with its unique fast kinetics and high adsorption activity toward PFAS exhibits a great potential for being a promising alternative adsorbent for PFAS control.

Stereodefined carbon-halogen bonds are ubiquitous in nature with several natural products exhibiting this motif.[1] While the biogenetic origins of this unique chiral functionality has been a subject of several investigations in the past, [2] attempts by organic chemists to forge the carbon-halogen bond stereoselectively have largely been unsuccessful. This problem has come into focus only recently. Several elegant reports of asymmetric halogenations of alkenes and alkynes followed by an intramolecular attack of a pendant nucleophile have appeared in the literature in the last decade. Kang et al. reported a cobalt-salen catalyzed iodoetherification reaction.[3a] An asymmetric fluorocyclization of allyl silanes mediated by a cinchona alkaloid dimer was reported by Gouverneur and co-workers.[3b] Tang and co-workers disclosed an asymmetric bromolactonization of enynes catalyzed by a cinchona alkaloid derived urea; other bromolactonizations have also appeared following the disclosure of their report.[3c-e] More recently, Veitch and Jacobsen reported an asymmetric iodolactonization reaction mediated by chiral thiourea catalysts.[3f] Polyene cyclizations induced by chiral halonium ions have also been realized as reported by the research groups of Ishihara and Snyder.[4a-c] However, given the fledgling nature of this research area, one may find it easy to highlight the many drawbacks and limitations even in the present state of the art-for example, the relatively large catalyst loadings (superstoichiometric quantities in some cases) to achieve meaningful levels of enantioselectivity or the lack of a robust catalytic system that can catalyze a number of diverse reactions rather than one specific reaction. Moreover, efficient asymmetric chlorocyclizations have remained underdeveloped. This situation is attributable, at least in part, to the highly reactive nature of chloronium ions, which are known to exist in equilibrium with the corresponding carbocation rather than exclusively as cyclic chloronium ions, [5a-c] thus making the development of chlorocyclizations a formidable challenge.Our research group has recently reported the catalytic asymmetric chlorolactonization of alkenoic acids.[7] Herein, we disclose the efficient halocyclization of unsaturated amides to furnish chiral heterocycles. Furthermore, these heterocycles have been transformed into useful chiral building blocks such as amino alcohols.Chiral heterocycles such as oxazolines and dihydrooxazines are commonly encountered motifs in natural products, [8a] molecules of pharmaceutical interest, [8b] and in several chiral ligands.[8c] Their syntheses, however, usually employ stoichiometric quantities of chiral amino alcohols. With only one precedented method to access these molecules in a catalytic asymmetric fashion, [6] we were intrigued by the possibility of one-step access to these versatile chiral heterocycles by a catalytic asymmetric halocyclization of easily accessed unsaturated amides.We chose the conversion of benzamide 1 into oxazoline 2 as our init...

N-Acylated N-chlorohydantoins are shown to be competent chlorenium sources in the (DHQD)(2)PHAL-mediated asymmetric chlorolactonization. The derivatives demonstrate the exact role of the N1 and N3 chlorine atoms in the parent dichlorohydantoins with the N1 chlorine serving as an inductive activator and the N3 chlorine being delivered to the substrate. The putative associated catalyst/chlorine source complex was experimentally demonstrated through a series of matched/mismatched experiments employing chiral N-chlorinated hydantoins.

Heme, an iron-containing organic ring, is essential for virtually all living organisms by serving as a prosthetic group in proteins that function in diverse cellular activities ranging from diatomic gas transport and sensing, to mitochondrial respiration, to detoxification. Cellular heme levels in microbial pathogens can be a composite of endogenous de novo synthesis or exogenous uptake of heme or heme synthesis intermediates. Intracellular pathogenic microbes switch routes for heme supply when heme availability fluctuates in their replicative environment throughout infection. Here, we show that Toxoplasma gondii, an obligate intracellular human pathogen, encodes a functional heme biosynthesis pathway. A chloroplastderived organelle, termed apicoplast, is involved in heme production. Genetic and chemical manipulation revealed that de novo heme production is essential for T. gondii intracellular growth and pathogenesis. Surprisingly, the herbicide oxadiazon significantly impaired Toxoplasma growth, consistent with phylogenetic analyses that show T. gondii protoporphyrinogen oxidase is more closely related to plants than mammals. This inhibition can be enhanced by 15-to 25-fold with two oxadiazon derivatives, lending therapeutic proof that Toxoplasma heme biosynthesis is a druggable target. As T. gondii has been used to model other apicomplexan parasites, our study underscores the utility of targeting heme biosynthesis in other pathogenic apicomplexans, such as Plasmodium spp., Cystoisospora, Eimeria, Neospora, and Sarcocystis.

The generic position of a gram-positive, facultatively methylotrophic actinomycete known as Nocardiu sp. strain 239 was determined by comparing reverse transcriptase sequences of 16s rRNA. The assignment of the organism to the genus Amycolatopsis was strongly supported by chemotaxonomic and morphological data. A comparison with the type strains of validly described Amycolatopsis species showed that the organism formed the nucleus of a new species. The name proposed for this new species is Amycolatopsis methanolica. The organism has been deposited in the National Collection of Industrial Bacteria as NCIB 11946.Methanol-utilizing bacteria that assimilate formaldehyde via the ribulose monophosphate cycle (1, 42) are potential vehicles for fermentative overproduction of aromatic amino acids (7,38,40). The precursors of the shikimate pathway in these strains, namely, erythrose-4-phosphate and phosphoenolpyruvate, are intermediate and end products, respectively, of the ribulose monophosphate cycle. Gram-negative ribulose monophosphate cycle bacteria are not amenable to the extensive physiological and genetical manipulations needed for strain development in view of their obligate methylotrophic nature (26). There is, however, evidence that gram-positive, facultatively methylotrophic bacteria (6, 8) are suitable for strain improvement studies (4, 35).The single gram-positive ribulose monophosphate cycle actinomycete already described was initially labeled Streptomyces sp. strain 239 (29-31) and then Nocardia sp. strain 239 (24). Stable mutants have been isolated from this metabolically versatile organism, which has been grown under diverse conditions in batch and continuous cultures (4, 24). Regulation of aromatic amino acid biosynthesis in the strain has been studied in detail (9, and examination of the systematic deregulation of these control systems and the development of a transformation system are under way. Preliminary chemosy stematic studies included in this report showed that Nocardia sp. strain 239 has chemical properties consistent with its assignment of the family Pseudonocardiaceae (ll), which encompasses the genera Actinopolyspora, Amycolatopsis, Faenia, Pseudonocardia, Saccharomonospora, Saccharopolyspora, and in all probability, Amycolata (T. Bowen, E . Stackebrandt, M. Dorsch, and M. Embley, J. Gen. Microbiol., in press). In the present investigation, Nocardia sp. strain 239 was further characterized and designated the type strain of Amycolatopsis methanolica sp.nov . MATERIALS AND METHODSTest strains and cultivation conditions. Nocardia sp. strain 239 (strain LMD 80.32