Water-soluble Phosphate Research Articles

A film of collagen/calcium phosphate composite prepared by enzymatic mineralization in an aqueous phase

Collagen/calcium phosphate composite materials were prepared using an alkaline phosphatase-catalyzed hydrolysis of water-soluble phosphate esters in the presence of calcium ions. We prepared a collagen/calcium phosphate composite film by adding sequentially calcium chloride, disodium glycerophosphate and alkaline phosphatase to collagen solution and subsequent drying of the resultant composite suspension in a template. The calcium phosphate contained in the film was determined to be mainly hydroxyapatite from FT-IR and X-ray diffraction analysis. The film little swelled in water to keep its original morphology, while a collagen film became solubilized. This suggests the binding between collagen and calcium phosphate in complex materials. When the preosteoblast cell line, MC3T3-E1 cells were cultured on the film, the film was found to support the osteoblastic differentiation from the measurement of alkaline phosphatase activity, which is an early differentiation marker.

The nitroreductase prodrug SN 28343 enhances the potency of systemically administered armed oncolytic adenovirus ONYX-411NTR

Conditionally replicating adenoviruses (CRAd) 'armed' with prodrug-activating genes have the potential to augment the efficacy of virotherapy. An Escherichia coli nitroreductase (NTR) gene (nfsB) was introduced into the E3B region of the systemically active CRAd ONYX-411, to produce ONYX-411(NTR), which had single agent oncolytic activity equivalent to unarmed virus in vitro and in vivo. A fluorogenic probe (SN 29884) developed to monitor NTR expression revealed robust, durable NTR expression in ONYX-411(NTR) infected neoplastic but not primary human cell lines. NTR expression occurred >24 h post-infection in parallel with fiber and was sensitive to ara-C indicating transcriptional linkage to viral replication. A novel NTR prodrug, the 3,5-dinitrobenzamide-2-bromomustard SN 27686, was shown to be more dose potent and selective than CB 1954 and provided a superior bystander effect in 3D multicellular layer cultures. Its water-soluble phosphate ester SN 28343 was substantially more active than CB 1954 against xenografts containing a minority of stable NTR-expressing cells. A single intravenous dose of ONYX-411(NTR) (10(8) PFU) to nude mice bearing large H1299 xenografts (>350 mm(3)) resulted in tumor-specific NTR expression which increased over time. Despite extensive viral spread by day 14, this conservative virus dose and schedule was unable to control such well-established tumors. However, subsequent administration of SN 28343 resulted in the majority of mice (62.5%) being tumor-free on day 120.

Abstracts of Nippon Dojo-Hiryogaku Zasshi

Abstracts of Nippon Dojo-Hiryogaku Zasshi

Release of phosphorous from igneous phosphate rock through bioturbation: a low-cost approach for phosphorous fertilization in fish farms

The influence of bioturbation caused by common carp fry was treated in 24 transparent polythene jars (5 L each) in the laboratory and in outdoor vats (150 L), increasing the fertilizer value of phosphate rock in eight treatment combinations in triplicate. Input of water soluble reactive phosphate (SRP) was determined to quantify the effects of bioturbation, fish excrements and soil. The level of SRP in water was always lowest in the control series. Introduction of common carp fry resulted in a net increase of 0.009–0.010 mg phosphate g−1day−1 of SRP attributable to the effect of fish excrement. Bioturbation caused by common carp resulted in as high as a 64.8 to 90% influx of phosphate from bottom soil in the presence of phosphate rock but only about 6.3 to 7.2% in the absence of phosphate rock. The bioturbation that occurred in this treatment resulted in a significant release of phosphorous into the overlying water from an apatite source. The results confirm the environment friendly application of phosphate rock in fish-farming ponds at low cost.

Identification of human reductases that activate the dinitrobenzamide mustard prodrug PR-104A: A role for NADPH:cytochrome P450 oxidoreductase under hypoxia

Hypoxia is a common trait found in many solid tumours and thus represents a therapeutic target with considerable potential. PR-104, a hypoxia-activated prodrug currently in clinical trial, is a water-soluble phosphate ester which is converted in vivo to the corresponding alcohol, PR-104A. This 3,5-dinitrobenzamide-2-nitrogen mustard is activated by reduction to the corresponding 5-hydroxylamine (PR-104H) and 5-amine (PR-104M) in hypoxic cells. The clinical effectiveness of PR-104 will depend in part on the expression of reductases within tumours that can effect this reduction. Here, we evaluate the roles of NADPH:cytochrome P450 oxidoreductase (CYPOR; E.C.1.6.2.4) and NAD(P)H:quinone oxidoreductase (NQO1; E.C.1.6.99.2) as candidate PR-104A reductases. A weak correlation was observed between NQO1 activity and aerobic cytotoxicity in a panel of eight tumour cell lines. However, overexpression of human NQO1 did not increase cytotoxicity of PR-104A or the formation of PR-104H/M, showing that PR-104A is not a substrate for NQO1. Overexpression of human CYPOR did, however, increase the hypoxic cytotoxicity of PR-104A, and its metabolism to PR-104H and PR-104M, demonstrating it to be a PR-104A reductase. To assess the contribution of CYPOR to overall activation of PR-104A in hypoxic SiHa cells, a combination of siRNA transfection and antisense expression were used to suppress CYPOR protein by 91% (±3%), a phenotype which conferred 45% (±7%) decrease in cytotoxic potency of PR-104A. Regression analysis of all CYPOR depletion data was found to correlate with cytoprotection and metabolism ( p < 0.001). Residual PR-104A reductase activity could be inhibited by the flavoprotein inhibitor diphenyliodonium. We conclude that CYPOR is an important PR-104A reductase, but that other flavoenzymes also contribute to its activation in hypoxic SiHa cells.

Nucleoside Phosphorylation by Phosphate Minerals

In the presence of formamide, crystal phosphate minerals may act as phosphate donors to nucleosides, yielding both 5'- and, to a lesser extent, 3'-phosphorylated forms. With the mineral Libethenite the formation of 5'-AMP can be as high as 6% of the adenosine input and last for at least 10(3) h. At high concentrations, soluble non-mineral phosphate donors (KH(2)PO(4) or 5'-CMP) afford 2'- and 2':3'-cyclic AMP in addition to 5'-and 3'-AMP. The phosphate minerals analyzed were Herderite Ca[BePO(4)F], Hureaulite Mn(2+)(5)(PO(3)(OH)(2)(PO(4))(2)(H(2)O)(4), Libethenite Cu(2+)(2)(PO(4))(OH), Pyromorphite Pb(5)(PO(4))(3)Cl, Turquoise Cu(2+)Al(6)(PO(4))(4)(OH)(8)(H(2)O)(4), Fluorapatite Ca(5)(PO(4))(3)F, Hydroxylapatite Ca(5)(PO(4))(3)OH, Vivianite Fe(2+)(3)(PO(4))(2)(H(2)O)(8), Cornetite Cu(2+)(3)(PO(4))(OH)(3), Pseudomalachite Cu(2+)(5)(PO(4))(2)(OH)(4), Reichenbachite Cu(2+)(5)(PO(4))(2)(OH)(4), and Ludjibaite Cu(2+)(5)(PO(4))(2)(OH)(4)). Based on their behavior in the formamide-driven nucleoside phosphorylation reaction, these minerals can be characterized as: 1) inactive, 2) low level phosphorylating agents, or 3) active phosphorylating agents. Instances were detected (Libethenite and Hydroxylapatite) in which phosphorylation occurs on the mineral surface, followed by release of the phosphorylated compounds. Libethenite and Cornetite markedly protect the beta-glycosidic bond. Thus, activated nucleic monomers can form in a liquid non-aqueous environment in conditions compatible with the thermodynamics of polymerization, providing a solution to the standard-state Gibbs free energy change (DeltaG degrees ') problem, the major obstacle for polymerizations in the liquid phase in plausible prebiotic scenarios.

Manipulating mechanics and chemistry in precision optics finishing

abstractDeterministic processing is critical to modern precision optics finishing. Put simply, determinism is the ability to predict an outcome before carrying out an activity. With the availability of computer numerically controlled (CNC) equipment and sophisticated software algorithms, it is now possible to grind and polish optics from a variety of materials to surface shape accuracies of ∼20 nm peak-to-valley (p–v), with surface roughness values (measured on white light interferometers over 250 μm 350 μm areas) to sub-nm root-mean-square (rms) levels. In the grinding phase the capability now exists to estimate removal rates, surface roughness, and the depth of subsurface damage (SSD) for a previously unprocessed material, knowing its Young’s modulus, hardness, and fracture toughness. An understanding of how chemistry aids in the abrasive-driven removal of material from the surface during polishing is also critical. Recent polishing process research reveals the importance of chemistry, specifically slurry pH, for preventing particle agglomeration in order to achieve smooth surface finishes with conventional pad or pitch laps. New sub-aperture polishing processes like magnetorheological finishing (MRF) can smooth and shape flat, spherical, aspheric and free-form surfaces within a few process iterations. Difficult to finish optical materials like soft polymer polymethyl methacrylate, microstructured polycrystalline zinc sulfide, and water soluble single-crystal potassium dihydrogen phosphate (KDP) can be finished with MRF. The key is the systematic alteration of MR fluid chemistry and mechanics (i.e. the abrasive) to match the unique physical properties of each workpiece.

Efficacy of soluble sodium tripolyphosphate amendments for the in-situ immobilisation of uranium

Environmental context. Contamination of groundwater and sediments by heavy metals and radioactive metals is a significant problem within the United States Department of Energy complex as a result of past nuclear operations. One way to remediate these metals is through reaction with phosphate compounds, which can immobilise the metals by forming highly stable metal phosphate compounds. Long-chain, water-soluble phosphate compounds provide a means to inject phosphate into subsurface contaminant plumes, to precipitate metal ions from solution. Results presented here illustrate that application of a soluble sodium tripolyphosphate to sediment contaminated with uranium will rapidly reduce the concentration of uranium in the pore water to concentrations near or below drinking water limits under water-saturated and unsaturated conditions. Abstract. A series of conventional water-saturated and pressurised unsaturated flow column experiments were conducted to evaluate the effects of using soluble polyphosphate amendments for in-situ, subsurface remediation of uranium. Experiments were conducted under mildly alkaline, calcareous conditions, representative of conditions commonly encountered at sites across the arid western United States. Results presented here illustrate that application of a soluble polyphosphate amendment to sediment contaminated with uranium will rapidly reduce the concentration of uranium released to the porewater to near or below drinking water limits under water-saturated and -unsaturated conditions. Column experiments conducted in the absence of polyphosphate illustrate sustained release of aqueous uranium at concentrations well above drinking water standards in excess of over 25 pore volumes under water-saturated conditions and over 50 pore volumes under unsaturated conditions. In the presence of tripolyphosphate, the concentration of aqueous uranium released from the sediment was below drinking water limits within 10 to 35 pore volumes under water-saturated and unsaturated conditions, respectively. Moreover, results indicate the necessity of conducting site-specific dynamic tests to tailor phosphate-based remediation technology to site specific geochemical and hydrological conditions.

Reducing phosphorus release from paddy soils by a fly ash-gypsum mixture

A mixture of fly ash and phospho-gypsum (50:50, wt wt −1) was selected to study its potential to supply Ca and Si to rice while reducing B toxicity. We expected that the high Ca content in this mixture might convert water-soluble P to less soluble forms and thereby reduce the loss of soil P to surface runoff. The mixture was applied at rates of 0, 20, 40, and 60 Mg ha −1 in two paddy soils of contrasting textures (silt loam in Yehari and loamy sand in Daegok). The mixture significantly reduced water-soluble phosphate (W-P) in the surface soils by shifting from W-P and iron bound-P (Fe-P) to calcium bound-P (Ca-P) and aluminum bound-P (Al-P) during rice cultivation in both soils. Lancaster and Mehlich 3 extractable P increased significantly with application rate due to high contents of P and Si in the mixture. Mixtures of fly ash and phospho-gypsum should reduce P loss from rice paddy soils and increase soil fertility.

Improving Potency, Selectivity, and Water Solubility of Adenosine A1 Receptor Antagonists: Xanthines Modified at Position 3 and Related Pyrimido[1,2,3‐cd]purinediones

The structure-activity relationships of xanthine derivatives related to the adenosine A(1) receptor antagonists 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and 1,3-dipropyl-8-(3-noradamantyl)xanthine (KW3902) were investigated by focusing on variations of the 3-substituent. Aromatic residues were well tolerated by the A(1) receptor in that position. A moderate effect of stereochemistry was found for the 3-(1-phenylethyl)-substituted analogue of DPCPX (S>R) at A(1) and A(3) receptors, whereas the opposite stereoselectivity was observed at the A(2) receptor subtypes. A 3-hydroxypropyl substituent was found to be optimal for high A(1) affinity and selectivity. The most potent compound of the present series was 1-butyl-3-(3-hydroxypropyl)-8-(3-noradamantyl)xanthine (10 c), which exhibits a K(i) value of 0.124 nM at rat, and 0.7 nM at human adenosine A(1) receptors, combined with high selectivity (>>200-fold) versus the other receptor subtypes. The similarly potent 8-cyclopentyl-3-(3-hydroxypropyl)-1-propylxanthine was converted into a water-soluble phosphate prodrug, which may become a useful pharmacological tool for in vivo studies. 8-Alkyl-2-(3-noradamantyl)pyrimido[1,2,3-cd]purine-8,10-diones, which can be envisaged as xanthine analogues with a fixed 3-propyl substituent, were identified as a new class of potent, selective adenosine A(1) receptor antagonists. For example, compound 14 (8-butyl-substituted) exhibits a K(i) value of 13.8 nM at human A(1) receptors. A selection of the most potent compounds was investigated in [(35)S]GTPgammaS binding assays and showed inverse agonistic activity. Their efficacy was generally lower than that of the full inverse agonist DPCPX, and depended on subtle structural changes. Some of the new compounds belong to the most potent and selective A(1) antagonists described to date.

Evaluation of phosphate fertilizers for ameliorating acid mine waste

The aim of the study was to determine whether the application of bulk industrial chemicals (potassium permanganate and water-soluble phosphate fertilizer) to partly oxidized, polyminerallic mine wastes can inhibit sulfide oxidation, and metal and metalloid mobility. The acid producing waste rocks were metal (Pb, Zn, Cu) and metalloid (As, Sb) rich and consisted of major quartz, dickite, illite, and sulfide minerals (e.g., galena, chalcopyrite, tetrahedrite, sphalerite, pyrite, arsenopyrite), as well as minor to trace amounts of pre- and post-mining oxidation products (e.g., hydrated Fe, Cu, Pb, and alkali mineral salts). SEM-EDS observations of treated waste material showed that metal, metal–alkali, and alkali phosphate coatings developed on all sulfides. The abundance of phosphate phases was dependant on the fertilizer type and the availability of metal and alkali cations in solution. In turn, the release of cations was dependent on the amount of sulfide oxidation induced by KMnO 4 during the experiment and the dissolution of soluble sulfates. Mn, Ca, Fe, and Pb phosphates remained stable during H 2O 2 leaching, preventing acid generation and metal release. In contrast, the lack of complete phosphate coating on arsenopyrite allowed oxidation and leaching of As to proceed. The mobilized As did not form phosphate phases and consequently, As displayed the greatest release from the coated waste. Thus, the application of KMnO 4 and the water-soluble phosphate fertilizer Trifos (Ca(H 2PO 4) 2) to partly oxidized, polyminerallic mine wastes suppresses sulfide oxidation and is most effective in inhibiting Cu, Pb, and Zn (Sb) release. However, the technique appears ineffective in suppressing oxidation of arsenopyrite and preventing As leaching.

Phosphorus Availability in Soils Amended with Different Phosphate Fertilizers

Accurate measurement and characterization of phosphate rock dissolution are important for a better understanding of phosphorus (P) availability in soils. An incubation study was carried out on two New Zealand topsoils (0–15 cm; high P buffering capacity Craigieburn and low P buffering capacity Templeton) amended with North Carolina phosphate rock (NCPR) and water‐soluble phosphate (WSP) at 218 mg P kg−1 (equivalent to 60 kg P ha−1). Isotopic exchange kinetics was carried out after 12 h and 28 days of incubation to characterize P availability. This study showed that sensitivity of capacity factors (r1/R, n) to explain changes in E1min values was affected by the P buffering capacity of the soils. The recovery of applied P in the E pool (RecinE%) with extended incubation time was similar from the NCPR and WSP treatments (3.1–3.3%) in the Craigieburn soil compared with the Templeton soil in which RecinE% values were greater in WSP (9%) than NCPR (1.3%) treatment. The higher values of P derived from the applied P fertilizers in the E pool (PdffinE%>80%) suggested that the NCPR application in both soils would be efficient for increasing P availability to plants.

Comparative Analysis of Soluble Phosphate Amendments for the Remediation of Heavy Metal Contaminants: Effect on Sediment Hydraulic Conductivity

Environmental Context. The contamination of surface and subsurface geologic media by heavy metals and radionuclides is a significant problem within the United States Department of Energy complex as a result of past nuclear operations. Water-soluble phosphate compounds provide a means to inject phosphorus into subsurface contaminant plumes, to precipitate metal ions from solution. However, phosphate phases can form within the sedimentary pore structure to block a fraction of the pore space and inhibit further remediation of the contaminant plume. A series of tests have been conducted to evaluate changes in sedimentary pore structure during the application of several proposed phosphate remediation amendments. Abstract. A series of conventional, saturated column experiments have been conducted to evaluate the effect of utilizing in situ, soluble, phosphate amendments for subsurface metal remediation on sediment hydraulic conductivity. Experiments have been conducted under mildly alkaline and calcareous conditions representative of conditions commonly encountered at sites across the arid western United States, which have been used in weapons and fuel production and display significant subsurface contamination. Results indicate that the displacement of a single pore volume of either sodium monophosphate or phytic acid amendments causes approximately a 30% decrease in the hydraulic conductivity of the sediment. Long-chain polyphosphate amendments afford no measurable reduction in hydraulic conductivity. These results demonstrate (1) the efficacy of long-chain polyphosphate amendments for subsurface metal sequestration; and (2) the necessity of conducting dynamic experiments to evaluate the effects of subsurface remediation.

Zur Phosphatfixierung in sächsischen Verwitterungsböden auf den Ergussgesteinen Nephelinbasalt, Phonolith und Diabas

Investigated Saxonic brown soils (Cambisols) on nephelinbasalt, phonolith and diabase in a considerable extent are able to remove water soluble phosphate to a form, which is not double lactate soluble and not available for plants. With regard to this property these soils show a strong phosphate fixation. However, measure of phosphate fixation of soils–ratio of hydrochloric acid soluble phosphorus (P-HCl) and double lactate soluble phosphorus (P-DL) – is different depending on specific weathering rock. Soils on nephelinbasalt are marked by very high ratios and reach values of 36 to 166. They distinguish from soil on phonolith with ratio 15 and soils on diabase with ratios in the range of 9 – 21. Differences between intensities of phosphate fixation possibly can be caused by different mineralogical compositions of weathering rocks and soils and their specific ability of weathering depending on their crystal structure and resulting in different intensities of weathering by soil minerals. Correlation between phosphate fixation and intensities of weathering by soil minerals especially is demonstrated by soils on nephelinbasalt showing strong phosphate fixation and simultaneously higher contents of weathering products of oxalate and dithionite soluble iron and “free” aluminium (by Foster). For minimizing phosphate fixation, arable soils should be regulated to optimal pH and manuring of phosphate should be given each year and, if possible, nearby the roots of plants.

Polishing slurry induced surface haze on phosphate laser glasses

The effects of residual polishing slurry on the surface topology of highly polished, Nd-doped meta-phosphate laser glasses are reported. Glass samples were pitched polished using cerium oxide or zirconium oxide slurry at different pHs and then washed by different methods that allowed varying amounts of residual slurry to ‘dry’ on the surface. Upon rewashing with water, some of the samples showed surface haze (scatter), which scaled with the amount of residual slurry. Profilometry measurements showed that the haze is the result of shallow surface pits (100 nm–20 μm wide × ∼15 nm deep). Chemical analyses of material removed during rewashing, confirmed the removal of glass components as well as the preferential removal of modifier ions (e.g., K 1+ and Mg 2+). The surface pits appear to result from reaction of the glass with condensed liquid at the slurry particle–glass interface that produces water-soluble phosphate products that dissolves away with subsequent water contact. Aggressive washing, to remove residual slurry immediately following polishing, can minimize surface haze on phosphate glasses. It is desirable to eliminate haze from glass used in high-peak-power lasers, since it can cause scatter-induced optical modulation that can cause damage to downstream optics.

Synthesis and in vitro Antitumor Activity of Substituted Anthracene‐1,4‐diones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis and in vitro antitumor activity of substituted anthracene-1,4-diones

Based on a rational approach, 6-substituted 1,4-anthracenediones were synthesized and found to exhibit potent cytotoxic activity against murine and human leukemic cells. The synthetic sequence includes a double Friedel–Crafts reaction, reductive quinone formation, and selective bromination of the alkyl side chain. A key intermediate, 6-bromomethyl-1,4-anthracenedione ( 10 ), was synthesized and converted to various active antitumor agents, including a water-soluble phosphate ester pro-drug. The interconversion reactions include displacement of the bromide with various nucleophiles and basic hydrolysis to the alcohol and subsequent oxidation to provide the aldehyde. Based on their ability to decrease L1210 and HL-60 tumor cell viability, 1,4-dihydroxyanthraquinones are inactive but 1,4-anthracenediones have interesting antitumor activity, which may be abolished by modification of the A-ring and improved by substitution of the C-ring. The cytostatic and cytotoxic activity of the representative compound 10 was verified at the National Cancer Institute in studies on the 60-human tumor cell line panel in the in vitro antitumor screening. A wide spectrum of tumor cells are sensitive to 10 inhibition, and concentrations required to inhibit tumor cell growth by 50% (GI 50) at 48 h are <10 nM in HL-60 and MOLT-4 and 37.1 nM in SR leukemia. Preliminary studies suggest that the molecular targets and mechanisms of action of 10 may be different from those of daunomycin.

496 Water-soluble dinitrobenzamide mustard phosphate pre-prodrugs as hypoxic cytotoxins

496 Water-soluble dinitrobenzamide mustard phosphate pre-prodrugs as hypoxic cytotoxins

Design, synthesis and in vitro evaluation of novel water-soluble prodrugs of buparvaquone.

Novel water-soluble phosphate prodrugs (2b-5b) of buparvaquone-oxime (1a) and buparvaquone-O-methyloxime (1b) were synthesized and evaluated in vitro as potential oral prodrugs against leishmaniasis. Buparvaquone-oxime (1a), and most probably also buparvaquone-O-methyloxime (1b), released the parent buparvaquone via a cytochrome P450-catalysed reaction. The prodrugs 2b-5b showed significantly higher aqueous solubilities (>4 mg/ml) than buparvaquone (< or = 0.03 microg/ml) over a pH range of 3.0-7.4. The prodrugs 2b, 3b and 5b rapidly released (t1/2 = 7 min) the corresponding oximes of buparvaquone (1a and 1b), and prodrug 4b at a moderate rate (t1/2 = 22.5 min) in alkaline phosphatase solution in vitro. Prodrug 3b was the most chemically stable in the aqueous solutions over a pH range of 3.0-7.4 (t1/2 > 8 days). Although buparvaquone-oxime (1a) has been shown to undergo a cytochrome P450-catalysed oxidation in liver microsomes to the parent buparvaquone and behave as a novel bioreversible prodrug, its usefulness is limited in oral drug delivery due to its poor aqueous solubility, like buparvaquone itself. Further phosphorylation of an oxime form of buparvaquone significantly increased water solubility, and this novel approach is therefore useful to improve physicochemical properties of drugs containing a ketone functional group.

Preparation of collagen/calcium phosphate multilayer sheet using enzymatic mineralization

The multilayer sheets (2–10 layers), which consisted of alternately cumulated collagen and calcium phosphate layers with the thickness of 6–8 μm in each layer, were prepared. The inorganic layer was mineralized by means of an alkaline phosphatase-catalyzed hydrolysis of water-soluble phosphate esters in the presence of calcium ions. The calcium phosphate, which was formed on the collagen, was assayed as a mixture of hydroxyapatite (main) and amorphous calcium phosphate. The multilayer sheets were not only strong mechanically but also semitransparent and flexible in a dry state. Furthermore, the collagen/calcium phosphate multilayer sheets did not swell in water to keep the original morphology. As a scaffold, the sheets having the calcium phosphate layer on the top supported the attachment and growth of L929 fibroblast cells. The enzymatic mineralization and the collagen/calcium phosphate composite sheets were discussed in conjunction with physicochemical and biological properties.