Oxalate Salts Research Articles

Stereoselective Lithiation and Carboxylation of Boc-Protected Bicyclopyrrolidine: Synthesis of a Key Building Block for HCV Protease Inhibitor Telaprevir

A stereoselective process for the manufacture of bicyclopyrrolidine 7 to 2 has been developed. The process utilizes a stereoselective lithiation/carboxylation sequence. The achiral diamine ligand DPBP induces excellent diastereocontrol, and resolution with (S)-THNA provides the corresponding salt of 8 in high er and dr. Subsequent processing of 8 gives 2 as the oxalate salt in an overall yield of 27% from 7 (based on total molar charge of 7). Compound 2 was obtained with high chemical and chiral purities. The process was successfully demonstrated on >100 kg scale.

Differential scanning calorimetry approach to investigate the transfer of the multitarget opioid analgesic LP1 to biomembrane model

An emerging approach in pain management is the use of multitarget opioid ligands, owing an improved analgesic effect coupled to a reduced incidence of side effects. With a mu opioid receptor agonist/delta opioid receptor antagonist profile, the benzomorphan-based compound LP1 belongs to multitarget ligands class. Previous in vivo investigations showed that LP1 – subcutaneously administered as oxalate salt – was an antinociceptive agent as potent as morphine with a low tolerance-inducing capability. Because the renal toxicity of oxalate is known, an alternative approach allowing the administration of LP1 freebase could be more biocompatible. In this study the interaction of LP1 freebase and LP1 oxalate salt with multilamellar vesicles, as membrane model, was evaluated using differential scanning calorimetry technique. Despite the good membrane interaction showed by LP1 freebase, it was not capable to diffuse in the aqueous medium and to be uptaken by multilamellar vesicles. On the other hand, LP1 freebase possessed a good transfer profile by a liposomal carrier to a biomembrane model. Considering our findings and the need of safe formulations, studies for the development of a suitable carrier for a systemic administration of LP1 freebase are in progress.

Gas‐phase fragmentation of metal adducts of alkali‐metal oxalate salts

Upon collisional activation, gaseous metal adducts of lithium, sodium and potassium oxalate salts undergo an expulsion of CO2, followed by an ejection of CO to generate a product ion that retains all three metals atoms of the precursor. Spectra recorded even at very low collision energies (2 eV) showed peaks for a 44-Da neutral fragment loss. Density functional theory calculations predicted that the ejection of CO2 requires less energy than an expulsion of a Na(+) and that the [Na3CO2](+) product ion formed in this way bears a planar geometry. Furthermore, spectra of [Na3C2O4](+) and [(39)K3C2O4](+) recorded at higher collision energies showed additional peaks at m/z 90 and m/z 122 for the radical cations [Na2CO2](+•) and [K2CO2](+•), respectively, which represented a loss of an M(•) from the precursor ions. Moreover, [Na3CO2](+), [(39)K3CO2](+) and [Li3CO2](+) ions also undergo a CO loss to form [M3O](+). Furthermore, product-ion spectra for [Na3C2O4](+) and [(39)K3C2O4](+) recorded at low collision energies showed an unexpected peak at m/z 63 for [Na2OH](+) and m/z 95 for [(39)K2OH](+), respectively. An additional peak observed at m/z 65 for [Na2(18)OH](+) in the spectrum recorded for [Na3C2O4](+), after the addition of some H2(18)O to the collision gas, confirmed that the [Na2OH](+) ion is formed by an ion-molecule reaction with residual water in the collision cell.

Tissue profiling by nanogold-mediated mass spectrometry and artificial neural networks in the mouse model of human primary hyperoxaluria 1

Correct assessment of tissue histopathology is a necessary prerequisite for any clinical diagnosis. Nowadays, classical methods of histochemistry and immunohistochemistry are complemented by various techniques adopted from molecular biology and bioanalytical chemistry. Mass spectrometry profiling or imaging offered a new level of tissue visualization in the last decade, revealing hidden patterns of tissue molecular organization. It can be adapted to diagnostic purposes to improve decisions on complex and morphologically not apparent diagnoses. In this work, we successfully combined tissue profiling by mass spectrometry with analysis by artificial neural networks to classify normal and diseased liver and kidney tissues in a mouse model of primary hyperoxaluria type 1. Lack of the liver l-alanine:glyoxylate aminotransferase catalyzing conversion of l-alanine and glyoxylate to pyruvate and glycine causes accumulation of oxalate salts in various tissues, especially urinary system, resulting in compromised renal function and finally end stage renal disease. As the accumulation of oxalate salts alters chemical composition of affected tissues, it makes it available for examination by bioanalytical methods. We demonstrated that the direct tissue MALDI-TOF MS combined with neural computing offers an efficient tool for diagnosis of primary hyperoxaluria type I and potentially for other metabolic disorders altering chemical composition of tissues.

Reactivity of nitrate and organic acids at the concrete–bitumen interface of a nuclear waste repository cell

This study investigates the fate of nitrate and organic acids at the bitumen–concrete interface within repository cell for long-lived, intermediate-level, radioactive wastes. The interface was simulated by a multiphase system in which cementitious matrices (CEM V cement paste specimens) were exposed to bitumen model leachates consisting of nitrates and acetic acid with and without oxalic acid, chemical compounds likely to be released by bitumen. Leaching experiments were conducted with daily renewal of the solutions in order to accelerate reactions. The concentrations of anions (acetate, oxalate, nitrate, and nitrite) and cations (calcium, potassium) and the pH were monitored over time. Mineralogical changes of the cementitious matrices were analysed by XRD. The results confirmed the stability of nitrates in the abiotic conditions of the experiments. The action of acetic acid on the cementitious matrix was similar to that of ordinary leaching in the absence of organic acids (i.e. carried out with water or strong acids); no specific interaction was detected between acetate and cementitious cations. The reaction of oxalic acid with the cementitious phases led to the precipitation of calcium oxalate salts in the outer layer of the matrix. The concentration of oxalate was reduced by 65% inside the leaching medium.

An Oxalate Method for Measuring the Surface Area of Nickel Electrodes

This work establishes a new method to measure the electrochemically active surface area (AECSA) of nickel electrodes, in situ. The addition of 0.08 mol L−1 of an oxalate salt to an alkaline electrolyte solution shifts the half-wave potential of the Ni(II)/Ni(III) redox pair by about −80 mV. Further, these peaks are very narrow. The sharpest peak in this work has a full width at half maximum (FWHM) of just 11 mV. This unusual sharpness is attributed to the layered structure of nickel hydroxides and the adsorption of oxalate from the solution on the (001) surface. This is supported by attenuated total reflectance infrared (ATR-IR) peaks measured at 1265 cm−1, 1655 cm−1, and 1713 cm−1, which correspond to mononuclear bidentate oxalate bonded to nickel. At sufficiently fast potential scan rates (≥150 mV s−1), the adsorbed oxalate limits growth of the surface hydroxide to a single layer. During the reverse scan, the surface NiOOH/Ni(OH)2 reduction peak is well-separated from other electrochemical processes and may be used to accurately and precisely measure the AECSA. The error of this method is estimated at < 10%.

Synthesis and Antiproliferative Activity of Some Androstene Oximes and Their O‐Alkylated Derivatives

In order to study the structure-activity relationship with respect to the cytotoxicity of steroidal oximes, several 6E-hydroximino-4-ene steroids and their O-alkylated derivatives were synthesized. The oxime ethers were solidified and purified by preparing their corresponding oxalate salts. The new derivatives as well as some previously synthesized ones were evaluated for in vitro antineoplastic activity against a panel of 60 cancer cell lines at 10 µM. The oximes and oxime ethers were found to have moderate to good antiproliferative activity against various leukemia, colon, melanoma, and renal cancer cell lines.

From ascorbic acid to oxalate: Hydrothermal synthesis of copper oxalate microspheres and conversion to oxide

Copper oxalate microspheres of about 10μm in size are obtained via a hydrothermal route. Instead of oxalic acid or soluble oxalate salts, ascorbic acid is used with copper nitrate in the reaction. Obtained copper oxalate microspheres are characterized by several techniques. Further heating copper oxalate microspheres yields porous copper oxide microspheres of similar size.

Synthesis, structural characterization, and magnetic property of nanostructured ferrite spinel oxides (AFe2O4, A = Co, Ni and Zn)

Nanostructured ferrite spinels AFe2O4 (A = Co, Ni, Zn) were successfully synthesized via a co-precipitation method using oxalate salt as a precursor in an anionic surfactant system in combination with a simple calcination process. High crystallinity samples of nanoparticle spinels in a grain size range of 15–100 nm were obtained by varying the calcination temperature (300–700 °C) and time (1–5 h). Their pore sizes were controlled in a range of 3 nm up to a hundred nm by tailoring the calcination conditions. Raising the calcination temperature was found to decrease the Brunauer–Emmett–Teller (BET) surface area, and broaden the pore structure due to enhanced crystal growth and agglomeration of interparticles of spinels. Transmission electron microscopy (TEM) images of ferrite spinels calcined at 300 °C showed mesoporous structures with narrow pore size distribution, and the maximum BET surface area of CoFe2O4, NiFe2O4 and ZnFe2O4 were found at 201 (Co), 315 (Ni), and 273 (Zn) m2 g−1, respectively. The magnetic hysteresis loops of the ferrite spinels at room temperature demonstrated ferromagnetism in CoFe2O4, superparamagnetism–ferromagnetism in NiFe2O4, and paramagnetism in ZnFe2O4. The highest saturation magnetization (Ms), remanent magnetization (Mr), and coercivity (Hc) were obtained from high crystallinity spinels calcined at 700 °C. Nanostructured AFe2O4 with high surface area and mesoporosity promises potentials as novel magnetic catalysts.

Ketoconazole Salt and Co-crystals with Enhanced Aqueous Solubility

Crystal structures of ketoconazole oxalate salt (1) and three co-crystals with fumaric (2), succinic (3), and adipic (4) acids in 1:1 stoichiometry were determined by single-crystal X-ray diffraction in which 1 forms oxalate dimers involved in ionic interaction with the imidazole ring of ketoconazole molecules, while 2–4 display 4-member circuit networks between hydrogen-bonded ketoconazole and coformer molecules. The salt and co-crystal nature of 1–4 was confirmed by combining single-crystal X-ray diffraction, ss-NMR, and lattice energy calculations. Ketoconazole molecules show highly similar conformations and crystal packing in co-crystals 2 and 3, while different conformers are present in the 1, 2, and 4 structures. For all salt and co-crystals, powder dissolution measurements revealed a significant solubility improvement compared to ketoconazole, and the solubility of 1–4 is contrary to the solubility values of the corresponding acids. A 100-fold solubility increase in water was obtained by ketoconazo...

Theoretical modeling of the urinary supersaturation of calcium salts in healthy individuals and kidney stone patients: Precursors, speciation and therapeutic protocols for decreasing its value

BackgroundSupersaturation (SS) of urinary salts has been extensively invoked for assessing the risk of renal stone formation, but precursors have often been ignored. Our objectives were to establish by computer modeling, which urinary components are essential for calculating reliable SS values, to investigate whether unique equilibrium processes occur in the urine of stone formers (SF) which might account for their higher SS levels relative to healthy controls (N), to determine the relative efficacies of three different, widely-used protocols for lowering urinary SS of calcium salts and to examine the influence of precursors. MethodsUrinary data from published studies were consolidated into three N–SF cohort pairs and were selected for modeling using the speciation program JESS. SS values of calcium oxalate monohydrate (COM) and its precursors calcium oxalate di- and tri-hydrate (COD, COT), as well as those of hydroxyapatite (HAP) and its precursors octacalcium phosphate (OCP) and brushite (Bru) were calculated. A pragmatic approach for the statistical analysis of the modeling outputs was developed and applied. ResultsThirteen urinary parameters were identified as being crucial for the accurate calculation of SS of calcium oxalate (CaOx) and calcium phosphate (CaP) salts. Chloride, sulfate and ammonium, or combinations thereof, have frequently been omitted from SS calculations, thereby giving erroneously high values for these parameters. Subtle differences occur in the urinary equilibrium processes of SF and N. SS (OCP) and SS (HAP) are more sensitive to dilution effects than the other urinary salts. Decreasing urinary Ca and decreasing Ox are equally efficacious in reducing SS of CaOx salts, and are marginally superior to increasing urinary volume. Decreasing urinary calcium and increasing urinary volume are equally efficacious in reducing SS of CaP salts. SS of precursors follow the Ostwald Lussac empirical rule and undergo the same changing trends in different urinary scenarios. ConclusionsResearchers are advised to include all of the 13 identified urinary parameters in their calculations of SS of Ca salts, in order to attain better accuracy. Differences in achieving speciation equilibria in N and SF contribute towards higher values of SS in SF, but in a minor way only. Increasing urinary volume is confirmed as the most realistically efficacious strategy for decreasing SS of urinary calcium salts. SS of HAP should be assigned equal importance to that of Bru in considering the stone-forming potential of urine. Precursors of CaOx and CaP salts should be taken into account when investigating stone forming mechanisms.

Nocturnal Home Hemodialysis for a Patient With Type 1 Hyperoxaluria

Type 1 primary hyperoxaluria is a genetic disorder caused by deficiency of the liver-specific peroxisomal enzyme alanine-glyoxylate aminotransferase. This enzyme deficiency leads to excess oxalate production and deposition of calcium oxalate salts, resulting in kidney failure and systemic oxalosis. Aside from combined liver/kidney transplantation, no curative treatment exists. Various strategies for optimizing dialysis treatment have been evaluated, but neither conventional hemodialysis nor peritoneal dialysis can keep pace with oxalate production in this patient population. In this report, we describe a patient with end-stage renal disease from type 1 primary hyperoxaluria managed with nocturnal home hemodialysis. Performing hemodialysis 8-10 hours each night with blood flow of 350 mL/min and total dialysate volume of 60 L, she has maintained pre- and postdialysis serum oxalate levels at or below the level of supersaturation. We also review published literature regarding oxalate removal in various modalities of dialysis in patients with type 1 primary hyperoxaluria. In our patient, nocturnal hemodialysis has controlled serum oxalate levels better than conventional hemodialysis therapies. Home nocturnal hemodialysis should be considered an option for management of patients with end-stage renal disease from type 1 hyperoxaluria who are awaiting transplantation.

Acetate Induced Enhancement of Photocatalytic Hydrogen Peroxide Production from Oxalic Acid and Dioxygen

The addition of acetate ion to an O2-saturated mixed solution of acetonitrile and water containing oxalic acid as a reductant and 2-phenyl-4-(1-naphthyl)quinolinium ion (QuPh(+)-NA) as a photocatalyst dramatically enhanced the turnover number of hydrogen peroxide (H2O2) production. In this photocatalytic H2O2 production, a base is required to facilitate deprotonation of oxalic acid forming oxalate dianion, which acts as an actual electron donor, whereas a Brønsted acid is also necessary to protonate O2(•-) for production of H2O2 by disproportionation. The addition of acetate ion to a reaction solution facilitates both the deprotonation of oxalic acid and the protonation of O2(•-) owing to a pH buffer effect. The quantum yield of the photocatalytic H2O2 production under photoirradiation (λ = 334 nm) of an O2-saturated acetonitrile-water mixed solution containing acetate ion, oxalic acid and QuPh(+)-NA was determined to be as high as 0.34, which is more than double the quantum yield obtained by using oxalate salt as an electron donor without acetate ion (0.14). In addition, the turnover number of QuPh(+)-NA reached more than 340. The reaction mechanism and the effect of solvent composition on the photocatalytic H2O2 production were scrutinized by using nanosecond laser flash photolysis.

Investigating the Stability of Double Head to Tail Dimers and Ribbons in Multicomponent Crystals of cis-4-Aminocyclohexanecarboxilic Acid with Water and Oxalic Acid

The current contribution aims to investigate the stability of commonly occurring motifs present in certain amino acid structures after introducing additional molecules to form multicomponent crystals. The crystal structures of the amino acid cis-4-aminocyclohexanecarboxylic acid hemihydrate I and dehydrate II forms and that of its oxalate salt cocrystallized with oxalic acid III, were investigated employing a combination of techniques. Both single-crystal and powder X-ray diffraction were used to solve the structures, while temperature-control powder X-ray diffraction was used to follow the dehydration of I. Regardless of the added molecules that induce modifications of the intermolecular interactions within the crystals, some recurring supramolecular structures were identified: double head to tail dimers, graph symbol R22(16), and ribbons, graph symbol R22(16)R34(10). Stabilities of these supramolecular motifs were investigated using theoretical modeling with DFT/B3LYP/6-31++G (d,p) and PM6-D2H calculations. The theoretical calculations reproduced the experimental findings, confirming the extraordinary stability of these motifs. The molecular recognition of amino acid pairs to form double head to tail-dimers is undoubtedly the initial driving force for the crystal formation in all the three crystals investigated.

Physico-chemical interactions at the concrete-bitumen interface of nuclear waste repositories

This study investigates the fate of nitrate and organic acids at the bitumenconcrete-steel interface within a repository storage cell for long-lived, intermediatelevel, radioactive wastes. The interface was simulated by a multiphase system in which cementitious matrices (CEM V paste specimens) were exposed to bitumen model leachates consisting of nitrates and acetic acid with and without oxalic acid, chemical compounds likely to be released by bitumen. Leaching experiments were conducted with daily renewal of the solutions in order to accelerate reactions. C-steel chips, simulating the presence of steel in the repository, were added in the systems for some experiments. The concentrations of anions (acetate, oxalate, nitrate, and nitrite) and cations (calcium, potassium, ammonium) and the pH were monitored over time. Mineralogical changes of the cementitious matrices were analysed by XRD. The results confirmed the stability of nitrates in the absence of steel, whereas, reduction of nitrates was observed in the presence of steel (production of NH4+). The action of acetic acid on the cementitious matrix was similar to that of ordinary leaching; no specific interaction was detected between acetate and cementitious cations. The reaction of oxalic acid with the cementitious phases led to the precipitation of calcium oxalate salts in the outer layer of the matrix. The concentration of oxalate was reduced by 65% inside the leaching medium.

Malachite Green Toxicity and Effects on Reproductive Success in Zebrafish Danio rerio

Malachite green (MG) is frequently used to treat fish pathogens in zebrafish, but little is known about how MG may affect the physiological processes that are targets of research investigations. This study evaluated the effects of MG on reproductive success in zebrafish, Danio rerio, and the relative toxicity of MG oxalate and MG chloride salts. After 5-day exposure to a prophylactic concentration (0.065 mg/L) of MG oxalate, the percentage of spawning pairs significantly declined (57.5%±8.5 SE) and then returned to pre-exposure levels (89%±6.6 SE) within one week. Embryo and larval survival were not affected by exposure of parents to MG; however, when exposed directly, MG oxalate was more toxic than MG chloride in both life stages. The LC(50) for embryos was 0.067 μM and 0.116 μM for MG oxalate and MG chloride, respectively, and the LC(50) for larvae, 0.057 μM and 0.103 μM, respectively. Other than a transient reduction in the number of fish that spawned, MG treatment of broodstock did not impact reproductive success, which indicates that MG can be used prophylactically with minimal effects on reproduction. Based on acute toxicity, MG chloride should be preferred over MG oxalate.

Impacts of biomass burning smoke on the distributions and concentrations of C2–C5 dicarboxylic acids and dicarboxylates in a tropical urban environment

Daily ambient PM2.5 was collected during 8 September to 5 October (Julian Days, JDs 252–279), 2008 in Singapore to investigate impacts of transboundary biomass burning smoke on distribution among C2–C5 dicarboxylic acids (DCAs) and corresponding dicarboxylate salts (DCS) in the tropical urban atmosphere. Quantification of DCAs and DCS were performed using solvent and water extraction followed by chromatography analyses via GC–MS and ion chromatography. The averaged PM2.5 and PM10 concentrations from September 19–30 (JDs 263–274) were concurrently elevated by ∼40% due to the transboundary smoke. During this same period, C2–C5 total dicarboxylates (TDCAS, summation of DCAs and DCS), on average, increased more than two times, with C2-TDCAS accounted for in average 80% of the C2–C5 TDCAS. This demonstrates that the transboundary smoke enriched C2–C5 TDCAS more than PM2.5 in the urban environment. In the presence of the transboundary smoke, the averaged concentration ratios of C2–C5 DCS to corresponding DCA were 13.4, 2.9, 1.0, and 1.4 with oxalate salts exhibiting the highest concentration (355.0 ng m−3). The transboundary smoke increased malic acid concentration more than 3.5 times, which is the largest relative increase among the quantified TDCAS. Considering that malic acid is mainly generated through ambient photooxidation, such significant increase in malic acid demonstrates more prominent photooxidation incurred by the smoke.

Analysis of the Leaching Efficiency of Inhibited Water and Tank Simulant in Removing Residues on Thermowell Pipes

A cleaning protocol was determined and modeled, using the shrinking core model, for the removal of a solid residue coating thermo well pipes contained in the riser of a Savannah River Site (SRS) waste tank (Tank 48H). The solid residues on two sets of thermo well pipe samples removed from the D2 riser in SRS Tank 48H were characterized by high performance liquid chromatography (HPLC), ion chromatography (IC) and gamma spectroscopy. The residue thickness was determined using the ASTM standard D 3483-05 and was found to be three orders of magnitudes below the 1 mm thickness estimated from an earlier video of the tank cooling coil inspection. The actual estimated thickness ranged from 4 to 20.4 microns. The mass per unit area ranged from 0.15 to 0.82 milligrams per square centimeter. The residues appear to consist primarily of potassium tetraphenylborate (39.8 wt% KTPB) and dried salt solution (33.5 wt% total of nitrates, nitrites, and oxalate salts), although ∼30% of the solid mass was not accounted for in the mass balance. No evidence of residue buildup was found inside the pipe, as expected. Two aqueous solutions representing waste processing streams were chosen for the cleaning trials. The residue leaching characteristics were measured by placing one pipe in inhibited water (0.01 M NaNO2 and 0.01 M NaOH) and one pipe in Defense Waste Processing Facility (DWPF) Recycle simulant (primarily 0.20 M NaNO2 and 0.18 M NaOH). After soaking for less than 4 weeks, the inhibited water was 95.4% effective at removing the residue and the DWPF Recycle simulant was 93.5% effective. The surface appearance of the pipes after leaching tests appeared close to the clean shiny appearance of a new pipe. Total gamma counts of leachates averaged 48.1 dpm/mL, or an equivalent of 2.35E-11 Ci/gm Cs-137 (dry solids basis), which is much lower than the 1.4 E-03 Ci/gm expected for Tank 48H dry slurry solids.

Crystal engineering approach to improve the solubility of mebendazole

An anthelmintic drug, mebendazole, shows a very low bioavailability (less than 10%) due to its poor aqueous solubility (0.035 mg/mL at 25 °C for form C). To improve its solubility, we combined a group of dicarboxylic acids with mebendazole via liquid-assisted grinding and reaction crystallization methods, and two salts with oxalic and maleic acids, as well as two co-crystals with malonic and glutaric acids, were obtained. These novel multi-component complexes were characterized by powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analyses and infrared spectra. The single-crystal structures of mebendazole-maleate salt, mebendazole-glutaric acid co-crystal, and mebendazole-monomethyl oxalate salt, in which one of the carboxyl groups of oxalic acid was esterified during the single-crystal growth in methanol, were determined. It was observed that mebendazole combines dicarboxylic acid/ester via a R22(8) hydrogen-bonding motif that involves a carbamyl benzimidazole and a carboxyl group, resulting in the 1:1 stoichiometry. The powder dissolution studies revealed that the apparent solubility of the complexes was significantly increased after the formation of co-crystals and salts.

Self-assembly of colloidal sulfur particles influenced by sodium oxalate salt on glass surface from evaporating drops

Evaporation of sessile droplets containing colloidal particles induces outward flow within the drop, which produces the well-known “coffee-ring” effect or a dense ring-like deposition along the perimeter. In this work, the formation of a self-assembled structure during drying of microlitre drops on the glass surface, containing colloidal sulfur particles (synthesized in situ by the reaction of oxalic acid and sodium thiosulphate), is investigated experimentally with help of optical microscopy. Our results show that the particles are self-assembled into a tree-like structure after the evaporation of liquid drops taken from the reaction mixture. The sulfur particles alone cannot form similar self-assembly structures in pure water, but the sodium oxalate salt present in the reaction mixture helps to form the tree-like structure. The structure formation is also influenced by evaporative flux inside the liquid drop, and capillary and van der Waals attractive forces between the particles. The different parameters such as particle size, particle and salt concentration, acid to thiosulphate ratio, drop volume and addition of surfactants strongly influences the structure formation.