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Journal of the American Chemical Society Mar 2003This paper reports the synthesis and characterization of a variety of ruthenium complexes coordinated with phosphine and N-heterocyclic carbene (NHC) ligands. These...
This paper reports the synthesis and characterization of a variety of ruthenium complexes coordinated with phosphine and N-heterocyclic carbene (NHC) ligands. These complexes include several alkylidene derivatives of the general formula (NHC)(PR(3))(Cl)(2)Ru=CHR', which are highly active olefin metathesis catalysts. Although these catalysts can be prepared adequately by the reaction of bis(phosphine) ruthenium alkylidene precursors with free NHCs, we have developed an alternative route that employs NHC-alcohol or -chloroform adducts as "protected" forms of the NHC ligands. This route is advantageous because NHC adducts are easier to handle than their free carbene counterparts. We also demonstrate that sterically bulky bis(NHC) complexes can be made by reaction of the pyridine-coordinated precursor (NHC)(py)(2)(Cl)(2)Ru=CHPh with free NHCs or NHC adducts. Two crystal structures are presented, one of the mixed bis(NHC) derivative (H(2)IMes)(IMes)(Cl)(2)Ru=CHPh, and the other of (PCy(3))(Cl)(CO)Ru[eta(2)-(CH(2)-C(6)H(2)Me(2))(N(2)C(3)H(4))(C(6)H(2)Me(3))], the product of ortho methyl C-H bond activation. Other side reactions encountered during the synthesis of new ruthenium alkylidene complexes include the formation of hydrido-carbonyl-chloride derivatives in the presence of primary alcohols and the deprotonation of ruthenium vinylcarbene ligands by KOBu(t). We also evaluate the olefin metathesis activity of NHC-coordinated complexes in representative RCM and ROMP reactions.
Topics: Alkenes; Crystallography, X-Ray; Heterocyclic Compounds; Hydrocarbons; Imidazoles; Ligands; Methane; Molecular Structure; Organometallic Compounds; Phosphines; Ruthenium; Triazoles
PubMed: 12603143
DOI: 10.1021/ja021146w -
Nature Mar 2019Carbon-hydrogen (C-H) and carbon-carbon (C-C) bonds are the main constituents of organic matter. Recent advances in C-H functionalization technology have vastly expanded...
Carbon-hydrogen (C-H) and carbon-carbon (C-C) bonds are the main constituents of organic matter. Recent advances in C-H functionalization technology have vastly expanded our toolbox for organic synthesis. By contrast, C-C activation methods that enable editing of the molecular skeleton remain limited. Several methods have been proposed for catalytic C-C activation, particularly with ketone substrates, that are typically promoted by using either ring-strain release as a thermodynamic driving force or directing groups to control the reaction outcome. Although effective, these strategies require substrates that contain highly strained ketones or a preinstalled directing group, or are limited to more specialist substrate classes. Here we report a general C-C activation mode driven by aromatization of a pre-aromatic intermediate formed in situ. This reaction is suitable for various ketone substrates, is catalysed by an iridium/phosphine combination and is promoted by a hydrazine reagent and 1,3-dienes. Specifically, the acyl group is removed from the ketone and transformed to a pyrazole, and the resulting alkyl fragment undergoes various transformations. These include the deacetylation of methyl ketones, carbenoid-free formal homologation of aliphatic linear ketones and deconstructive pyrazole synthesis from cyclic ketones. Given that ketones are prevalent in feedstock chemicals, natural products and pharmaceuticals, these transformations could offer strategic bond disconnections in the synthesis of complex bioactive molecules.
Topics: Acylation; Carbon; Hydrazines; Iridium; Ketones; Phosphines; Pyrazoles
PubMed: 30758326
DOI: 10.1038/s41586-019-0926-8 -
PloS One Dec 2006With the phasing out of ozone-depleting substances in accordance with the United Nations Montreal Protocol, phosphine remains as the only economically viable fumigant... (Comparative Study)
Comparative Study
BACKGROUND
With the phasing out of ozone-depleting substances in accordance with the United Nations Montreal Protocol, phosphine remains as the only economically viable fumigant for widespread use. However the development of high-level resistance in several pest insects threatens the future usage of phosphine; yet research into phosphine resistance mechanisms has been limited due to the potential for human poisoning in enclosed laboratory environments.
PRINCIPAL FINDINGS
Here we describe a custom-designed chamber for safely containing phosphine gas generated from aluminium phosphide tablets. In an improvement on previous generation systems, this chamber can be completely sealed to control the escape of phosphine. The device has been utilised in a screening program with C. elegans that has identified a phosphine synergist, and quantified the efficacy of a new fumigant against that of phosphine. The phosphine-induced mortality at 20 degrees C has been determined with an LC(50) of 732 ppm. This result was contrasted with the efficacy of a potential new botanical pesticide dimethyl disulphide, which for a 24 hour exposure at 20 degrees C is 600 times more potent than phosphine (LC(50) 1.24 ppm). We also found that co-administration of the glutathione depletor diethyl maleate (DEM) with a sublethal dose of phosphine (70 ppm,
CONCLUSIONS
The prohibitive danger associated with the generation, containment, and use of phosphine in a laboratory environment has now been substantially reduced by the implementation of our novel gas generation chamber. We have also identified a novel phosphine synergist, the glutathione depletor DEM, suggesting an effective pathway to be targeted in future synergist research; as well as quantifying the efficacy of a potential alternative to phosphine, dimethyl disulphide.
Topics: Animals; Caenorhabditis elegans; Disulfides; Drug Evaluation, Preclinical; Drug Resistance; Drug Synergism; Fumigation; Humans; Maleates; Phosphines
PubMed: 17205134
DOI: 10.1371/journal.pone.0000130 -
Journal of Medical Case Reports May 2022Aluminum phosphide (rice tablet) is a highly efficient agent for preserving grains against rodents and insects. It accounts for a large number of poisoning cases....
BACKGROUND
Aluminum phosphide (rice tablet) is a highly efficient agent for preserving grains against rodents and insects. It accounts for a large number of poisoning cases. Aluminum phosphide poisoning has a high mortality rate of about 90%, and to date, no antidote is available. It releases phosphine gas after exposure to moisture, and this reaction is catalyzed by the acidity of the stomach. Phosphine is then absorbed throughout the respiratory or gastrointestinal tracts and causes toxicity through inhibition of cytochrome c oxidase and formation of highly reactive free radicals. Treatment of patients with aluminum phosphide poisoning is supportive, including mechanical ventilation and vasopressors. The usage of infusion of glucose-insulin-potassium in rice tablet poisoning has been suggested, after its positive beneficial cardiac inotropic effects in patients with beta-blocker and calcium channel blocker poisoning.
CASE PRESENTATION
We report the case of a 30-year-old Iranian woman with critical aluminum phosphide poisoning, presented with hypotension and other signs of shock and severe metabolic acidosis, successfully treated with high-dose regular insulin and hypertonic dextrose and discharged from hospital in good condition. In contrast to our previous experiences, in which nearly all patients with critical aluminum phosphide poisoning died, this patient was saved with glucose-insulin-potassium.
CONCLUSION
Aluminum phosphide poisoning has a high mortality rate, and to date, no antidote is available. Administration of high-dose intravenous regular insulin and dextrose is suggested as a potential life-saving treatment for patients with critical aluminum phosphide poisoning.
Topics: Aluminum Compounds; Antidotes; Glucose; Humans; Hyperinsulinism; Insulin; Iran; Oryza; Phosphines; Potassium; Tablets
PubMed: 35578361
DOI: 10.1186/s13256-022-03425-4 -
Journal of Economic Entomology Aug 2012Phosphine gas, or hydrogen phosphide (PH3), is the most common insecticide applied to durable stored products worldwide and is routinely used in the United States for...
Phosphine gas, or hydrogen phosphide (PH3), is the most common insecticide applied to durable stored products worldwide and is routinely used in the United States for treatment of bulk-stored cereal grains and other durable stored products. Research from the late 1980s revealed low frequencies of resistance to various residual grain protectant insecticides and to phosphine in grain insect species collected in Oklahoma. The present work, which used the same previously established discriminating dose bioassays for phosphine toxicity as in the earlier study, evaluated adults of nine different populations of red flour beetle, Tribolium castaneum (Herbst), and five populations of lesser grain borer, Rhyzopertha dominica (F.) collected from different geographic locations in Oklahoma. One additional population for each species was a laboratory susceptible strain. Discriminating dose assays determined eight out of the nine T. castaneum populations, and all five populations of R. dominica, contained phosphine-resistant individuals, and highest resistance frequencies were 94 and 98%, respectively. Dose-response bioassays and logit analyses determined that LC99 values were approximately 3 ppm for susceptible and 377 ppm for resistant T. castaneum, and approximately 2 ppm for susceptible and 3,430 ppm for resistant R. dominica. The most resistant T. castaneum population was 119-fold more resistant than the susceptible strain and the most resistant R. dominica population was over 1,500-fold more resistant. Results suggest a substantial increase in phosphine resistance in these major stored-wheat pests in the past 21 yr, and these levels of resistance to phosphine approach those reported for other stored-grain pest species in other countries.
Topics: Animals; Female; Food Parasitology; Insecticide Resistance; Insecticides; Male; Oklahoma; Phosphines; Tribolium; Triticum
PubMed: 22928286
DOI: 10.1603/ec12064 -
BMC Genomics Nov 2015Phosphine is a valuable fumigant to control pest populations in stored grains and grain products. However, recent studies indicate a substantial increase in phosphine...
BACKGROUND
Phosphine is a valuable fumigant to control pest populations in stored grains and grain products. However, recent studies indicate a substantial increase in phosphine resistance in stored product pests worldwide.
RESULTS
To understand the molecular bases of phosphine resistance in insects, we used RNA-Seq to compare gene expression in phosphine-resistant and susceptible laboratory populations of the red flour beetle, Tribolium castaneum. Each population was evaluated as either phosphine-exposed or no phosphine (untreated controls) in triplicate biological replicates (12 samples total). Pairwise analysis indicated there were eight genes differentially expressed between susceptible and resistant insects not exposed to phosphine (i.e., basal expression) or those exposed to phopshine (>8-fold expression and 90 % C.I.). However, 214 genes were differentially expressed among all four treatment groups at a statistically significant level (ANOVA, p < 0.05). Increased expression of 44 cytochrome P450 genes was found in resistant vs. susceptible insects, and phosphine exposure resulted in additional increases of 21 of these genes, five of which were significant among all treatment groups (p < 0.05). Expression of two genes encoding anti-diruetic peptide was 2- to 8-fold reduced in phosphine-resistant insects, and when exposed to phosphine, expression was further reduced 36- to 500-fold compared to susceptible. Phosphine-resistant insects also displayed differential expression of cuticle, carbohydrate, protease, transporter, and many mitochondrial genes, among others. Gene ontology terms associated with mitochondrial functions (oxidation biological processes, monooxygenase and catalytic molecular functions, and iron, heme, and tetrapyyrole binding) were enriched in the significantly differentially expressed dataset. Sequence polymorphism was found in transcripts encoding a known phosphine resistance gene, dihydrolipoamide dehydrogenase, in both susceptible and resistant insects. Phosphine-resistant adults also were resistant to knockdown by the pyrethroid deltamethrin, likely due to the increased cytochrome P450 expression.
CONCLUSIONS
Overall, genes associated with the mitochondria were differentially expressed in resistant insects, and these differences may contribute to a reduction in overall metabolism and energy production and/or compensation in resistant insects. These data provide the first gene expression data on the response of phosphine-resistant and -susceptible insects to phosphine exposure, and demonstrate that RNA-Seq is a valuable tool to examine differences in insects that respond differentially to environmental stimuli.
Topics: Amino Acid Sequence; Animals; Cytochrome P-450 Enzyme System; Dihydrolipoamide Dehydrogenase; Genomics; Insecticide Resistance; Mitochondria; Molecular Sequence Data; Nitriles; Phosphines; Pyrethrins; Sequence Analysis, RNA; Transcriptome; Tribolium
PubMed: 26582239
DOI: 10.1186/s12864-015-2121-0 -
Molecules (Basel, Switzerland) Apr 2021Phosphine-borane complexes are novel chemical entities with preclinical efficacy in neuronal and ophthalmic disease models. In vitro and in vivo studies showed that the...
Phosphine-borane complexes are novel chemical entities with preclinical efficacy in neuronal and ophthalmic disease models. In vitro and in vivo studies showed that the metabolites of these compounds are capable of cleaving disulfide bonds implicated in the downstream effects of axonal injury. A difficulty in using standard in silico methods for studying these drugs is that most computational tools are not designed for borane-containing compounds. Using in silico and machine learning methodologies, the absorption-distribution properties of these unique compounds were assessed. Features examined with in silico methods included cellular permeability, octanol-water partition coefficient, blood-brain barrier permeability, oral absorption and serum protein binding. The resultant neural networks demonstrated an appropriate level of accuracy and were comparable to existing in silico methodologies. Specifically, they were able to reliably predict pharmacokinetic features of known boron-containing compounds. These methods predicted that phosphine-borane compounds and their metabolites meet the necessary pharmacokinetic features for orally active drug candidates. This study showed that the combination of standard in silico predictive and machine learning models with neural networks is effective in predicting pharmacokinetic features of novel boron-containing compounds as neuroprotective drugs.
Topics: Blood-Brain Barrier; Boranes; Computer Simulation; Humans; Machine Learning; Neuroprotection; Neuroprotective Agents; Phosphines; Protein Binding
PubMed: 33923006
DOI: 10.3390/molecules26092505 -
Pest Management Science Oct 2023The fumigant phosphine is used all over the world for disinfestation of stored grains and commodities. Adults of 23 different populations of Tribolium castaneum from 10...
BACKGROUND
The fumigant phosphine is used all over the world for disinfestation of stored grains and commodities. Adults of 23 different populations of Tribolium castaneum from 10 different countries were evaluated for phosphine resistance using a modification of the Detia Degesch Phosphine Tolerance Test Kit (DDPTTK). Adults were exposed to 3000 ppm and recorded for 5-270 min for their mobility.
RESULTS
Among the tested populations, high levels of phosphine resistance were recorded in populations from Brazil, Serbia, and Spain. No survivals were recorded after 7 days post exposure for eight of 23 in a tested population.
CONCLUSIONS
Our work revealed four scenarios: 1, quick knockdown-low (or no) recovery; 2, Slow knockdown-high recovery; 3, Quick knockdown-high recovery; and 4, Slow knockdown-low recovery. Our data indicate that post exposure period is critical for the evaluation and characterization of phosphine resistance. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Topics: Animals; Coleoptera; Insecticide Resistance; Tribolium; Phosphines; Insecticides
PubMed: 37226656
DOI: 10.1002/ps.7555 -
Organic Letters Sep 2018Cyclopropenethiones are reported as new bioorthogonal reagents. These motifs react readily with substituted phosphines to provide thiocarbonyl adducts. In some cases,...
Cyclopropenethiones are reported as new bioorthogonal reagents. These motifs react readily with substituted phosphines to provide thiocarbonyl adducts. In some cases, the ligations are >300-fold faster than analogous reactions with bioorthogonal cyclopropenones. Dialkyl cyclopropenethiones are also stable in aqueous buffers and can be used for biomolecule labeling in vitro and in cell lysate. The rapid reactivity and biocompatibility of cyclopropenethiones suggest that they will be useful probes for cellular studies.
Topics: Cyclopropanes; Molecular Structure; Phosphines; Quantum Theory; Thiones
PubMed: 30207474
DOI: 10.1021/acs.orglett.8b02296 -
Scientific Reports Aug 2017Cryptolestes ferrugineus is a serious pest of stored grain and has developed high levels of resistance to phosphine fumigants in many countries. Measuring differences in...
Reference gene selection to determine differences in mitochondrial gene expressions in phosphine-susceptible and phosphine-resistant strains of Cryptolestes ferrugineus, using qRT-PCR.
Cryptolestes ferrugineus is a serious pest of stored grain and has developed high levels of resistance to phosphine fumigants in many countries. Measuring differences in expression levels of certain 'resistant' genes by quantitative real-time PCR (qRT-PCR) may provide insights into molecular mechanisms underlying resistance to phosphine in C. ferrugineus, but reliable qRT-PCR results depend on suitable reference genes (RGs). We evaluated the stability of nine candidate RGs across different developmental stages and phosphine strains of C. ferrugineus, using four softwares. The results showed that RPS13 and EF1α were the most stable RGs, whereas α-TUB was the least under developmental stages. Across the different strains, RPS13 and γ-TUB were the most stable RGs, whereas CycA and GAPDH were the least. We confirmed the reliability of the selected RGs by qRT-PCR analyses of the mitochondrial cox1 gene. Expression of cox1 was not significantly different in the phosphine-resistant strain compared with the phosphine-susceptible strain, but three mitochondrial genes (nad3, atp6 and cob) were significantly down-regulated. These results suggest that alterations in the expressions of these three genes may be associated with phosphine resistance in C. ferrugineus. The findings will facilitate future functional genomics studies on the development and phosphine resistance in C. ferrugineus.
Topics: Animals; Coleoptera; Gene Expression Profiling; Insecticide Resistance; Insecticides; Mitochondria; Phosphines; Real-Time Polymerase Chain Reaction; Reference Standards
PubMed: 28765619
DOI: 10.1038/s41598-017-07430-2