Chiral separation machinery using new crystalline inclusion hosts: Match/mismatch in the enantiomer recognition of (R,S)-1-methoxy-2-propanol effected by a borneol/fenchol building block exchange in the host molecule

New chiral host molecules 1 and 2 involving a bulky terpenoid unit and aromatic ethyne spacer groups were synthesized using Pd-catalyzed cross-coupling reactions of (+)-2α-ethynyl-2β-hydroxybornane (4) or (+)-2α-ethynyl-2β-hydroxyfenchane (5) with 9,10-dibromoanthracene. Host compounds 1 and 2 from crystalline inclusions with 1-methoxy-2-propanol (3) in 1:1 and 1:2 stoichiometry, respectively. In the case of 1, complete enantiomer resolution (ee > 99%) of 3 is effected in one cocrystallization step. However, constitutional isomer 2 failed in the enantiomer separation of 3, which might be explained due to the different crystal lattice buildup of these cocrystals. Chirality 9:203–210, 1997. © 1997 Wiley-Liss, Inc.     

Fate of 3-Allyloxy-1,2-benzisothiazole 1,1-Dioxide (Oryzemate®) in Rice Plants

Studies on absorption, translocation and metabolism of 3-allyloxy-1,2-benzisothiazole 1,1-dioxide (Oryzemate), a new rice blast controlling agent, in rice plants were undertaken using the ³⁵S-labeled preparation. Oryzemate was administrated to the plants by liquid application. Uptake of labeled compound into rice plants was demonstrated by autoradiography and quantitative ³⁵S-analyses. Preferential accumulation of radioactive compounds in the leaves was observed. The metabolites in the plants were identified as allyl o-sulfamoylbenzoate, saccharin and N-d-glucopyranosylsaccharin by cochromatography and cocrystallization with synthesized authentic compounds. Most of ³⁵S-labeled compounds accumulated in the plants were saccharin and N-d-glucopyranosylsaccharin. A small amount of allyl o-sulfamoylbenzoate was detected and Oryzemate was detectable in trace quantities at all harvest.     

In silico screening of dicarboxylic acids for cocrystallization with phenylpiperazine derivatives based on both cocrystallization propensity and solubility advantage

In silico screening was performed to search for binary solids in which a phenylpiperazine-derivative drug was cocrystallized with a dicarboxylic acid. The phenylpiperazine derivative could be any of 61 such drugs, while the dicarboxylic acid could be any of nine such acids. The uniqueness of this approach was that two criteria had to be fulfilled simultaneously, namely a high propensity for cocrystallization and a sufficient solubility advantage. Using the mixing enthalpies of selected pairs of crystal formers with high affinities for one another permitted the classification of candidates with a high probability of cocrystallization. Further modeling of the solubility advantage allowed the identification of many binary solids that potentially exhibit significantly enhanced solubility in water. Based on the computed values for the mixing enthalpies and solubility advantage factors, it was concluded that dicarboxylic acids are both excellent coformers for cocrystallization with phenylpiperazines and very good solubility enhancers; indeed, the use of dicarboxylic acids as coformers would allow the degree of dissolution to be tuned for many of the studied drugs. The observed similarities of the cocrystallization landscapes of the studied drugs and excipients were also explored.     

Enzyme inhibitor modeling with TpZn complexes of functional hydroxamates and oximates

Salicylhydroxamic acid reacts with the enzyme model Tp^Ph,MeZn-OH to form the O,O-chelating hydroxamate complex 1. The hydrogen bonding capacity of zinc enzyme bound hydroxamates is reproduced by cocrystallization of two molecules if 1 with two molecules of methanol and by cocrystallization of one molecule of Tp^Ph,MeZn-acetohydroxamate with one molecule of 3-phenyl-5-methylpyrazole. The complex formed from Tp^Ph,MeZn-OH and N-tosylproline hydroxamic acid, according to its spectra, contains the hydroxamate as an N,N-chelating ligand. In contrast, the oximate derived from pyruvic aldehyde does not act as a chelating ligand, but is monodentate via the oximate oxygen.     

Host range of Peronospora somniferi and Pe. meconopsidis within selected members of the Papaveraceae under controlled conditions

Opium poppy, belonging to the family Papaveraceae, is grown for its alkaloid compounds of pharmaceutical value. Downy mildew caused by Peronospora somniferi and Pe. meconopsidis, substantially impacts crop production. The present study was conducted to identify the host range of Pe. somniferi and Pe. meconopsidis within selected weed and ornamental members of the Papaveraceae family. Nine Papaver spp., Meconopsis cambrica and a nonhost control (tomato, Solanum lycopersicum) were challenged with both pathogens under controlled glasshouse or laboratory conditions using infested soil or foliar applied sporangia as inocula. Peronospora somniferi and Pe. meconopsidis induced disease symptoms, including sporulation, in at least one trial for all tested species except for Pa. atlanticum and tomato. Species-specific PCR testing of foliage of challenged plants confirmed infections by both pathogen species of symptomatic plants, identifying these as hosts. Positive PCR tests were also obtained from Pa. atlanticum plants for both pathogens. However, in the absence of pathogen sporulation structures as further evidence of infection, the host status of Pa. atlanticum remains inconclusive. Testing of seeds collected from Pe. somniferi and Pe. meconopsidis infected plants of Pa. somniferum, Pa. dubium, Pa. rhoeas and Pa. nudicaule showed presence of both pathogens, indicating likely ability for seed transmission in these species. We identified new hosts of these pathogens and discuss potential implications of these alternative hosts in pathogen survival, dissemination and epidemic initiation.     

Formation of Itraconazole–Succinic Acid Cocrystals by Gas Antisolvent Cocrystallization

Cocrystals of itraconazole, an antifungal drug with poor bioavailability, and succinic acid, a water-soluble dicarboxylic acid, were formed by gas antisolvent (GAS) cocrystallization using pressurized CO₂ to improve itraconazole dissolution. In this study, itraconazole and succinic acid were simultaneously dissolved in a liquid solvent, tetrahydrofuran, at ambient conditions. The solution was then pressurized with CO₂, which decreased the solvating power of tetrahydrofuran and caused crystallization of itraconazole–succinic acid cocrystals. The cocrystals prepared by GAS cocrystallization were compared to those produced using a traditional liquid antisolvent, n-heptane, for crystallinity, chemical structure, thermal behavior, size and surface morphology, potential clinical relevance, and stability. Powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, and scanning electron microscopy analyses showed that itraconazole–succinic acid cocrystals with physical and chemical properties similar to cocrystals produced using a traditional liquid antisolvent technique can be prepared by CO₂ antisolvent cocrystallization. The dissolution profile of itraconazole was significantly enhanced through GAS cocrystallization with succinic acid, achieving over 90% dissolution in less than 2 h. The cocrystals appeared stable against thermal stress for up to 4 weeks under accelerated stability conditions, showing only moderate decreases in their degree of crystallinity but no change in their crystalline structure. This study shows the utility of an itraconazole–succinic acid cocrystal for improving itraconazole bioavailability while also demonstrating the potential for CO₂ to replace traditional liquid antisolvents in cocrystal preparation, thus making cocrystal production more environmentally benign and scale-up more feasible.KEY WORDS: cocrystals, dissolution rate, gas antisolvent, itraconazole     

姜黄素类化合物生物合成研究进展

姜黄素类化合物是植物中一类稀少的二酮类化合物,存在于姜科、天南星科植物的块根或根茎中,是姜黄等植物中主要活性成分,因具有抗氧化、抗癌等诸多药理活性而被广泛应用于食品领域和新药研发中.因其苯环侧链取代基不同,姜黄素类化合物可进一步分为姜黄素、去甲氧基姜黄素、双去甲氧基姜黄素等.目前,姜黄素类化合物主要是通过植物提取法获得...     

Stereoselectivity in the Salt–Cocrystal Products formed by Phenylglycinol or Phenylglycine with their Respective Sodium or Hydrochloride Salts

The salt and stereoselective cocrystal phenomena associated with 2‐phenylglycinol and 2‐phenylglycine have been studied using X‐ray powder diffraction and differential scanning calorimetry. The chiral identities of the free acids and their sodium salts, or the free bases and their chloride salts, were found to play a determining role as to whether a salt–cocrystal product could or could not be formed. In particular, when cocrystallization of an enantiomerically pure basic or zwitterionic substance with its enantiomerically pure acid addition salt was attempted, a salt–cocrystal was only obtained when the absolute configuration of the two reactants is opposite. On the other hand, it has been found that no stereoselectivity in salt–cocrystal formation existed in the cocrystallization of an enantiomerically pure acidic or zwitterionic substance with its enantiomerically pure base addition salt. Chirality 25:8–15, 2013. © 2012 Wiley Periodicals, Inc.     

Bee species and their associated flowers in the French West Indies (Guadeloupe,Les Saintes,La Désirade,Marie Galante,St Barthelemy and Martinique) (Hymenoptera: Anthophila: Apoidea)

A list of 25 bee species in the families Apidae and Megachilidae is provided for the French West Indies (FWI) along with floral host records from 260 plant species in 71 families. Four species are newly recorded for some islands, as follows: Coelioxys abdominalis Guérin, 1844, new island record for Marie-Galante and Martinique, Centris decolorata Lepeletier, 1841, new island record for Marie-Galante, Melissodes rufodentatus Smith, 1854, is newly recorded from Guadeloupe and Mesoplia azurea (Lepeletier & Serville, 1825) from La Désirade. The bee fauna of the FWI is mostly composed of species that occur (or may be expected to occur) throughout much of the West Indies, combined with species that are widely distributed on the mainland and a proportion of regionally endemic species. In addition to these elements, there appear to be at least a few locally endemic species. A few species of bees appear to be oligolectic; their host plants, however, are visited by a wide variety of bees and other insects. There is only one intentionally introduced bee in Guadeloupe, the European honey bee Apis mellifera Linnaeus, 1758, and three non-native bees that reached the FWI from other parts of the Caribbean and the mainland: Megachile (Pseudomegachile) lanata (Fabricius, 1775), M. (Callomegachile) rufipennis (Fabricius, 1793) and M. (Eutricharaea) concinna Smith, 1879. Honey bees are often extremely abundant, and dominate nectar and pollen resources in ways that are disruptive to native bees. Although it is easy to observe individual honey bees displacing individual native bees on flowers, there are no data on the ecological effects of honey bees on native pollinators in the FWI.     

Saprolegnia strains isolated from river insects and amphipods are broad spectrum pathogens

Saprolegnia species are destructive pathogens to many aquatic organisms and are found in most parts of the world. Reports based on phylogenetic analysis suggest that Saprolegnia strains isolated from aquatic animals such as crustaceans and frogs are close to Saprolegnia strains isolated from infected fish or fish eggs and vice versa. However, it has often been assumed that host specificity occurs for each individual isolate or strain. Here we demonstrate that Saprolegnia spp. can have multiple hosts and are thus capable of infecting different aquatic organisms. Saprolegnia delica, Saprolegnia hypogyna, and 2 strains of Saprolegnia diclina were isolated from aquatic insects and amphipods while S. delica, Saprolegnia ferax, Pythium pachycaule, and a Pythium sp. were isolated from the water of a medium to fast flowing river. The ITS region of the rRNA gene was sequenced for all isolates. In challenge experiments, all four isolates from insects were found to be highly pathogenic to eggs of Atlantic salmon (Salmo salar) and embryos of the African clawed frog (Xenopus laevis). We found that Saprolegnia spp. isolated from salmon eggs were also able to successfully establish infection in nymphs of stonefly (Perla bipunctata) and embryos of X. laevis). These results suggest that Saprolegnia spp. are capable of infecting multiple hosts, which may give them an advantage during seasonal variation in their natural environments.     

A biosensor-based approach toward purification and crystallization of G protein-coupled receptors

Biacore technology was used to develop an affinity purification method and screen cocrystallization conditions for the chemokine receptor CCR5. We characterized the binding of nine HIV gp120 variants and identified a truncated construct (YU2DV1V2) that bound CCR5 independent of CD4. This construct was used in an affinity purification step to improve the activity of detergent-solubilized receptor by approximately 300%. The biosensor was also used to screen receptor binding activity automatically under 50 different crystallization conditions. We found that high-molecular-weight polyethylene glycols (PEGs 4,000 and 8,000 Da) most often stabilized the receptor and improved complex formation with potential cocrystallization partners such as conformationally sensitive monoclonal antibodies and gp120. Our results show how biosensors can provide unique insights into receptor purification methods and reveal the effects of crystallization conditions on complex formation. Importantly, these methods can be readily applied to other systems.     

Comparison of crystal and solution hemoglobin binding of selected antigelling agents and allosteric modifiers

This paper details comprehensive binding studies (solution and X-ray) of human hemoglobin A with a group of halogenated carboxylic acids that were investigated as potential antisickling agents. It is, to our knowledge, the first study to compare solution and crystal binding for a series of compounds under similar high-salt conditions used for cocrystallization. The compounds include [(3,4-dichlorobenzyl)oxy]acetic acid, [(p-bromobenzyl)oxy]acetic acid, clofibric acid, and bezafibrate. The location and stereochemistry of binding sites have been established by X-ray crystallography, while the number of binding sites and affinity constants were measured by using equilibrium dialysis. The solution binding studies were conducted with deoxygenated hemoglobin and carbonmonoxyhemoglobin with low (50 mM) and high (2 M) salt concentrations. It was concluded that the observed crystal structures are consistent with the binding observed in solution and that the number of binding sites is independent of salt concentration, while the binding constant increases with increasing salt concentration. The studies also reveal that relatively small changes in the chemical structure of a drug molecule can result in entirely different binding sites on the protein. Moreover, the X-ray studies provide a possible explanation for the multiplicity in function exhibited by these compounds as allosteric modulators and/or antisickling agents. Finally, the studies that these compounds bind differently to the R and T states of hemoglobin, an observation of special significance to the original design of these agents.     

黑龙江省蜜环菌生物种的地理分布概况

自1999年至2002年间对黑龙江省境内几个主要林区中的蜜环菌生物种进行了调查、采集和鉴定,并对其寄主种类和子实体发生规律以及地理分布特点进行了总结分析。结果表明:黑龙江省境内至少存在5个蜜环菌生物种,即芥黄蜜环菌Armillaria sinapina,高卢蜜环菌A.gallica,黄盖蜜环菌A.luteopileata,奥氏蜜环菌A.ostoyae和中国生物种F;寄主包括10个针叶和阔叶树种;与其他几种蜜环菌生物种相比较,A.gallica是黑龙江省境内出现概率最大的一个生物种;根据采集经验发现,温度和湿度是影响子实体发生的主要因子。     

To grow or not to grow? Intermediate and paratenic hosts as helminth life cycle strategies

Larval helminths in intermediate hosts often stop growing long before their growth is limited by host resources, and do not grow at all in paratenic hosts. We develop our model [Ball, M.A., Parker, G.A., Chubb, J.C., 2008. The evolution of complex life cycles when parasite mortality is size- or time-dependent. J. Theor. Biol. 253, 202-214] for optimal growth arrest at larval maturity (GALM) in trophically transmitted helminths. This model assumes that on entering an intermediate host, larval death rate initially has both time- (or size-) dependent and time-constant components, the former increasing as the larva grows. At GALM, mortality changes to a new and constant rate in which the size-dependent component is proportional to that immediately before GALM. Mortality then remains constant until death or transmission to the definitive host. We analyse linear increasing and accelerating forms for time-dependent mortality to deduce why there is sometimes growth (intermediate hosts) and sometimes no growth (paratenic hosts). Calling i the intermediate or paratenic host, and j the definitive host, conditions favouring paratenicity are: (i) high values in host i for size at establishment, size-related mortality, expected intensity, (ii) low values in host i for size-independent mortality rate, potential growth rate, transmission rate to j, and ratio of death rate in j/growth rate in j. Opposite conditions favour growth in the (intermediate) host, either to GALM or until death without GALM. We offer circumstantial evidence from the literature supporting some of these predictions. In certain conditions, two of the three possible growth strategies (no growth; growth to an optimal size then growth arrest (GALM); unlimited growth until larval death) can exist as local optima. The effect of the discontinuity in death rate after GALM is complex and depends on mortality and growth parameters in the two hosts, and on the mortality functions before and after GALM.     

High temperatures are not responsible for lack of infection of citrus roots by Phytophthora citrophthora during the summer,but suppressive soil microorganisms may inhibit infection by P. citrophthora

In regions with a mediterranean climate such as southern California, P. citrophthora infection of citrus does not normally occur during the summer. However, in this study, P. citrophthora was isolated abundantly from alternative hosts planted in an infested citrus grove, in the middle of the summer. Citrus root infection from P. citrophthora did occur in this study but it was extremely low. Citrus seedlings grown in autoclaved soil from Pauma Valley, artificially infested with P. citrophthora, contained significantly higher levels of infection than seedlings grown in infested, non-autoclaved, soil or in part autoclaved, part non-autoclaved, infested soil. This suggests that the Pauma Valley soil contains microorganisms naturally suppressive to P. citrophthora.The low occurrence of P. citrophthora infection of citrus roots during the summer may be partially due to soil microorganisms associated with the citrus host and not the inability of P. citrophthora to grow well at the soil temperatures found during the summer in southern California.     

Natural Infection by Tospoviruses of Cucurbitaceous and Fabaceous Vegetable Crops in India

Natural infection of tospoviruses on three cucurbitaceous (Cucumis sativus, cucumber; Luffa acutangula, ridge gourd; Citrullus lanatus, watermelon) and three fabaceous (Vigna unguiculata, cowpea; Phaseolus vulgaris, French bean; Dolichos lablab, sem) vegetable crops in India was identified on the basis of nucleocapsid protein (NP) gene characteristics. The complete NP gene of the cowpea isolate from Kerala and the sem isolate from Tamil Nadu was 831 nucleotides long, encoding a protein of 276 amino acids. For other Tospovirus isolates from cucumber, French bean, ridge gourd and watermelon, the partial NP gene (291 nt) was sequenced. Comparative NP gene sequence analyses revealed that fabaceous isolates shared maximum identity both at the nucleotide (92–97%) and amino acid (93–97%) levels with the corresponding region of Groundnut bud necrosis virus (GBNV), whereas cucurbitaceous isolates shared maximum identity both at nucleotide (93–99%) and amino acid (95–98%) levels with the corresponding region of Watermelon bud necrosis virus (WBNV), results suggesting that the Tospovirus isolates infecting fabaceous hosts should be regarded as strain of GBNV, whereas those infecting cucurbitaceous hosts as a strain of WBNV. Nucleocapsid protein gene was conserved both in GBNV and WBNV isolates originating from different hosts and locations.     

Nitrogenous compounds of the body fluids of usual and unusual gastropod hosts of larval trematodes

Body fluid was analyzed for nitrogenous compounds in four selected fresh water gastropods. Striking differences were noted in the levels of total nitrogen (TN), protein nitrogen (PN), and nonprotein nitrogen (NPN) among the four snails studied.     

Intense Chiral Optical Phenomena in Racemic Polymers by Cocrystallization With Chiral Guest Molecules: A Brief Overview

This review is devoted to the chiral optical behavior of films of racemic polymers whose chirality is induced by cocrystallization with nonracemic (also temporary) guest molecules. We provide examples of macromolecular amplification of chirality, produced by molecular and supramolecular mechanisms, on industrially relevant polymers like poly(2,6‐dimethyl‐1,4‐phenylene)oxide (PPO) and syndiotactic polystyrene (s‐PS). Chirality 28:29–38, 2016. © 2015 Wiley Periodicals, Inc.     

Biogeographical patterns of marine larval trematode parasites in two intermediate snail hosts in Europe

Aim We used published inventories of trematodes in Littorina littorea (L.) and Hydrobia ulvae (Pennant) in European seas to search for two basic biogeographical patterns in the spatial occurrence of various trematode species: (1) do parasite distribution and richness patterns in the two host snails overlap with known ecoregions of free‐living organisms; and (2) does trematode species richness in the snails follow latitudinal or longitudinal gradients? Location North East Atlantic. Methods We used multidimensional scaling (MDS), analysis of similarity (ANOSIM) and analysis of variance (ANOVA) to test whether there were overlaps of parasite distribution and richness with known ecoregions of free‐living organisms. In addition, we used linear regression analyses to test whether trematode richness in snails (corrected for sampling effort) was correlated with the latitude or longitude of the sampling sites. Results When corrected for sampling effort, mean trematode species richness per site did not differ among the different ecoregions in L. littorea. In contrast, in H. ulvae, mean species richness was much lower for sites from the Celtic Sea compared with sites from the Baltic Sea and the North Sea. Based on the results of MDS analyses, trematode species composition was distinct among ecoregions; in particular, communities from the Baltic Sea differed markedly from communities in the Celtic Sea, for both snail species. Latitude and longitude were not significantly correlated with parasite species richness in either snail species. Most trematode species had restricted distributions, and only three species in L. littorea and five species in H. ulvae occurred at more than 50% of the sites. Main conclusions There is more structure in the large‐scale distribution of trematodes in gastropods than one would expect from the large‐scale dispersal capabilities of their bird and fish final hosts. We propose mechanisms based both on limited dispersal via fish and bird final hosts and on gradients in environmental factors to explain the observed patterns.     

The tribe Bryocorini (Insecta: Heteroptera: Miridae: Bryocorinae): phylogeny,description of a new genus,and adaptive radiation on ferns

A cladistic analysis of the tribe Bryocorini based on 68 morphological characters is conducted. Bryocorini are supported as a monophyletic group with Eccritotarsini as their sister taxon. Based on the phylogenetic analysis, we redefine the tribe Bryocorini to contain the following seven genera: Bryocorella Carvalho, 1956, Bryocoris Fallén, 1829, Bryophilocapsus Yasunaga, 2000, Cobalorrhynchus Reuter, 1906 gen. dist., D iplazicoris gen. nov. , Hekista Kirkaldy, 1902, and Monalocoris Dahlbom, 1851. The genus Bryocorella is transferred to Bryocorini from the tribe Eccritotarsini. The subgenus Cobalorrhynchus is treated as a separate genus. Diplazicoris is described as monotypic to accommodate D iplazicoris lombokianus sp. nov. An updated diagnosis of the tribe, a key to genera, and a diagnosis of each recognized genus are presented. Selected photomicrographs, scanning micrographs, and illustrations of the pretarsus, metepisternal scent efferent system, metafemoral trichobothria, and morphology of head, pronotum, and male and female genitalia are provided. Mapping of the host data on the revealed tree shows that Bryocorini represent one of the very few currently known examples of the adaptive radiation of a fairly large insect group on ferns. © 2015 The Linnean Society of London