Multistep Solid-State Organic Synthesis of Carbamate-Linked Covalent Organic Frameworks.

Herein, we demonstrate the first example of a multistep solid-state organic synthesis, in which a new imine-linked two-dimensional covalent organic framework (COF-170, 1) was transformed through three consecutive postsynthetic modifications into porous, crystalline cyclic carbamate and thiocarbamate-linked frameworks. These linkages are previously unreported and inaccessible through de novo synthesis. While not altering the overall connectivity of the framework, these chemical transformations induce significant conformational and structural changes at each step, highlighting the key importance of noncovalent interactions and conformational flexibility to COF crystallinity and porosity. These transformations were assessed using 15N multiCP-MAS NMR spectroscopy, providing the first quantitation of yields in COF postsynthetic modification reactions, as well as of amine defect sites in imine-linked COFs. This multistep COF linkage postsynthetic modification represents a significant step toward bringing the precision of organic solution-phase synthesis to extended solid-state compounds.

Local Electronic Structure of Molecular Heterojunctions in a Single-Layer 2D Covalent Organic Framework.

The synthesis of a single-layer covalent organic framework (COF) with spatially modulated internal potentials provides new opportunities for manipulating the electronic structure of molecularly defined materials. Here, the fabrication and electronic characterization of COF-420: a single-layer porphyrin-based square-lattice COF containing a periodic array of oriented, type II electronic heterojunctions is reported. In contrast to previous donor-acceptor COFs, COF-420 is constructed from building blocks that yield identical cores upon reticulation, but that are bridged by electrically asymmetric linkers supporting oriented electronic dipoles. Scanning tunneling spectroscopy reveals staggered gap (type II) band alignment between adjacent molecular cores in COF-420, in agreement with first-principles calculations. Hirshfeld charge analysis indicates that dipole fields from oriented imine linkages within COF-420 are the main cause of the staggered electronic structure in this square grid of atomically-precise heterojunctions.

Conversion of Imine to Oxazole and Thiazole Linkages in Covalent Organic Frameworks.

Imine-linked ILCOF-1 based on 1,4-phenylenediamine and 1,3,6,8-tetrakis(4-formylphenyl)pyrene was converted through consecutive linker substitution and oxidative cyclization to two isostructural covalent organic frameworks (COFs), having thiazole and oxazole linkages. The completeness of the conversion was assessed by infrared and solid-state NMR spectroscopies, and the crystallinity of the COFs was confirmed by powder X-ray diffraction. Furthermore, the azole-linked COFs remain porous, as shown by nitrogen sorption experiments. The materials derived in this way demonstrate increased chemical stability, relative to the imine-linked starting material. This constitutes a facile method for accessing COFs and linkages that are otherwise difficult to crystallize due to their inherently limited microscopic reversibility.

Practical water production from desert air.

Energy-efficient production of water from desert air has not been developed. A proof-of-concept device for harvesting water at low relative humidity was reported; however, it used external cooling and was not desert-tested. We report a laboratory-to-desert experiment where a prototype using up to 1.2 kg of metal-organic framework (MOF)-801 was tested in the laboratory and later in the desert of Arizona, USA. It produced 100 g of water per kilogram of MOF-801 per day-and-night cycle, using only natural cooling and ambient sunlight as a source of energy. We also report an aluminum-based MOF-303, which delivers more than twice the amount of water. The desert experiment uncovered key parameters pertaining to the energy, material, and air requirements for efficient production of water from desert air, even at a subzero dew point.

Palladium-catalysed anti-Markovnikov selective oxidative amination.

In recent years, the synthesis of amines and other nitrogen-containing motifs has been a major area of research in organic chemistry because they are widely represented in biologically active molecules. Current strategies rely on a multistep approach and require one reactant to be activated prior to the carbon-nitrogen bond formation. This leads to a reaction inefficiency and functional group intolerance. As such, a general approach to the synthesis of nitrogen-containing compounds from readily available and benign starting materials is highly desirable. Here we present a palladium-catalysed oxidative amination reaction in which the addition of the nitrogen occurs at the less-substituted carbon of a double bond, in what is known as anti-Markovnikov selectivity. Alkenes are shown to react with imides in the presence of a palladate catalyst to generate the terminal imide through trans-aminopalladation. Subsequently, olefin isomerization occurs to afford the thermodynamically favoured products. Both the scope of the transformation and mechanistic investigations are reported.

Chemical Conversion of Linkages in Covalent Organic Frameworks.

The imine linkages of two layered, porous covalent organic frameworks (COFs), TPB-TP-COF ([C6H3(C6H4N)3]2[C6H4(CH)2]3, 1) and 4PE-1P-COF ([C2(C6H4N)4][C6H4(CH)2]2, 2), have been transformed into amide linkages to make the respective isostructural amide COFs 1' and 2' by direct oxidation with retention of crystallinity and permanent porosity. Remarkably, the oxidation of both imine COFs is complete, as assessed by FT-IR and 13C CP-MAS NMR spectroscopy and demonstrates (a) the first chemical conversion of a COF linkage and (b) how the usual "crystallization problem" encountered in COF chemistry can be bypassed to access COFs, such as these amides, that are typically thought to be difficult to obtain by the usual de novo methods. The amide COFs show improved chemical stability relative to their imine progenitors.

Chemistry of Covalent Organic Frameworks.

Linking organic molecules by covalent bonds into extended solids typically generates amorphous, disordered materials. The ability to develop strategies for obtaining crystals of such solids is of interest because it opens the way for precise control of the geometry and functionality of the extended structure, and the stereochemical orientation of its constituents. Covalent organic frameworks (COFs) are a new class of porous covalent organic structures whose backbone is composed entirely of light elements (B, C, N, O, Si) that represent a successful demonstration of how crystalline materials of covalent solids can be achieved. COFs are made by combination of organic building units covalently linked into extended structures to make crystalline materials. The attainment of crystals is done by several techniques in which a balance is struck between the thermodynamic reversibility of the linking reactions and their kinetics. This success has led to the expansion of COF materials to include organic units linked by these strong covalent bonds: B-O, C-N, B-N, and B-O-Si. Since the organic constituents of COFs, when linked, do not undergo significant change in their overall geometry, it has been possible to predict the structures of the resulting COFs, and this advantage has facilitated their characterization using powder X-ray diffraction (PXRD) techniques. It has also allowed for the synthesis of COF structures by design and for their formation with the desired composition, pore size, and aperture. In practice, the modeled PXRD pattern for a given expected COF is compared with the experimental one, and depending on the quality of the match, this is used as a starting point for solving and then refining the crystal structure of the target COF. These characteristics make COFs an attractive class of new porous materials. Accordingly, they have been used as gas storage materials for energy applications, solid supports for catalysis, and optoelectronic devices. A large and growing library of linkers amenable to the synthesis of COFs is now available, and new COFs and topologies made by reticular synthesis are being reported. Much research is also directed toward the development of new methods of linking organic building units to generate other crystalline COFs. These efforts promise not only new COF chemistry and materials, but also the chance to extend the precision of molecular covalent chemistry to extended solids.

Nickel-Mediated Synthesis of Isoindolinones at Room Temperature.

This communication describes a method for the Ni(cod) 2-mediated intramolecular arylation of alkyl C-H bonds adjacent to the nitrogen atom in benzamide substrates. The transformation proceeds at room temperature and exhibits selectivity for functionalization of more substituted C-H bonds. The yields of the desired isoindolinone products are higher with benzamide substrates containing tertiary alkyl groups on the nitrogen atom than with those bearing primary or secondary alkyls. The results described herein suggest a mechanism involving radical intermediates for these reactions.

Nickel or phenanthroline mediated intramolecular arylation of sp3 C-H bonds using aryl halides.

The development of the intramolecular arylation of sp(3) C-H bonds adjacent to nitrogen using aryl halides is described. Arylation was accomplished using either Ni(COD)2 or 1,10-phenanthroline in substoichiometric amounts, and the reaction conditions were applied to a variety of electronically differentiated benzamide substrates. Preliminary studies suggest a mechanism involving aryl and alkyl radical intermediates.

Palladium-catalyzed intramolecular C-H arylation of arenes using tosylates and mesylates as electrophiles.

This paper describes a method for the palladium catalyzed intramolecular C-H arylation using tosylates and mesylates as electrophiles. The transformation is efficient for the synthesis of various heterocyclic motifs including furans, carbazoles, indoles, and lactams. Additionally, a protocol for the one-pot sequential tosylation/arylation of phenol derivatives is presented.

Prevalence and seasonal incidence of larval and adult cestode infections of sheep and goats in eastern Ethiopia.

A study on the prevalence and seasonal incidence of cestode parasite infections of sheep and goats was carried out in eastern Ethiopia for 2 years (May 2003-April 2005). During this period, viscera including liver, lungs, heart, kidneys and the gastro-intestinal tract were collected from 655 sheep and 632 goats slaughtered at four abattoirs located in the towns of Haramaya, Harar, Dire Dawa and Jijiga. At the abattoirs the abdominal, thoracic and pelvic cavities as well as the muscle surfaces of all animals were visually examined for the presence of larval (cystic) stages of cestode parasites. The viscera were transported within 24 h to the parasitology laboratory of Haramaya University and were examined for larval and adult cestodes following standard procedures. The most prevalent metacestodes (larval cestodes) were Cysticercus ovis (Taenia ovis), Cysticercus tenuicollis (T. hydatigena) and hydatid cysts (Echinococcus granulosus). In sheep, the overall prevalence was 26% for C. ovis, 79% for C. tenuicollis, and 68% for hydatid cysts. Similarly, for goats, the corresponding prevalence was 22%, 53% and 65%, respectively. The difference between sheep and goats in prevalence of C. tenuicollis was significant. The high prevalence of hydatid cysts in both sheep and goats indicates that cystic echinococcosis/hydatidosis is a public health problem in these regions which requires implementation of control measures, including public health education, strict meat inspection and control of stray dogs. The results of the survey also implies that infections of small ruminants with these metacestodes are responsible for condemnation of substantial quantities of affected organs and muscles and therefore of direct economic importance. Intestinal infections with adult tapeworms of Moniezia expansa, Avitellina centripunctata and Stilesia globipunctata, and bile duct infections with Stilesia hepatica were also common in both sheep and goats. In sheep, the overall prevalence of these tapeworms were 61%, 20%, 24% and 39%, respectively. Similarly, the overall prevalence of these parasites in goats was 53%, 21%, 27% and 36%, respectively.

Prevalence and seasonal incidence of nematode parasites and fluke infections of sheep and goats in eastern Ethiopia.

A 2-year abattoir survey was carried out to determine the prevalence, abundance and seasonal incidence of gastro-intestinal (GI) nematodes and trematodes (flukes) of sheep and goats in the semi-arid zone of eastern Ethiopia. During May 2003 to April 2005, viscera including liver, lungs and GI tracts were collected from 655 sheep and 632 goats slaughtered at 4 abattoirs located in the towns of Haramaya, Harar, Dire Dawa and Jijiga in eastern Ethiopia. All animals were raised in the farming areas located within the community boundaries for each town. Collected materials were transported within 24 h to the parasitology laboratory of Haramaya University for immediate processing. Thirteen species belonging to 9 genera of GI nematodes (Haemonchus contortus, Trichostrongylus axei, T. colubriformis, T. vitrinus, Nematodirus filicollis, N. spathiger Oesopha-gostomum columbianum, O. venulosum, Strongyloides papillosus, Bunostomum trigonocephalum, Trichuris ovis, Cooperia curticei and Chabertia ovina), and 4 species belonging to 3 genera of trematodes (Fasciola hepatica, F. gigantica, Paramphistomum {Calicohoron} microbothrium and Dicrocoelium dendriticum) were recorded in both sheep and goats. All animals in this investigation were infected with multiple species to varying degrees. The mean burdens of adult nematodes were generally moderate in both sheep and goats and showed patterns of seasonal abundance that corresponded with the bi-modal annual rainfall pattern, with highest burdens around the middle of the rainy season. In both sheep and goats there were significant differences in the mean worm burdens and abundance of the different nematode species between the four geographic locations, with worm burdens in the Haramaya and Harar areas greater than those observed in the Dire Dawa and Jijiga locations. Similar seasonal variations were also observed in the prevalence of flukes. But there were no significant differences in the prevalence of each fluke species between the four locations. Overall, the results showed that Haemonchus, Trichostrongylus, Nematodirus, Oesophagostomum, Fasciola and Paramphistomum species were the most abundant helminth parasites of sheep and goats in eastern Ethiopia.

Parasite control practices on Swedish horse farms.

BACKGROUND: Virtually all horses are infected with helminth parasites. For some decades, the control of parasites of Swedish horses has been based on routine treatments with anthelmintics, often several times per year. Since anthelmintic resistance is becoming an increasing problem it is essential to develop more sustainable control strategies, which are adapted to different types of horse management. The aim of this study was to obtain information on practices used by Swedish horse owners for the control of endoparasites. METHODS: A questionnaire with 26 questions about management practices and parasite control routines was posted to 627 randomly selected horse establishments covering most types of horse management in Sweden. RESULTS: The response rate was good in all categories of respondents (66-78%). A total of 444 questionnaires were used in the analyses. It was found that virtually all horses had access to grazing areas, usually permanent. Generally, pasture hygiene was infrequently practiced. Thirty-six percent of the respondents clipped or chain harrowed their pastures, whereas weekly removal of faeces from the grazing areas was performed by 6% of the respondents, and mixed or rotational grazing with other livestock by 10%. The number of anthelmintic treatments per year varied from 1-8 with an average of 3.2. Thirty-eight percent considered late autumn (Oct-Dec) to be the most important time for deworming. This finding, and an increased use of macrocyclic lactones in the autumn, suggests a concern about bot flies, Gasterophilus intestinalis. Only 1% of the respondents stated that faecal egg counts (FEC) were performed on a regular basis. The relatively high cost of FEC analyses compared to purchase of anthelmintics was thought to contribute to the preference of deworming without a previous FEC. From the study it was evident that all categories of horse owners took advice mainly from veterinarians. CONCLUSION: The results show that routines for endoparasite control can be improved in many horse establishments. To increase the knowledge of equine endoparasite control and follow the recommendations for how to reduce the spread of anthelmintic resistance, a closer collaboration between parasitologists and veterinary practitioners is desirable.

The effects of short-term feeding of fresh cassava (Manihot esculenta) foliage on gastrointestinal nematode parasite infections in goats in Cambodia.

The antiparasitic effect of cassava (Manihot esculenta Crantz) was tested in goats artificially infected with gastrointestinal parasitic nematodes. Each experimental group consisted of 6 pen-fed goats kept on a slatted floor. The treatments compared were: 1) controls fed grass only, 2) cassava replaced grass for 3 weeks from the commencement of larval dosing period, and 3) cassava replaced grass for 3 weeks after the worm infection was patent. A total of 2000 mixed-species infective nematode larvae (L3) were administered to each goat in four doses of 500 L3/day, commencing 5 weeks after removal of previously acquired infections with ivermectin. The faecal egg counts (FEC) reduced in both cassava fed groups during the time of feeding, compared to the controls. Although, FEC increased differently with time (P < 0.05), total adult worm burdens at slaughter (week 15) were not different between the treatment groups. No differences in live weight gain, or packed cell volume, between treatments were found. Whilst these results show limited evidence of an anthelmintic effect of cassava in the diet, they do suggest that feeding, or supplementation, of cassava over an extended period may prove beneficial.

Epidemiology and seasonal dynamics of gastrointestinal nematode infections of sheep in a semi-arid region of eastern Ethiopia.

A study on the epidemiology and seasonal dynamics of gastrointestinal nematode infections of sheep was carried out in a semi-arid region of eastern Ethiopia for 2.5 years (May 2003 to September 2005). The experimental flock comprised a total of 60 Black Head Ogaden sheep, consisting of four equal groups of young male and female and old male and female sheep. These grazed on communal pastures together with a larger university flock, as well as with animals owned by neighbouring small-holder farmers. A new experimental flock was established each year of the study. Parasitological data (EPG, faecal culture L3, PCV and FAMACHA estimates) and animal performance (weight change) were recorded each month on all experimental animals. In addition, four tracer lambs were assigned each month to the flock to determine the seasonal patterns of infective larvae acquired from pasture. Results showed distinct seasonal patterns associated with the bi-modal annual rainfall. High levels of infection occurred during the short and long rain seasons with peaks occurring in May and September of each year. Haemonchus contortus was the most prevalent parasite, followed by Trichostrongylus spp., with a number of other nematode species being occasionally recorded. H. contortus showed and increased propensity to undergo arrested development during the dry seasons. Correlations between EPG and PCV, EPG and FAMACHA eye scores, and PCV and FAMACHA eye scores were all highly significant (P<0.001). However, there was no significant association between the EPG and LW of the study animals during each study year. This information will provide a basis for developing epidemiologically based control strategies for gastrointestinal nematode parasites that are appropriate for flocks owned by small-holder farmers of semi-arid areas of eastern Ethiopia.

Prolonged persistence of fecally excreted ivermectin from reindeer in a sub-arctic environment.

In December 2001 and 2002, feces from reindeer calves treated with ivermectin were distributed on plots established on two types of forested reindeer pasture in northern Finland. The ungrazed plots were on an enclosure that had been fenced to prevent reindeer access for the last 6 years. The grazed plots were on an area that had been heavily stocked by reindeer during the last 5 years. After enclosures had been established, reindeer and large wildlife were prevented from entering by a fence. Topsoil samples (feces, vegetation, and soil) were collected monthly during the summers of the following 2 years, over a period of from 25 to 95 weeks after deposition. The samples were analyzed for ivermectin using HPLC. Although ivermectin degradation rapidly took place during the first spring, considerable residual ivermectin could be measured throughout the sampling time, showing that ivermectin in feces on pasture may not be photodegraded as rapidly as previously believed. The results support the need for further environmental evaluation studies on the use of ivermectin to control reindeer parasites.

Towards the implementation of the "basket of options" approach to helminth parasite control of livestock: emphasis on the tropics/subtropics.

The virtual reliance on anthelmintic drugs alone to control internal parasites of livestock is inappropriate and ultimately unsustainable. In the tropics and subtropics, widespread and high levels of anthelmintic resistance, particularly in nematode parasites of small ruminants, is rife. But more to the point, many farmers in these regions of the world are resource poor and cannot afford, or are reluctant to purchase drugs that may also be of dubious quality. As it is with any intervention, the benefits must outweigh the costs. This is not only in terms of conventional parameters such as reduced mortality and increasing productivity (meat, milk, fibre and traction power) of livestock, but also within the broad framework of helminths of veterinary/human importance, the aim should be a positive impact on reducing the threat of helminth zoonoses. However, understanding the issues involved and education of the end-users (farmers) is of fundamental importance, before any internal parasite control program should be promoted. Within the above context, we provide examples of how the "basket of options" approach could be adopted for the control of three quite disparate helminth problems in the tropics and subtropics, viz.: strongyle nematode infections of donkeys, the Taenia solium cysticercosis/taeniosis problem of pig and man and Haemonchus contortus infections in small ruminants. The "best practice" approaches can be defined as those "basket of options" that are practical, affordable, available and appropriate, whether to the commercial producer, or to the resource-poor farmer. Constraints that may restrict applying such options are accessibility to, and affordability of, suitable remedies and above all, the availability of information needed to make informed decisions in this regard.

Anthelmintic resistance of nematode parasites of small ruminants in eastern Ethiopia: exploitation of refugia to restore anthelmintic efficacy.

Faecal egg count reduction tests (FECRT) were conducted in May 2003 to determine the efficacy of anthelmintics used for treatment against nematode parasites in separately managed sheep and goat flocks at Alemaya University in eastern Ethiopia. These tests revealed high levels of anthelmintic resistance to albendazole, tetramisole, the combination of these two drugs, and to ivermectin in the goat flock (predominantly infected by Haemonchus contortus and Trichostrongylus spp.), whereas all drugs were highly efficacious in the sheep flock. A second FECRT confirmed these observations. Following this, a new management system was implemented on the goat flock for a period of 9 months (January-September 2004) in an attempt to restore the anthelmintic efficacy. This involved a combination of measures: eliminating the existing parasite infections in the goats, exclusion from the traditional goat pastures, and introducing communal grazing of the goats with the university sheep flock and livestock owned by neighbouring small-holder farmers. A second series of FECRTs (Tests 3 and 4) conducted 7 months after this change in management, showed high levels of efficacy to all three drugs (albendazole, tetramisole and ivermectin) in the goat flock. This is the first field study to demonstrate that anthelmintic efficacy in the control of nematode parasites of small ruminants can be restored by exploiting refugia.

Ethnoveterinary plant preparations as livestock dewormers: practices, popular beliefs, pitfalls and prospects for the future.

Ethnomedicine is an integral part of traditional medical practices in many countries of the developing world. A large proportion of the population uses this form of treatment for primary health care and for the treatment of ailments in their livestock. Livestock is a major asset for resource-poor smallholder farmers and pastoralists throughout the world and internal parasites are recognized by these communities as having an impact on livestock health. Parasitic infections are among those infections that traditional healers confidently treat and against which an enormous variety of remedies exist. Many of these are based on the use of plant preparations. Although various methods have been used for the validation of traditional phytomedical preparations, there is a lack of standardization of these procedures. The present study is aimed at providing an overview of ethnoveterinary deworming preparations, the various methods that have been used in their validation and the future prospects for their use against helminth parasites of ruminant livestock in developing countries, with an emphasis on nematode parasites. Recommendations are made on the procedures that should be followed to conduct in vivo and in vitro assays. Fostering better interaction between traditional healers and scientists is advocated to prevent harmful overexploitation, both of local knowledge and of plant species that may have effects against nematode parasites.

Nematode control in 'green' ruminant production systems.

Collectively, nematode parasites of domestic ruminants continue to pose the greatest disease problem in grazing livestock systems worldwide, despite the powerful and extensive chemotherapeutic arsenal available for their control. The widespread development of anthelmintic resistance, particularly in nematode parasites of small ruminants, and the trend towards non-chemical (ecological, organic, green) farming of livestock has provided an impetus for the research and development of alternative parasite control methods. This article provides a brief overview of the non-chemotherapeutic options for parasite control and how they might play a role either in organic farming or in other low-input farming systems.