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Chemical Society Reviews May 2003This manuscript summarizes the results of studies on the application of the reaction of dialkyl (aryl) phosphoramidate anions with carbonyl electrophiles for... (Review)
Review
This manuscript summarizes the results of studies on the application of the reaction of dialkyl (aryl) phosphoramidate anions with carbonyl electrophiles for stereospecific synthesis of P-chiral biophosphates (Stec reaction). Following the results obtained with organic phosphoramidates which delineated the scope of the reaction and its stereochemical course, the application of the title reaction is presented for the preparation of diastereomerically pure P-chiral cyclic nucleotide analogues (phosphorothioates, phosphoroselenoates, phosphoroselenothioates, isotopomeric 18O-phosphates), and P-chiral nucleoside monophosphate analogues, as well as dinucleoside phosphate analogues (phosphorothioates, methanephosphonates).
Topics: Amides; Chemistry, Organic; Nucleotides; Organophosphates; Phosphoric Acids; Stereoisomerism
PubMed: 12792939
DOI: 10.1039/b207207f -
ACS Applied Materials & Interfaces May 2022A nanoreactor containing an evolved mutant of phosphotriesterase (L72C/Y97F/Y99F/W263V/I280T) as a catalytic bioscavenger was made for detoxification of...
A nanoreactor containing an evolved mutant of phosphotriesterase (L72C/Y97F/Y99F/W263V/I280T) as a catalytic bioscavenger was made for detoxification of organophosphates. This nanoreactor intended for treatment of organophosphate poisoning was studied against paraoxon (POX). Nanoreactors were low polydispersity polymersomes containing a high concentration of enzyme (20 μM). The polyethylene glycol-polypropylene sulfide membrane allowed for penetration of POX and exit of hydrolysis products. simulations under second order conditions showed that 1 μM enzyme inactivates 5 μM POX in less than 10 s. LD-shift experiments of POX-challenged mice through intraperitoneal () and subcutaneous () injections showed that intravenous administration of nanoreactors (1.6 nmol enzyme) protected against 7 × LD . in prophylaxis and 3.3 × LD in post-exposure treatment. For mice -challenged, LD shifts were more pronounced: 16.6 × LD in prophylaxis and 9.8 × LD in post-exposure treatment. Rotarod tests showed that transitory impaired neuromuscular functions of challenged mice were restored the day of experiments. No deterioration was observed in the following days and weeks. The high therapeutic index provided by prophylactic administration of enzyme nanoreactors suggests that no other drugs are needed for protection against acute POX toxicity. For post-exposure treatment, co-administration of classical drugs would certainly have beneficial effects against transient incapacitation.
Topics: Animals; Mice; Nanotechnology; Organophosphate Poisoning; Organophosphates; Paraoxon; Phosphoric Triester Hydrolases
PubMed: 35440137
DOI: 10.1021/acsami.2c03210 -
Mutation Research 1979
Comparative Study Review
Topics: Animals; Carcinogens; Chromosome Aberrations; Drosophila melanogaster; Female; Fertility; Genes, Dominant; Genes, Lethal; Male; Mutagens; Mutation; Organophosphates; Organophosphorus Compounds; Salmonella typhimurium; Species Specificity
PubMed: 112474
DOI: 10.1016/0165-1110(79)90002-2 -
Chemico-biological Interactions May 1999We show here with a congeneric series of Rp- and Sp-alkoxymethyl phosphonothiolates of known absolute stereochemistry that chiral selectivity in their reaction with... (Review)
Review
We show here with a congeneric series of Rp- and Sp-alkoxymethyl phosphonothiolates of known absolute stereochemistry that chiral selectivity in their reaction with acetylcholinesterase can be described in terms of discrete orientational and steric requirements. Stereoselectivity depends on acyl pocket dimensions, which govern leaving group orientation and a productive association of the phosphonyl oxygen in the oxyanion hole. Overall geometry is consistent with a pentavalent intermediate where the attacking serine and leaving group are at apical positions. Oxime reactivation of the phosphonylated enzyme occurs through a similar associative intermediate presumably forming an oxime phosphonate. The oximes of differing structure show distinct angles of attacking the phosphate where the attack angles and access to the phosphorus are constrained in the sterically impacted gorge. Hence, efficacy of oxime reactivation is dependent on both oxime and conjugated phosphonate structures.
Topics: Animals; Binding Sites; Cholinesterase Inhibitors; Cholinesterases; Enzyme Activation; Enzyme Reactivators; Humans; Models, Molecular; Organophosphates; Protein Conformation; Stereoisomerism; Structure-Activity Relationship; Thermodynamics
PubMed: 10421434
DOI: 10.1016/s0009-2797(99)00009-5 -
Organic Letters Aug 2012Glycosyl 1-phosphates enriched in the α-anomer are obtained without the use of protecting groups in two steps starting from the free hemiacetal. Condensation of free...
Glycosyl 1-phosphates enriched in the α-anomer are obtained without the use of protecting groups in two steps starting from the free hemiacetal. Condensation of free hemiacetals with toluenesulfonylhydrazide yields a range of glycosylsulfonohydrazide donors which can be oxidized using cupric chloride in the presence of phosphoric acid and the coordinating additive 2-methyl-2-oxazoline to give useful yields of the fully deprotected glycosyl 1-phosphates.
Topics: Combinatorial Chemistry Techniques; Copper; Glycosides; Glycosylation; Molecular Structure; Organophosphates; Phosphoric Acids; Stereoisomerism
PubMed: 22846058
DOI: 10.1021/ol3019083 -
Environment International Oct 2021Over the course of the continual phase-outs of toxic halogenated flame retardants (HFRs), there has been an increasing demand for organophosphate esters (OPEs) in global... (Review)
Review
Over the course of the continual phase-outs of toxic halogenated flame retardants (HFRs), there has been an increasing demand for organophosphate esters (OPEs) in global FR markets. OPE-FRs have largely been identified as OP triesters, which have a basic chemical structure of O = P(OR). In addition to OP triesters, OPEs can refer to another class of related substances, namely, OP diesters that have a typical chemical structure of O = P(OR)(OH)). OP diesters are known as biotic or abiotic degradation products of OP triesters. In recent years, environmental scientists have proven that OP diesters widely exist in a variety of environmental matrices and biotic samples around the world, implying the potential risks from OP diester exposure to biota and humans in the environment. Here, we have reviewed the scientific literature for studies involving OP diesters and up to the end of 2020. The aim of the present review is to assess the present understanding of the physicochemical properties, sources (industrial production and degradation), environmental occurrence of OP diesters, and adverse effects to exposed organisms. Based on the literature in the Web of Science core collection, we found that at least 23 OP diesters have been reported as contaminants in various environments or as degradation products of OP triesters. The physicochemical properties of OP diesters vary depending on their specific chemical structures. OP diesters containing halogen atoms and aryl groups seem to be more persistent (with greater estimated half-life (t) values) in environmental matrices. There were multiple sources of OP diesters, including industrial production and biotic or abiotic degradation from OP triesters. Specifically, we found that ten OP diesters are produced somewhere in the world, and the total annual output was estimated to be 17,050 metric tons (this number is underestimated due to the limitation of the available information). In addition, the wide application of OP triesters worldwide makes the degradation of OP triesters another critical source of OP diesters to the environment and to organisms. Current monitoring studies have demonstrated that some OP diesters were detectable in the human body (via both blood and urine samples), indoor dust, wastewater, or sewage sludge worldwide. The highest concentrations of diphenyl phosphate (DPHP) in human urine have been reported as high as 727 ng/mL (children (aged 0-5 years) urine samples from Australia). In addition, adverse effects following direct or indirect exposure to 11 OP diesters in organisms (including animals, bacteria, and algae) have been reported, and the recorded adverse outcomes following exposure to OP diesters included developmental toxicity, alteration of gene expression, and disturbance of nuclear receptor activity. Biomonitoring studies regarding human samples have frequently reported statistically significant associations between the concentrations of OP diesters and markers of human health (mainly related to reproductive toxicity). Finally, on the basis of current knowledge on OP diesters, we propose prospects for related research directions in future studies.
Topics: Animals; Child; Dust; Environmental Monitoring; Esters; Flame Retardants; Humans; Organophosphates; Sewage; Wastewater
PubMed: 34146766
DOI: 10.1016/j.envint.2021.106691 -
Journal of Biomedical Materials Research Sep 2001A new bioactive bone cement, designated GBC, has been developed. It consists of polymethyl methacrylate (PMMA) as an organic matrix and bioactive glass beads as an...
A new bioactive bone cement, designated GBC, has been developed. It consists of polymethyl methacrylate (PMMA) as an organic matrix and bioactive glass beads as an inorganic filler. The bioactive beads, consisting of MgO--CaO--SiO(2)--P(2)O(5)--CaF(2) glass, have been newly designed, and a novel PMMA powder was selected. The purpose of the present study was to evaluate the effects on mechanical properties and osteoconductivity of adding a phosphoric ester (PE) monomer to the cement as an adhesion-promoting agent. Four kinds of cements were prepared: GBC, GBC with PE (designated GBC/PE), a cement consisting of the same PMMA used in GBC with apatite- and wollastonite-containing glass-ceramic (AW-GC) powder (designated AWC), and AWC with PE (designated AWC/PE). Each filler was added to the cement at 70 wt %. Adding PE to either GBC or AWC resulted in increases in the bending strength and decreases in the Young's modulus compared with the unmodified cements. Cements were packed into the intramedullar canals of rat tibiae to evaluate osteoconductivity as determined by an affinity index. Rats were sacrificed at 4 and 8 weeks after operation. The affinity index (length of bone in direct contact with the cement expressed as a percentage of the total length of the cement surface) was calculated for each cement. Adding PE to either GBC or AWC resulted in significant increases in the affinity index compared with the unmodified cements. The affinity index for GBC was significantly higher than that of AWC, and that for GBC/PE was also significantly higher than that of AWC/PE. The affinity indices for each cement increased significantly with time up to 8 weeks. Our study revealed that the higher osteoconductivity of GBC/PE was due to the large alkyl group in the PE monomer, to the hydrophilicity of the phosphoric acid in the PE monomer, and to the higher bioactivity of the bioactive glass beads at the cement surface. GBC/PE shows promise as an alternative bone cement with improved properties compared with conventional PMMA bone cement.
Topics: Animals; Bone Cements; Bone Remodeling; Male; Organophosphates; Rats; Rats, Wistar; Surface Properties
PubMed: 11400135
DOI: 10.1002/1097-4636(20010915)56:4<571::aid-jbm1129>3.0.co;2-h -
Biochimica Et Biophysica Acta Jan 2013The reactivity of triesters is discussed in the general context of phosphate transfer, as usually studied for the reactions of mono- and diesters. Systematic work has... (Review)
Review
The reactivity of triesters is discussed in the general context of phosphate transfer, as usually studied for the reactions of mono- and diesters. Systematic work has typically concentrated on the Linear Free Energy Relationships measuring the dependence of reactivity on the nucleophile and the leaving group, but new results indicate that it can depend equally strongly on the two non-leaving (sometimes known as spectator) groups. This conclusion is supported by first results from theoretical calculations: which also predict that a two-step mechanism can be favored over a concerted S(N)2(P) mechanism even for reactions involving leaving groups as good as p-nitrophenolate. This article is part of a Special Issue entitled: Chemistry and mechanism of phosphatases, diesterases and triesterases.
Topics: Models, Chemical; Organophosphates; Phosphates
PubMed: 22575086
DOI: 10.1016/j.bbapap.2012.04.010 -
Philosophical Transactions of the Royal... Jun 1981A general method has been developed for the synthesis of chiral [16O,17O,18O]phosphate monoesters of known absolute configuration. An analytic method for determining the... (Review)
Review
A general method has been developed for the synthesis of chiral [16O,17O,18O]phosphate monoesters of known absolute configuration. An analytic method for determining the absolute configuration of chiral phosphate esters has also been developed, which is based on the isotope effects of 17O and 18O at phosphorus in the 31P nuclear magnetic resonance spectrum. These methods have shown that phosphoryl transfer catalysed by hexokinase, phosphofructokinase and pyruvate kinase occurs with inversion of configuration. This is most simply interpreted as an "in-line' transfer of the phosphoryl group between substrates in the enzyme-substrate ternary complex.
Topics: Animals; Catalysis; Glycolysis; Hexokinase; Magnetic Resonance Spectroscopy; Organophosphates; Organophosphorus Compounds; Oxygen Isotopes; Phosphofructokinase-1; Phosphotransferases; Protein Conformation; Pyruvate Kinase; Stereoisomerism; Substrate Specificity
PubMed: 6115426
DOI: 10.1098/rstb.1981.0062 -
Zhonghua Yu Fang Yi Xue Za Zhi [Chinese... Oct 2020Organophosphate ester (OPEs) has been widely used as a substitute of brominated biphenyl ethers and other brominated flame retardant (BFRs), and their health effects and...
Organophosphate ester (OPEs) has been widely used as a substitute of brominated biphenyl ethers and other brominated flame retardant (BFRs), and their health effects and environmental impacts are widely concerned. This article systematically reviews the common types, metabolites, environmental occurrences, exposure pathways, levels, toxic effects and biomarkers of OPEs, in order to explore the relationships between OPEs exposures and biomarkers, to reveal the potential mechanisms of health effects, and to provide references and scientific basis for the health effects of OPEs exposure in China.
Topics: Biomarkers; China; Environmental Monitoring; Esters; Flame Retardants; Organophosphates
PubMed: 33115204
DOI: 10.3760/cma.j.cn112150-20200611-00868