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Primary and secondary kinetic and equilibrium isotope effects are calculated with density-functional methods for the dianionic methanolysis of the native (unsubstituted) and thio-substituted ethylene phosphates.
The tris(triphenylphosphine)copper(I) complexes [(PPh3)3CuX] for X = Cl (1), Br (2), I (3), ClO4 (4), BF4 (5), [(PPh3)3CuCl].CH3CN (1a), [Cu(PPh3)3(CH3CN)]X for X = ClO4 (6), BF4 (7), and [Cu(PPh3)3(CH3CN)]X.CH3CN for X = SiF5 (8), PF6 (9) have been studied by solid state 31P CP/MAS NMR spectroscopy together with single crystal X-ray diffraction for compounds (6)-(9), the latter completing the availability of crystal structure data for the series. Compounds (1)-(5) form an isomorphous series in space group P3 (a approximately 19, c approximately 11 A) with three independent molecules in the unit cell, all disposed about 3-fold symmetry axes. Average values (with estimated standard deviations) for the P-Cu-P, P-Cu-X bond angles and Cu-P bond lengths in compounds (1)-(3) are 110.1(6) degrees, 108.8(6) degrees and 2.354(8)A and 115.2(6) degrees, 102.8(9) degrees and 2.306(9)A for compounds (4) and (5). For the acetonitrile solvated compound (1a), the corresponding parameters are 115(4) degrees, 103(3) degrees and 2.309(3)A. The solid state 31P CP/MAS NMR quadrupole distortion parameters, dnu Cu, for (1)-(3) and (1a) are all less than 1 x 10(9) Hz2, despite the changes in donor properties of the halide in (1)-(3), and the coordination geometry of the P3CuX core in (1a). Change of anion to ClO4- and BF4- in compounds (4) and (5) results in a significant increase of dnu Cu to 4.4-5.2 10(9) Hz2 and 5.2-6.0 x 10(9) Hz2, respectively. Compounds (6) and (7) crystallise as isomorphous [Cu(PPh3)3(CH3CN)]X salts in space group Pbca, (a approximately 17.6, b approximately 22.3, c approximately 24.2 A), while compounds (8) and (9) crystallize as isomorphous acetonitrile solvated salts [Cu(PPh3)3(CH3CN)]X.CH3CN in space group P1(a approximately 10.5, b approximately 13.0, c approximately 19.5 A, alpha approximately 104, beta approximately 104, gamma approximately 94 degrees). The P3CuN angular geometries in all four compounds are distorted from tetrahedral symmetry with average P-Cu-P, P-Cu-N angles and Cu-P bond lengths of 115(4) degrees, 103(4) degrees and 2.32(1)A, with dnu Cu ranging between 1.3 and 2.5 x 10(9) Hz2. The solid state 29Si CP/MAS NMR spectrum of the pentafluorosilicate anion in compound (8) is also reported, affording 1J(29Si, 19F) = 146 Hz.
Organic extractants play a significant role in the selective removal of radioactive cations from waste streams. Although, literature on the selective removal of man-made radioactive material such as Americium (Am) is widespread, the selective removal of naturally occurring radioactive material such as Ra2+ is only mentioned sporadically. This tutorial review deals with the selective extraction of the highly radiotoxic Ra2+. Special attention is paid to different types of organic extractants used.
The borane complexes cyclo-1,4-(BH3)2(P4Ph4CH2) (3) and cyclo-1,2-(BH3)2(P5Ph5) (4) were prepared by reaction of cyclo-(P4Ph4CH2) and cyclo-(P5Ph5) with BH3(SMe2). Only the 2:1 complexes 3 and 4 were isolated, even when an excess of the borane source was used. In solution, 3 exists as a mixture of the two diastereomers (R(P)*,S(P)*,S(P)*,R(P)*)-(+/-)-3 and (R(P)*,R(P)*,R(P)*,R(P)*)-(+/-)-3. However, in the solid state the (R(P)*,S(P)*,S(P)*,R(P)*)-(+/-) diastereomer is the major stereoisomer. Similarly, while only one isomer of 4 is observed in its X-ray structure, NMR spectroscopic investigations reveal that it forms a complex mixture of isomers in solution. 3 may be deprotonated with tBuLi to give the lithium salt cyclo-1,4-(BH3)2(P4Ph4CHLi) (3 x Li), though this could not be isolated in pure form.
The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.
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1. A critical study was made of the quantitative extraction of nucleotide and sugar phosphates from plant tissue by either boiling aqueous ethanol or cold trichloroacetic acid. The effect of the extraction technique on the inactivation of the enzymes in the plant tissue and the possibility of adsorption of the phosphate esters on the cell wall were especially considered. 2. In the recommended method the plant tissue was frozen in liquid nitrogen, ground to a powder and then blended with cold aqueous trichloroacetic acid containing 8-hydroxyquinoline to prevent adsorption. 3. The extract contained large amounts of trichloroacetic acid, cations, chloride, sugars, amino acids, hydroxy organic acids, phytic acid, orthophosphoric acid and high-molecular-weight material including some phosphorus-containing compounds. All of these were removed as they were liable to interfere with the chromatographic or enzymic assay of the individual nucleotide or sugar phosphates. 4. The procedure was as follows: the last traces of trichloroacetic acid were extracted with ether after the solution had been passed through a column of Dowex AG 50 in the hydrogen form to remove all cations. High-molecular-weight compounds were removed by ultrafiltration and low-molecular-weight solutes by a two-stage chromatography on cellulose columns with organic solvents. In the first stage, sugars, amino acids, chloride and phytic acid were separated by using a basic solvent (propan-1-ol-water-aqueous ammonia) and, in the second stage, the organic acids and orthophosphoric acid were separated by using an acidic solvent (di-isopropyl ether-formic acid-2-methylpropan-2-ol-water). The final solution of nucleotide and sugar phosphates was substantially free from other solutes and was suitable for the detection of individual phosphate esters by either chromatography or enzymic assay. 5. The recovery of d-glucose 6-phosphate or adenosine 5'-triphosphate added to a trichloroacetic acid extract simulating that from peas and potatoes, and isolated according to the standard procedures, was better than 95%. Estimation of naturally occurring d-glucose 6-phosphate and adenosine 5'-triphosphate in the initial extract of peas and potatoes and in the final purified extract also indicated a recovery of about 95%. A similar estimation of uridine diphosphate glucose in potatoes showed that little or no breakdown occurred.
1. Patients with a history of alcohol abuse were studied by 31P n.m.r. spectroscopy of the liver in vivo, and the results were related to the pattern of disease assessed by standard biochemical and histological techniques. 2. The ratios of metabolites measured from the 31P n.m.r. spectra were abnormal in patients with alcoholic hepatitis but not in those with fatty change or cirrhosis in the absence of hepatitis. In particular, the levels of phosphomonoesters were raised, with respect either to Pi, or to adenosine 5'-triphosphate. The level of phosphomonoesters showed a significant positive correlation with the severity of alcoholic hepatitis, assessed by histology. 3. The ratio of Pi to adenosine 5'-triphosphate was used as a measure of the energy status of the hepatocytes, and was unchanged between patients and controls.
Electron energy-loss spectroscopic imaging (ESI) yields high-resolution, element-sensitive images. However, ESI suffers from difficulties in distinguishing element-specific and background contributions. New methods have therefore been introduced which use grey-level measurements in micrographic images for a more accurate detection of element distributions. A videodensitometric method allowed the detection of low phosphorus levels in axoplasmic neurofilaments of squid giant axons. Here we further verify these results by investigating the relationship of videodensitometry and electron energy-loss spectroscopy (EELS), particularly considering the peculiarities of these methods in terms of automatic background correction and representation of the results. Six biological specimens and two nonbiological specimens were examined both by EELS and by videodensitometry. In all cases comparable results were obtained. The overlapping PL2,3 and SL2,3 ionization edges could clearly be recognized individually by both methods, and controls showed that mass density variations within the specimens did not impair elemental analysis. Additional evidence supporting the detection of phosphorylation sites in squid neurofilaments was obtained in both EELS and videodensitometric measurements of neurofilament-enriched pellets and of aggregated axoplasmic particles. Thus, video-densitometry appears to be a useful tool for an improved exploration of the full imaging capabilities of energy filtering electron microscopy.
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The abortive development of bacteriophage T7 in E. coli cells carrying F factors has previously been attributed to a lack of virus-directed modification of ribosomes in such cells. We find it unnecessary to postulate such translational control to explain the failure of T7 development. Instead, there is a general cessation of macromolecular syntheses around 8 min after T7 infection of F' cells. This cessation is correlated with a sudden outflow of the entire acid-soluble pool of phosphorus-containing compounds and loss of the ability to accumulate amino acids. Manifestation of these defects requires expression of at least one T7 gene and one episomal gene.
Protein-tyrosine phosphatases (PTPs) are critically involved in regulation of signal transduction processes. Members of this class of enzymes are considered attractive therapeutic targets in several disease states, e.g. diabetes, cancer, and inflammation. However, most reported PTP inhibitors have been phosphorus-containing compounds, tight binding inhibitors, and/or inhibitors that covalently modify the enzymes. We therefore embarked on identifying a general, reversible, competitive PTP inhibitor that could be used as a common scaffold for lead optimization for specific PTPs. We here report the identification of 2-(oxalylamino)-benzoic acid (OBA) as a classical competitive inhibitor of several PTPs. X-ray crystallography of PTP1B complexed with OBA and related non-phosphate low molecular weight derivatives reveals that the binding mode of these molecules to a large extent mimics that of the natural substrate including hydrogen bonding to the PTP signature motif. In addition, binding of OBA to the active site of PTP1B creates a unique arrangement involving Asp(181), Lys(120), and Tyr(46). PTP inhibitors are essential tools in elucidating the biological function of specific PTPs and they may eventually be developed into selective drug candidates. The unique enzyme kinetic features and the low molecular weight of OBA makes it an ideal starting point for further optimization.
Genes associated with Parkinson's disease (PD) have suggested a role for ubiquitin-proteasome dysfunction and aberrant protein degradation in this disorder. Inasmuch as oxidative stress has also been implicated in PD, the present study examined transcriptional changes mediated by the Parkinsonism-inducing neurotoxins 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP+) in a dopaminergic cell line. Microarray analysis of RNA isolated from toxin treated samples revealed that the stress-induced transcription factor CHOP/Gadd153 was dramatically up-regulated by both 6-OHDA and MPP+. Treatment with 6-OHDA also induced a large number of genes involved in endoplasmic reticulum stress and unfolded protein response (UPR) such as ER chaperones and elements of the ubiquitin-proteasome system. Reverse transcription-PCR, Western blotting, and immunocytochemical approaches were used to quantify and temporally order the UPR pathways involved in neurotoxin-induced cell death. 6-OHDA, but not MPP+, significantly increased hallmarks of UPR such as BiP, c-Jun, and processed Xbp1 mRNA. Both toxins increased the phosphorylation of UPR proteins, PERK and eIF2 alpha, but only 6-OHDA increased phosphorylation of c-Jun. Thus, 6-OHDA is capable of triggering multiple pathways associated with UPR, whereas MPP+ exhibits a more restricted response. The involvement of UPR in these widely used neurotoxin models supports the role of ubiquitin-proteasome pathway dysfunction in PD.
Using Propionibacterium freudenreichii and 32P-ATP, batches of 32P-labelled cobalamin (Cbl) were biosynthesized with a maximum specific activity of 61 microCi/mg, i.e. about 100 times higher than previously reported. Pharmacological doses mixed with 57Co-Cbl were injected subcutaneously in the form of hydroxo-Cbl into rats subsequently killed 5-20 days later. The two labelled Cbls were distributed in approximately the same way, the highest concentration being found in kidney (typical for rats) and about one-fifth of that in liver. These findings tallied with previous observations with radioactive cyano-Cbl and microbiological assay. In all injected rats, the 57Co/32P ratio was lower in liver than in kidney. Drugs eradicating the intestinal flora had no influence. In rats receiving the vitamin orally, the ratio was higher in liver than in kidney. All of our findings could be due to formation of a cobinamide-like compound lacking phosphorus. It is concluded that we have produced radiophosphorus-labelled Cbl that enables studies in vivo.
In this study, we evaluated the effect of the application by two agrochemicals, methamidophos (O,S-dimethyl phosphoroamidothioate) and urea, on microbial diversity in soil, using the combined approaches of soil microbial biomass analysis and community level physiological profiles (CLPPs). The results showed that both a low and a high level of methamidophos application (CS2 and CS3) and urea application (CS4) significantly decreased microbial biomass C (Cmic) by 41-83% compared with the control (CS1). The soil organic C (Corg) values of CS3 and CS4 were significantly higher and lower by 24% and 14%, respectively, than that of CS1. Similarly to Cmic, the values of Cmic/Corg of the three applied soils which decreased were lower by 31-84% than that of CS1. In contrast, the respiration activity of the three applied soils were significantly higher than the control. Agrochemical application also significantly increased the soil total of N and P (Ntol and Ptol) and decreased the Corg/Ntol and Corg/Ptol values. The CLPPs results showed that the AWCD (average well color development) of the three applied soils were significantly higher than that of CS1 during the incubation period. Substrate richness, Shannon and Simpson indices of microbial communities under chemical stresses, increased significantly. In addition, the CFU (colony-forming unit) numbers of methamidophos metabolized bacteria in CS2 and CS3 also increased significantly by 86.1% and 188.9% compared with that of CS1. The combined results suggest that agrochemicals reduce microbial biomass and enhance functional diversities of soil microbial communities; meanwhile, some species of bacteria may be enriched in soils under methamidophos stress.
Movement and Metabolism of 32P and 35S-double labeled Kitazin P (S-benzyl O,O-diisopropyl phosphorothiolate) and 35S-labeled edifenphos (O-ethyl S,S-diphenyl phosphorodithiolate) were examined with three types of soils, sandy loam, alluvial clay loam, and volcanic ash loam. Vertical movement of both the compounds in soil column was different with soil types, and the order of mobility in soil column was as follows: sandy loam greater than alluvial clay loam greater than volcanic ash loam. Persistence of edifenphos in soil was shorter than that of Kitazin P. Main degradation products at the initial stage of metabolism were S,S,S-triphenyl phosphorotrithiolate, O,O-diethyl S-phenyl phosphorothiolate, S-phenyl dihydrogen phosphorothiolate and diphenyl disulfide in edifenphos and O,O-diisopropyl hydorgen phosphorothioate in Kitazin P. Sulfur atom of Kitazin P was found in sulfuric acid at a minor level through dibenzyl disulfide and toluene-alpha-sulfonic acid, and that of edifenphos was converted to sulfuric acid through diphenyl disulfide and benzenesulfonic acid. Kitazin P under flooded condition of alluvial clay loam was slightly more persistent as compared with upland condition. Sterilized condition of Kitazin P did not cause any appreciable degradation throughout the experimental period, but such condition did not necessarily prevent the degradation of edifenphos.
Thymine and 2',3',5'-tri-O-acetyl-psi-uridine (1) was converted into the corresponding 2,4-ditriazolyl derivatives 5 and 2, respectively. Of these two substituents, the C4-triazolyl group was found to be quite susceptible to nucleophilic substitution while the other triazolyl is resistant.
Six novel artificial ribonucleases were synthesized employing a stereochemically pure abasic serinol backbone residue for attachment of the RNA transesterification agent copper(II) terpyridine. These stereochemically pure abasic residues were synthesized as phosphoramidite building blocks from the parent L-serine and D-serine starting building blocks and incorporated into oligonucleotides via solid-phase DNA synthesis. These artificial ribonucleases were constructed to determine if the stereochemistry of the alpha carbon of an abasic serinol residue has influence over RNA transesterification through selective placement of a pendant transesterification agent in either the major or minor groove. The novel artificial ribonucleases and previously synthesized artificial ribonucleases were challenged with a 28-mer and 159-mer RNA substrate. It was determined that the stereochemistry of the carbon atom derived from the alpha-carbon of serine did not influence the extent of cleavage in these studies using copper(II) terpyridine conjugated artificial ribonucleases.