Hydroxymethylphosphonic Acid Research Articles

Cationic polymerization of cyclic trimethylene carbonate induced with initiator and catalyst in one molecule: Polymer structure, kinetics and DFT

Trimethylene carbonate, the monomer that can be prepared from CO2 and 1,3-propanediol, was polymerized cationically, according to the activated monomer mechanism, as it follows from the polymerization kinetics and the DFT studies. Polymerization provides the biocompatible, degradable polymer and was conducted with initiator and catalyst in one molecule (CINICAT). This is in contrast to the known processes when protonic acids (organocatalysts) require addition of an independent initiator and then the low molar mass catalyst, left free in the polymer, may diffuse to its surface, changing the properties. The used CINICAT: hydroxymethylphosphonic acid {HOCH2P(=O)(OH)2} is quantitatively embedded in the polymer molecules. Polymerization is living/controlled and provides at 100 °C, in bulk, polymers with molar masses ∼104 g/mol. The acidic end groups were further used for polymer functionalization and in reaction with diepoxybutane were quantitatively converted into reactive epoxy groups.

Synthesis and Properties of Functionalized Poly(ε-caprolactone); Chain Polymerization Followed by Polycondensation in One Pot with Initiator and Catalyst in One Molecule. Synthesis and Molecular Structures

Poly(ε-caprolactone) and polylactide are biocompatible and biodegradable polymers. Both are hydrophobic, and their backbones do not contain reactive groups. The existing methods of functionalization are mostly based on copolymerization with functional comonomers that require additional syntheses. In the method of functionalization described in this work, special end groups are introduced that allow, after chain polymerization of ε-caprolactone (CL), the following step, in one pot, namely polycondensation. Chain polymerization was initiated/catalyzed by hydroxymethylphosphonic acid. Since one of the end groups contains two acidic groups, one is used in polycondensation with the hydroxyl group from the other end group and the other one, becoming less reactive, is introduced to the polymer chains. Thus, polymer chains contain phosphoacidic groups along the chain. When, for example, CL was the first chain polymerized to an oligomer of the molar mass ∼3 × 103 g·mol–1, its further polycondensation resulted in polymers with a molar mass approaching ∼105 g·mol–1, with ∼30 acidic groups along the statistical chain.

Capillary electrophoresis applied for the determination of acidity constants and limiting electrophoretic mobilities of ionizable herbicides including glyphosate and its metabolites and for their simultaneous separation.

Thermodynamic acidity constants and limiting ionic mobilities were determined for polyprotic non-chromophore analytes using capillary electrophoresis with capacitively coupled contactless conductivity detection. It was not necessary to work with buffers of identical ionic strength as ionic strength effects on effective electrophoretic mobilities were corrected by modeling during data evaluation (software AnglerFish). The mobility data from capillary electrophoresis coupled to conductivity detection were determined in the pH range from 1.25 to 12.02 with a high resolution (36pH steps). With this strategy, thermodynamic acidity constants and limiting ionic mobilities for various acidic herbicides were determined, sometimes for the first time. The model analytes included glyphosate, its metabolites, and its acetylated derivates (aminomethyl phosphonic acid, glyoxylic acid, sarcosine, glycine, N-acetyl glyphosate, N-acetyl aminomethyl phosphonic acid, hydroxymethyl phosphonic acid). The obtained data were used in simulations to optimize separations by capillary electrophoresis. Simulations correlated very well to experimental results. With the new method, the separation of glyphosate from interfering components like phosphate in beer samples was possible.

Catalysis in polymerization of cyclic esters. Catalyst and initiator in one molecule. Polymerization of ε-caprolactone

This study demonstrates that in the cationic ring-opening polymerization of cyclic esters, leading to biocompatible and biodegradable polymers, catalyst and initiator could be efficient when are in the same molecule (CINICAT). This is in contrast to the known processes when organocatalysts (e.g., protonic acids) require addition of an independent initiator and then low molar mass catalyst is left free in polymer. We have shown that hydroxymethyl phosphonic acid and 11-hydroxyundecaphosphonic acid act simultaneously as catalysts and initiators, becoming stable end-groups of the macromolecules (MALDI and DOSY). It follows from kinetic analysis that polymerization with these CINICATs is living/controlled.

Evaluation of apoptotic potential of glyphosate metabolites and impurities in human peripheral blood mononuclear cells (in vitro study)

Glyphosate is used for cereal, vegetable and fruit crops for reducing or inhibiting the growth of weeds as well as a desiccant for various grain crops. That is why, glyphosate has been shown to be accumulated in humans and animals through ingestion of food of both plant and animal origin.The study aimed to assessed the effect of glyphosate, its metabolites: aminomethylphosphonic acid (AMPA), methylphosphonic acid and its impurities: PMIDA, N-methylglyphosate, hydroxymethylphosphonic acid and bis(phosphonomethyl)amine on apoptosis induction in human peripheral blood mononuclear cells (PBMCs). PBMCs were exposed to the compounds studied at the concentrations ranging from 0.01 to 5 mM for 4 h.We have observed an increase in reactive oxygen species (including hydroxyl radical) and cytosolic calcium ions levels as well as reduction of transmembrane mitochondrial potential (ΔΨm) in PBMCs exposed to the compounds examined. All substances studied changed PBMCs membrane permeability, activated caspase-8, -9, -3 and caused chromatin condensation, which showed that they were capable of inducing apoptosis both via extrinsic and particularly intrinsic pathway.Generally the study demonstrated that there were no differences between apoptotic changes induced by glyphosate, its metabolites or impurities, and observed changes were provoked by high concentrations of investigated compounds.

Degradation of nitrilotris-methylenephosphonic acid (NTMP) antiscalant via persulfate photolysis: Implications on desalination concentrate treatment

Nitrilotris-methylenephosphonic acid (NTMP) has been widely used as an antiscalant in reverse osmosis (RO) desalination and other industrial processes to inhibit scaling from calcium and other hardness ions. Removal of NTMP from RO concentrate can induce the precipitation of oversaturated scale-forming substances, enable additional water recovery from RO concentrate, and reduce the risk of eutrophication after brine disposal. This study investigated the kinetics and mechanisms of oxidative degradation of NTMP by UV photolysis of persulfate at 254 nm. Results showed that NTMP was effectively degraded by persulfate photolysis and the reaction followed pseudo first-order kinetics. The degradation of NTMP was favorable at circumneutral pHs but significantly inhibited in highly alkaline conditions (e.g., pH of 11.5), mainly due to the reduced concentration of SO4•−. Using a competition reaction kinetics approach, the second-order rate constants of NTMP with SO4•− and HO• were determined to be (2.9 ± 0.6) × 107 M−1s−1 and (1.1 ± 0.1) × 108 M−1s−1, respectively. SO4•− had a predominant contribution to NTMP degradation (62%–95%), because the steady-state concentration of SO4•− was 11–54 times higher than that of HO• at pHs between 4 and 11.5. NTMP degradation rate increased with an increase in persulfate dosage and a decrease in NTMP concentration. In the real RO concentrate, NTMP degradation rate was impacted by the presence of chloride and bicarbonate. The degradation of NTMP started with the cleavage of C–N bonds, and then generated intermediates including iminodi(methylene)phosphonate, hydroxymethylphosphonic acid and aminotris(methylenephosphonic acid), which were eventually mineralized into ammonia, phosphate and carbon dioxide. This study demonstrated that UV/persulfate is a promising technology to remove phosphonate antiscalants from RO concentrate.

An Oxidative Pathway for Microbial Utilization of Methylphosphonic Acid as a Phosphate Source.

Methylphosphonic acid is synthesized by marine bacteria and is a prominent component of dissolved organic phosphorus. Consequently, methylphosphonic acid also serves as a source of inorganic phosphate (Pi) for marine bacteria that are starved of this nutrient. Conversion of methylphosphonic acid into Pi is currently only known to occur through the carbon-phosphorus lyase pathway, yielding methane as a byproduct. In this work, we describe an oxidative pathway for the catabolism of methylphosphonic acid in Gimesia maris DSM8797. G. maris can use methylphosphonic acid as Pi sources despite lacking a phn operon encoding a carbon-phosphorus lyase pathway. Instead, the genome contains a locus encoding homologues of the non-heme Fe(II) dependent oxygenases HF130PhnY* and HF130PhnZ, which were previously shown to convert 2-aminoethylphosphonic acid into glycine and Pi. GmPhnY* and GmPhnZ1 were produced in E. coli and purified for characterization in vitro. The substrate specificities of the enzymes were evaluated with a panel of synthetic phosphonates. Via 31P NMR spectroscopy, it is demonstrated that the GmPhnY* converts methylphosphonic acid to hydroxymethylphosphonic acid, which in turn is oxidized by GmPhnZ1 to produce formic acid and Pi. In contrast, 2-aminoethylphosphonic acid is not a substrate for GmPhnY* and is therefore not a substrate for this pathway. These results thus reveal a new metabolic fate for methylphosphonic acid.

The Impact of Glyphosate, Its Metabolites and Impurities on Viability, ATP Level and Morphological changes in Human Peripheral Blood Mononuclear Cells.

The toxicity of herbicides to animals and human is an issue of worldwide concern. The present study has been undertaken to assess toxic effect of widely used pesticide—glyphosate, its metabolites: aminomethylphosphonic acid (AMPA) and methylphosphonic acid and its impurities: N-(phosphonomethyl)iminodiacetic acid (PMIDA), N-methylglyphosate, hydroxymethylphosphonic acid and bis-(phosphonomethyl)amine on human peripheral blood mononuclear cells (PBMCs). We have evaluated the effect of those compounds on viability, ATP level, size (FSC-A parameter) and granulation (SSC-A parameter) of the cells studied. Human peripheral blood mononuclear cells were exposed to different concentrations of glyphosate, its metabolites and impurities (0.01–10 mM) for 4 and 24 h. It was found that investigated compounds caused statistically significant decrease in viability and ATP level of PBMCs. The strongest changes in cell viability and ATP level were observed after 24 h incubation of PBMCs with bis-(phosphonomethyl)amine, and particularly PMIDA. Moreover, all studied compounds changed cell granularity, while PMIDA and bis-(phosphonomethyl)amine altered PBMCs size. It may be concluded that bis-(phosphonomethyl)amine, and PMIDA caused a slightly stronger damage to PBMCs than did glyphosate. Changes in the parameters studied in PBMCs were observed only at high concentrations of the compounds examined, which clearly shows that they may occur in this cell type only as a result of acute poisoning of human organism with these substances.

Complexation of calix[4]arene hydroxymethyl-phosphonic acid with tryptophan and N-acetyl-tryptophan amide

The Host-Guest complexation of calixarene hydroxymethylphosphonic acid with tryptophan and N-acetyltryptophan amide has been investigated by the RP HPLC method in H2O/MeCN (99/1) solution (column support Hypersil CN, UV-detector, λ = 254 nm). Adsorption of calixarene hydroxymethylphosphonic acid on the Hypersil CN surface has been studied. It has been found that hydroxymethylphosphonic acid is characterized by reversible sorption on the Hypersil CN surface. The binding constants (KA = 23000 M-1 and 39000 M-1 for tryptophan and N-acetyltryptophan amide, respectively) of the supramolecular complexes have been calculated from the ratio between the capacity factors k’ of the Guest and the calixarene hydroxymethylphosphonic acid Host concentration in the mobile phase. The Gibbs free energies of the tryptophan and N-acetyltryptophan amide complexes are -24.84 and -26.15 kJ/mol, respectively. The molecular modelling of calixarene hydroxymethylphosphonic acid and its complexes with tryptophan and N-acetyltryptophan amide (Hyper Chem, version 8, force field PM3) has indicated that the complexes are stabilized by hydrogen bonds, electrostatic, π-π, and solvatophobic interactions. The geometric parameters of the energy minimized calixarene macrocycle and its complexes with tryptophan and N-acetyltryptophan amide have been calculated. According to the calculations it has been shown that the Host-Guest complexation does not change the flattened-cone conformation of calixarene. Finally, the inverse correlation has been found between the KA values of the complexes and the Log P values of the guest molecules.

The effect of metabolites and impurities of glyphosate on human erythrocytes (in vitro)

The toxicity of herbicides to animals and human is an issue of worldwide concern. The present study was undertaken to evaluate toxic potential of widely used pesticide – glyphosate, its metabolites: aminomethylphosphonic acid (AMPA); methylphosphonic acid and its impurities: N-(phosphonomethyl)iminodiacetic acid (PMIDA), N-methylglyphosate, hydroxymethylphosphonic acid and bis-(phosphonomethyl)amine.We evaluated the effect of those compounds on hemolysis, hemoglobin oxidation, reactive oxygen species (ROS) formation and changes in morphology of human erythrocytes. The erythrocytes were exposed to different concentrations of glyphosate and its metabolites and impurities (0.01–5mM) for 1, 4 and 24h.Glyphosate, its metabolites and impurities induced a little hemolysis and hemoglobin oxidation. All changes were very low, even after 24h incubation. Most of the investigated compounds induced reactive oxygen species formation from 0.25mM, except the N-methylglyphosate which caused an increase in ROS formation from 0.5mM. Moreover, the investigated xenobiotics did not change the size and shape (except bis-(phosphonomethyl)amine) of the human erythrocytes.Changes in human erythrocytes were observed only when high concentrations of the compounds were applied. Some investigated metabolites and impurities caused a slight stronger damage to human erythrocytes than a glyphosate.The results clearly show that the changes induced in the erythrocytes can occur only as a result of poisoning with these compounds.

Calix[4]arene-α-hydroxyphosphonic acids. Synthesis, stereochemistry, and inhibition of glutathione S-transferase

A series of dipropoxy-, tripropoxy- and tetrapropoxycalix(4)arenes bearing one or two fragments of α-hydroxymethylphosphonic acid at the upper rim of the macrocycle was prepared by the reaction of the corresponding mono- and di-formylcalixarenes with sodium salts of dialkyl phosphites or with trialkyl (tristrimethylsilyl)phosphites followed by dealkylation (desilylation) of the ester derivatives. The conformations of the macrocyclic skeleton and the stereoisomeric forms of the compounds obtained were investigated by 1 H NMR. The resulting α- hydroxymethylphosphonic acids were found to be able to inhibit the activity of glutathione S- transferase in vitro.

Hydrogen bonded framework structures constructed from 2-(pyridyl N-oxide) methylphosphonic acid ligands and erbium(III).

Syntheses for 2-(pyridyl N-oxide) methylphosphonic acid, 1-H, and 2-(pyridyl N-oxide) hydroxymethylphosphonic acid, 4-H, are described, and the crystal structures of both ligands are presented. Combination of these ligands with freshly prepared erbium hydroxide results in the formation of the isostructural complexes Er(L(-))(3)(LH).8H(2)O. The crystal structure determinations of the complexes show that extensive hydrogen bonding links the individual eight coordinate Er(L(-))(3)(LH) molecular units into a 3-D structure.

The Purification and Characterization of Phosphonopyruvate Hydrolase, a Novel Carbon-Phosphorus Bond Cleavage Enzyme from Variovorax sp. Pal2

Phosphonopyruvate hydrolase, a novel bacterial carbon-phosphorus bond cleavage enzyme, was purified to homogeneity by a series of chromatographic steps from cell extracts of a newly isolated environmental strain of Variovorax sp. Pal2. The enzyme was inducible in the presence of phosphonoalanine or phosphonopyruvate; unusually, its expression was independent of the phosphate status of the cell. The native enzyme had a molecular mass of 63 kDa with a subunit mass of 31.2 kDa. Activity of purified phosphonopyruvate hydrolase was Co2+-dependent and showed a pH optimum of 6.7-7.0. The enzyme had a Km of 0.53 mm for its sole substrate, phosphonopyruvate, and was inhibited by the analogues phosphonoformic acid, 3-phosphonopropionic acid, and hydroxymethylphosphonic acid. The nucleotide sequence of the phosphonopyruvate hydrolase structural gene indicated that it is a member of the phosphoenolpyruvate phosphomutase/isocitrate lyase superfamily with 41% identity at the amino acid level to the carbon-to-phosphorus bond-forming enzyme phosphoenolpyruvate phosphomutase from Tetrahymena pyriformis. Thus its apparently ancient evolutionary origins differ from those of each of the two carbon-phosphorus hydrolases that have been reported previously; phosphonoacetaldehyde hydrolase is a member of the haloacetate dehalogenase family, whereas phosphonoacetate hydrolase belongs to the alkaline phosphatase superfamily of zinc-dependent hydrolases. Phosphonopyruvate hydrolase is likely to be of considerable significance in global phosphorus cycling, because phosphonopyruvate is known to be a key intermediate in the formation of all naturally occurring compounds that contain the carbon-phosphorus bond.

SYNTHESIS OF PHOSPHONIC ANALOGUES OF γ-GLUTAMYL TRIPEPTIDES AND DEPSIPEPTIDES

Abstract The analogues of biologically active ophthalmic (γ-L-glutamyl-α-L-aminobutyrylglycine) and norophthalmic (γ-L-glutamyl-L-alanylglycine) acids containing the phosphonic analogue of glycine or glycolic acid have been synthesized by standard procedure. The key intermediates were P-terminal di-p-nitrobenzyl phosphonodipeptides and phosphonodidepsipeptides derivatives of amino and hydroxymethyl-phosphonic acids.

Phosphonocarboxylic acids as specific inhibitors of Na+-dependent transport of phosphate across renal brush border membrane.

We investigated interactions of phosphonoformic acid (PFA), phosphonoacetic acid (PAA), and other phosphonyl derivatives with the Na+ gradient [Na+ extravesicular greater than Na+ intravesicular; Nao+ greater than Na+i]-dependent transport system for phosphate (Pi) in renal cortical brush border membrane vesicles (BBMV). PFA and PAA inhibited in a dose-dependent manner the Na+ gradient [Na+o greater than Na+i]-dependent uptake of Pi by rat kidney BBMV. PFA was a more potent inhibitor than PAA while phosphonopropionic acid, hydroxymethylphosphonic acid, and phenylphosphonic acid had no effect on Pi transport. The inhibitory effect of PFA was competitive (Ki approximately equal to 4.6 X 10(-4) M) and reversible upon dilution. The uptake of Pi by BBMV in the absence of Na+ gradient [Nao+ = Na+i] was also inhibited by PFA. The PFA had no effect on uptake of L-[3H]proline, D-[3H]glucose, or 22Na+ by BBMV nor did it alter intravesicular volume of BBMV. The relative (%) extent of inhibition by PFA was not altered by changes in the extravesicular pH or changes in the steepness of the Na+ gradient [Nao+ greater than Na+i]. The inhibition of PFA was analogous in renal BBMV from rats, mice, rabbits, or dogs. Unlike other known inhibitors of brush border membrane (BBM) transport of Pi, e.g. arsenate, NAD, and ethane-1-hydroxy-1,1-diphosphonate, PFA and PAA had no inhibitory effect on BBM-bound or solubilized alkaline phosphatase. Also, PFA did not interfere with the activity of renal cortical (Na-K)ATPase. Administration of PFA (0.5 g/kg/day, intraperitoneally) to thyroparathyroidectomized rats fed a low Pi diet elicited an increase in urinary excretion of Pi, but did not change the excretion of Na+, K, and Ca2+. The results show that the PFA, and to a lesser degree PAA, are specific competitive inhibitors of the Na+-Pi cotransport in renal cortical BBM and are suitable probes for studies of this transport system.

Studies on the biosynthesis of bialaphos (SF-1293). 4. Production of phosphonic acid derivatives, 2-hydroxyethylphosphonic acid, hydroxymethylphosphonic acid and phosphonoformic acid by blocked mutants of Streptomyces hygroscopicus SF-1293 and their roles in the biosynthesis of bialaphos.

Studies on the biosynthesis of bialaphos (SF-1293). 4. Production of phosphonic acid derivatives, 2-hydroxyethylphosphonic acid, hydroxymethylphosphonic acid and phosphonoformic acid by blocked mutants of Streptomyces hygroscopicus SF-1293 and their roles in the biosynthesis of bialaphos.

Organic Phosphorus Compounds. 55. The direct synthesis of hydroxymethylphosphonic acid, bis(hydroxymethyl)phosphinic acid, and methyl(hydroxymethyl)phosphinic acid

AbstractThe interaction of white phosphorus and formaldehyde in water/methanol in the presence of a base is described. A mechanism accounting for the formation of HOCH2PO3H2, (HOCH2)2PO2H and CH3(HOCH2)PO2H is proposed. Chlorination of these products to give ClCH2P(O)Cl2, (ClCH2)2P(O)Cl, and CH3(ClCH2)P(O)Cl is also reported.

Reaction of hydroxymethylphosphonic acids and their esters with isocyanates

1. The authors have studied the reaction of α-hydroxymethylphosphonous acid, dimethylolphosphonous acid and its sodium salt with mono- and diisocyanates. 2. The hydroxyl groups on the α-carbon atoms react like ordinary alcoholic hydroxyl groups, giving carbamic esters of the corresponding acids; the hydroxyl group on the phosphorus atom acts like a strongly acid group, giving the acid amide. 3. Hardening of dimethylolphosphonous acid-based polyesters gives insoluble and infusible polymers.

Synthesis and properties of hydroxymethylphosphonic and bishydroxymethylphosphinic acids

By the reaction of phosphorous acid and its salts and of hypophosphorous salts with paraform, hydroxymethylphosphonic acid and its salts and bishydroxymethylphosphinic salts were obtained in 90–93% yield.

Bromomagnesium Salts of Dialkyl Phosphites as Intermediates in the Synthesis of Substituted Hydroxymethyl Phosphonic Acid Esters

Bromomagnesium Salts of Dialkyl Phosphites as Intermediates in the Synthesis of Substituted Hydroxymethyl Phosphonic Acid Esters