Phosphorus-31 Nuclear Magnetic Resonance Spectroscopy Research Articles

A versatile, highly effective intumescent flame-retardant synergist for polypropylene and polyamide 6 composites

A novel phosphorus-based macromolecular flame-retardant synergist named DPS was designed and synthesized via three steps from 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO), dihydroxybenzophenone (DHBP) and pentaerythritol (PER). The prepared synergist was used in combination with a base flame-retardant (melamine-coated ammonium polyphosphate (APP-M), or aluminum diethylphosphinate (ADP)) to create novel binary intumescent flame retardant (IFR) systems for polypropylene (PP) and polyamide 6 (PA6) matrices. The structure of DPS was characterized by fourier transform infrared (FTIR), phosphorus nuclear magnetic resonance spectroscopy (31P NMR) and gel permeation chromatography (GPC) analysis. The thermal stability and combustion behaviors of the flame-retardant polymer composites were investigated by thermogravimetric analysis (TGA), limiting oxygen index (LOI), UL-94 vertical burning tests. It was found that with a low fraction of DPS (20–25 wt%), the developed binary IFR systems significantly enhanced the flame-retardant performance of both PP and PA6. The results indicate that owing to the rich phosphorus content and abundant aromatic structures, DPS has synergistic actions with the base flame retardants to scavenge free radicals and promote char formation in the gaseous and condensed phases, respectively. Additionally, the mechanical properties of the PP composites were also evaluated, revealing the mechanical reinforcement effect of the binary IFR, i.e., simultaneous improvement of tensile modulus, ultimate tensile strength and impact toughness. This further demonstrates the effectiveness of the developed IFR formulations in terms of well-balanced flame-retardant performance and mechanical properties.

Studying the Suitability of Nineteen Lignins as Partial Polyol Replacement in Rigid Polyurethane/Polyisocyanurate Foam.

In this study, nineteen unmodified lignins from various sources (hardwood, softwood, wheat straw, and corn stover) and isolation processes (kraft, soda, organosolv, sulfite, and enzymatic hydrolysis) were used to replace 30 wt.% of petroleum-based polyol in rigid polyurethane/polyisocyanurate (PUR/PIR) foam formulations. Lignin samples were characterized by measuring their ash content, hydroxyl content (Phosphorus Nuclear Magnetic Resonance Spectroscopy), impurities (Inductively Coupled Plasma), and pH. After foam formulation, properties of lignin-based foams were evaluated and compared with a control foam (with no lignin) via cell morphology, closed-cell content, compression strength, apparent density, thermal conductivity, and color analysis. Lignin-based foams passed all measured standard specifications required by ASTM International C1029-15 for type 1 rigid insulation foams, except for three foams. These three foams had poor compressive strengths, significantly larger cell sizes, darker color, lower closed-cell contents, and slower foaming times. The foam made with corn stover enzymatic hydrolysis lignin showed no significant difference from the control foam in terms of compressive strength and outperformed all other lignin-based foams due to its higher aliphatic and p-hydroxyphenyl hydroxyl contents. Lignin-based foams that passed all required performance testing were made with lignins having higher pH, potassium, sodium, calcium, magnesium, and aliphatic/p-hydroxyphenyl hydroxyl group contents than those that failed.

Characteristics and distribution of phosphorus in surface sediments of a shallow lake

Phosphorus (P) in sediments plays an important role in shallow lake ecosystems and has a major effect on the lake environment. The mobility and bioavailability of P primarily depend on the contents of different P forms, which in turn depend on the sedimentary environment. Here, sediment samples from Baiyangdian (BYD) lake were collected and measured by the Standards, Measurements, and Testing procedure and Phosphorus-31 nuclear magnetic resonance spectroscopy (31P NMR) to characterize different P forms and their relationships with sediment physicochemical properties. The P content in the sediments varied in different areas and had characteristics indicative of exogenous river input. Inorganic P (334–916 mg/kg) was the dominant form of P. The 31P NMR results demonstrated that orthophosphate monoesters (16–110 mg/kg), which may be a source of P when redox conditions change, was the dominant form of organic P (20–305 mg/kg). The distribution of P forms in each region varied greatly because of the effects of anthropogenic activities, and the regions affected by exogenous river input had a higher content of P and a higher risk of P release. Principal component analysis indicated that P bound to Fe, Al, and Mn oxides and hydroxides (NaOH-P) and organic P were mainly derived from industrial and agricultural pollution, respectively. Redundancy analysis indicated that increases in pH lead to the release of NaOH-P. Organic matter plays an important role in the organic P biogeochemical cycle, as it acts as a sink and source of organic P.

Evaluating efficacy of different UV-stabilizers/absorbers in reducing UV-degradation of lignin

Abstract Susceptibility of wood to UV degradation decreases the service life of wood products outdoors. Organic UV absorbers (UVAs) and hindered amine light stabilizers (HALSs), as well as inorganic UVAs, are added to coatings to improve the UV stability of coated-wood products. Although about 85% of UV radiation is absorbed by lignin in the wood, it is unclear which UV stabilizers can minimize lignin degradation. In this study, the photodegradation of softwood organosolv lignin was monitored over 35 days of UV exposure. Changes in lignin properties were assessed using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), gel permeation chromatography (GPC), and phosphorus-31 nuclear magnetic resonance spectroscopy (31P NMR). It was found that the aromatic rings of lignin underwent significant degradation, resulting in increased glass transition temperature and molecular weight of lignin. Subsequently, 18 different additives were mixed with lignin and exposed to UV irradiation. The analysis of samples before and after UV exposure with FTIR revealed that inorganic UVAs (cerium oxide and zinc oxide) and a mixture of organic UVAs and HALSs (T-479/T-292, T-5248, and T-5333) were the most effective additives in reducing lignin degradation. This study can help coating scientists to formulate more durable transparent exterior wood coatings.

Factors Affecting the Sensitivity of Hydroxyl Group Content Analysis of Biocrude Products via Phosphitylation and 31P NMR Spectroscopy

A useful method for quantifying concentrations of various hydroxyl group containing molecular species in biocrudes involves chemically converting species into nonionizable, P-functionalized derivatives independently observed and quantified by phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy. Full validation of this method requires improved understanding of its applicability to different biocrude matrixes. The limits of detection (LODs) and limits of quantitation (LOQs) for this method are herein determined for concentrations of hydroxyl group containing analytes, grouped by molecular class, within three different biocrude matrixes: a biocrude (BC) product, a fast pyrolysis (FP) product, and an artificial matrix (AM). Matrix water content, known to affect method sensitivity, varies from <1 to 18.31 wt %. Each matrix is used to prepare a series of samples spiked to varying concentrations with three hydroxyl group containing model compounds, which represent (aliphatic) alcohol, phenolic, and carboxylic acid analyte types. Samples are then phosphitylated with 2-chloro-4,4,5,5-tetramethyl-1,3,2-dioxaphospholane to enable 31P NMR spectroscopic determination of native hydroxyl analyte concentrations. LODs and LOQs are determined for each analyte type and for each matrix. Analytical precision is affected by matrix concentrations of interfering analytes and water. Among the matrixes examined, AM, which contains no hydroxyl analytes and has the lowest water content, expectedly exhibits the lowest LODs and LOQs. Matrix LODs range from 0.04 to 0.14 mmol of OH/g, while their LOQs range from 0.10 to 0.41 mmol of OH/g, with both sets of values generally increasing in the order AM < BC < FP.

Value-added utilization of lignin-derived aromatic oligomers as renewable charge-storage materials

Lignin-derived aromatic oligomers (LDAOs) are the primary components of lignin depolymerization products. They are typically utilized as renewable crosslinking agents or resin materials with a considerably lower application value than aromatic monomers. Notably, LDAOs are rich in quinone groups, which enable storage and release of charges. In this work, the feasibility of LDAOs as renewable charge storage materials was investigated. LDAOs were first reacted with formaldehyde to generate a synthetic polymer (SP-AOF) via a phenol-formaldehyde condensation reaction. SP-AOF was subsequently incorporated with reduced graphene oxide (rGO), namely rGO/SP-AOF. As expected, the hybrid electrode exhibited high specific capacitance (250 F/g), which was approximately three times higher than that of rGO (87 F/g). This was due to the presence of quinone groups in SP-AOF, which could contribute to the overall capacitance with pseudocapacitance. Moreover, the hybrid electrode was able to deliver a high specific capacitance of 210 F/g even at a high specific current of 10 A/g. 1H−13C heteronuclear single quantum coherence nuclear magnetic resonance (2D HSQC NMR) and phosphorus nuclear magnetic resonance spectroscopy (31P NMR) analyses revealed that SP-AOF displayed higher quinone content (3.76 mmol/g) than commercially available lignin (organosolv and alkali lignin), which resulted in higher energy storage performance. This study provides a promising strategy for the utilization of aromatic oligomers as raw materials to manufacture high-performance lignin-derived energy storage materials.

Aberrant sphingomyelin 31P-NMR signatures in giant cell tumour of bone.

An understanding of the biochemistry of the giant cell tumour of bone (GCTB) provides an opportunity for the development of prognostic markers and identification of therapeutic targets. Based on metabolomic analysis, we proposed glycerophospholipid metabolism as the altered pathway in GCTB., The objective of this study was to identify these altered metabolites. Using phosphorus-31 nuclear magnetic resonance spectroscopy (31P-NMR), sphingomyelin was determined to be the most dysregulated phospholipid in tissue samples from six patients with GCTB. Enzymes related to its biosynthesis and hydrolysis were examined using immunodetection techniques. High expression of sphingomyelin synthases 1 and 2, but low expression of neutral sphingomyelinase 2 (nSMase2) was found in GCTB tissues compared to non-neoplastic bone tissues. Sphingomyelin/ceramide biosynthesis is dysregulated in GCTB due to alterations in the expression of SMS1, SMS2, and nSMase2.

Lignin as a Partial Polyol Replacement in Polyurethane Flexible Foam.

This study was focused on evaluating the suitability of a wide range of lignins, a natural polymer isolated from different plant sources and chemical extractions, in replacing 20 wt.% of petroleum-based polyol in the formulation of PU flexible foams. The main goal was to investigate the effect of unmodified lignin incorporation on the foam’s structural, mechanical, and thermal properties. The hydroxyl contents of the commercial lignins were measured using phosphorus nuclear magnetic resonance (31P NMR) spectroscopy, molar mass distributions with gel permeation chromatography (GPC), and thermal properties with differential scanning calorimetry (DSC) techniques. The results showed that incorporating 20 wt.% lignin increased tensile, compression, tear propagation strengths, thermal stability, and the support factor of the developed PU flexible foams. Additionally, statistical analysis of the results showed that foam properties such as density and compression force deflection were positively correlated with lignin’s total hydroxyl content. Studying correlations between lignin properties and the performance of the developed lignin-based PU foams showed that lignins with low hydroxyl content, high flexibility (low Tg), and high solubility in the co-polyol are better candidates for partially substituting petroleum-based polyols in the formulation of flexible PU foams intended for the automotive applications.

Contribution to understanding the color development on wood surfaces treated with iron salts by a combination of analytical methods

Metal salts application on wood surface is a simple and nontoxic method that can be used for wood color modification, which is induced by the formation of colored complexes between wood extractives and metal ions. In this study, we have combined several analytical methods to understand the color development for four North American hardwood species: white oak, red oak, sugar maple and yellow birch. The phenolic composition of the ethanolic extracts of heartwood and sapwood of the four wood species was studied by UV-Vis spectrometry and liquid state phosphorus-31 nuclear magnetic resonance spectroscopy (31P NMR) and analyzed in relation to color development. The correlations between different OH types and the color development as measured with the CIEL*a*b* color coordinates, indicate that the descending order of correlation for phenolic hydroxyls was: di-substituted OH, mono-substituted OH and un-substituted OH while no correlation was found between COOH hydroxyls and total color change (ΔE).

Phytic acid-based flame retardants for cotton

Development of sustainable flame retardants for cotton-based materials has become an active research interest as many of the currently used flame retardants are harmful both to the environment and to human health. Phytic acid is a natural resource that has shown potential to be an environment-friendly flame retardant. In order to design highly efficient flame retardants based on phytic acid, detailed knowledge of the decomposition process is essential. In this study, cotton samples were prepared with pure phytic acid, as well as salts of sodium or calcium ions. All samples improved the fire performance, most notably sodium phytate, as shown by a simple burning test, as well as by thermogravimetric analysis. The formation of char prevents the degradation of cotton, leaving a residual mass. Phosphorus-31 nuclear magnetic resonance spectroscopy was used to characterize the intermediate products formed during the pyrolysis process. Both phytate salts polymerize, sodium to a higher degree than calcium.

Structural basis for stabilization of human telomeric G-quadruplex [d-(TTAGGGT)]4 by anticancer drug adriamycin

Besides inhibiting DNA duplication, DNA dependent RNA synthesis and topoisomerase-II enzyme action, anticancer drug adriamycin is found to cause telomere dysfunction and shows multiple strategies of action on gene functioning. We present evidence of binding of adriamycin to parallel stranded intermolecular [d-(TTAGGGT)]4 G-quadruplex DNA comprising human telomeric DNA by proton and phosphorus-31 nuclear magnetic resonance spectroscopy. Diffusion ordered spectroscopy shows formation of complex between the two molecules. Changes in chemical shift and line broadening of DNA and adriamycin protons suggest participation of specific chemical groups/moieties in interaction. Presence of sequential nuclear Overhauser enhancements at all base quartet steps and absence of large downfield shifts in 31P resonances give clear proof of absence of intercalation of adriamycin chromophore between base quartets. Restrained molecular dynamics simulations using observed 15 short intermolecular inter proton distance contacts depict stacking of ring D of adriamycin with terminal G6 quartet by displacing T7 base and external groove binding close to T1–T2–A3 bases. The disappearance of imino protons monitored as a function of temperature and differential scanning calorimetry experiments yield thermal stabilization of 24 °C, which is likely to come in the way of telomerase association with telomeres. The findings pave the way for design of alternate anthracycline based drugs with specific modifications at ring D to enhance induced thermal stabilization and use alternate mechanism of binding to G-quadruplex DNA for interference in functional pathway of telomere maintenance by telomerase enzyme besides their well known action on duplex DNA. Communicated by Ramaswamy H. Sarma

Inorganic phosphate, protons and diprotonated phosphate may contribute to the exacerbated muscle fatigue in older adults

Inorganic phosphate, protons and diprotonated phosphate may contribute to the exacerbated muscle fatigue in older adults

Transformation of soil organic phosphorus along the Hailuogou post-glacial chronosequence, southeastern edge of the Tibetan Plateau

Organic phosphorus (P) accumulates in soil during pedogenesis, yet information on the composition and transformation of organic P during the early stages of soil development remains scarce. We studied the top 5 cm of mineral soil immediately beneath the organic horizon from six sites (0, 35, 45, 57, 85 and 125 years) along the Hailuogou glacier foreland chronosequence, on the southeastern edge of the Tibetan Plateau. Phosphorus compounds in the soils were determined by NaOH–EDTA extraction and solution phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy. Extractable P was dominated by phosphomonoesters (up to 51.5%) and orthophosphate (37.9–44.6%) throughout the chronosequence. The phosphomonoesters were mainly hydrolysis products of RNA and phospholipids and followed a unimodal pattern with soil age, with maximum concentration at the 57-year-old site. myo-Inositol hexakisphosphate was not detected, although scyllo-inositol hexakisphosphate accounted for 4.7–9.3% of the extracted P and d-chiro- and neo-inositol hexakisphosphates occurred small amounts in a few soils (1.1–3.3% of the extracted P). DNA accounted for 4.0–8.3% of extracted P and increased continuously along the chronosequence, associated with increased inputs of plant and microbial residues and stronger sorption to soil surfaces during the rapid decline in soil pH. Pyrophosphate, an inorganic polyphosphate, occurred in small concentrations (up to 5.0%) that fluctuated with soil age. We conclude that organic P compounds accumulate rapidly in the top mineral soil during the early stages of pedogenesis, predominantly as relatively labile compounds from plant and microbial residues.

Bioenergetic basis for the increased fatigability with ageing.

The mechanisms for the age-related increase in fatigability during dynamic exercise remain elusive. We tested whether age-related impairments in muscle oxidative capacity would result in a greater accumulation of fatigue causing metabolites, inorganic phosphate (Pi ), hydrogen (H+ ) and diprotonated phosphate (H2 PO4- ), in the muscle of old compared to young adults during a dynamic knee extension exercise. The age-related increase in fatigability (reduction in mechanical power) of the knee extensors was closely associated with a greater accumulation of metabolites within the working muscle but could not be explained by age-related differences in muscle oxidative capacity. These data suggest that the increased fatigability in old adults during dynamic exercise is primarily determined by age-related impairments in skeletal muscle bioenergetics that result in a greater accumulation of metabolites. The present study aimed to determine whether the increased fatigability in old adults during dynamic exercise is associated with age-related differences in skeletal muscle bioenergetics. Phosphorus nuclear magnetic resonance spectroscopy was used to quantify concentrations of high-energy phosphates and pH in the knee extensors of seven young (22.7±1.2years; six women) and eight old adults (76.4±6.0years; seven women). Muscle oxidative capacity was measured from the phosphocreatine (PCr) recovery kinetics following a 24s maximal voluntary isometric contraction. The fatiguing exercise consisted of 120 maximal velocity contractions (one contraction per 2s) against a load equivalent to 20% of the maximal voluntary isometric contraction. The PCr recovery kinetics did not differ between young and old adults (0.023±0.007s-1 vs. 0.019±0.004s-1 , respectively). Fatigability (reductions in mechanical power) of the knee extensors was ∼1.8-fold greater with age and was accompanied by a greater decrease in pH (young=6.73±0.09, old=6.61±0.04) and increases in concentrations of inorganic phosphate, [Pi ], (young=22.7±4.8mm, old=32.3±3.6mm) and diprotonated phosphate, [H2 PO4- ], (young=11.7±3.6mm, old=18.6±2.1mm) at the end of the exercise in old compared to young adults. The age-related increase in power loss during the fatiguing exercise was strongly associated with intracellular pH (r=-0.837), [Pi ] (r=0.917) and [H2 PO4- ] (r=0.930) at the end of the exercise. These data suggest that the age-related increase in fatigability during dynamic exercise has a bioenergetic basis and is explained by an increased accumulation of metabolites within the muscle.

Minocycline-loaded calcium polyphosphate glass microspheres as a potential drug-delivery agent for the treatment of periodontitis.

Background: Periodontitis is an inflammatory disease with a bacterial etiology that affects the supporting structures of the teeth and is a major cause of tooth loss. The objective of this study was to investigate the drug loading and in vitro release of minocycline from novel calcium polyphosphate microspheres intended for use in treating periodontitis. Methods: Calcium polyphosphate coacervate, produced by a precipitation reaction of calcium chloride and sodium polyphosphate solutions, was loaded with minocycline and subsequently used to produce microspheres by an emulsion/solvent extraction technique. Microspheres classified by size were subjected to a 7-day elution in a Tris-buffer solution under dynamic conditions. The physicochemical characteristics of the drug-loaded microspheres were investigated using scanning electron microscopy, particle size analysis, Phosphorus-31 Nuclear Magnetic Resonance spectroscopy, and Inductively Coupled Plasma Optical Emission Spectroscopy. Drug loading and release were determined using ultraviolet -visible (UV/VIS) spectrophotometry. Results: Minocycline-loaded calcium polyphosphate microspheres of varying size were successfully produced, with small and large microspheres having volume mean diameters of 22 ± 1 µm and 193 ± 5 µm, respectively. Polyphosphate chain length and calcium to phosphorus mole ratio remained stable throughout microsphere production. Drug loading was 1.64 ± 0.16, 1.35 ± 0.55, and 0.84 ± 0.14 weight% for the coacervate and large and small microspheres, respectively, corresponding to mean encapsulation efficiencies of 81.7 ± 12.2 % and 50.9 ± 3.9 % for the large and small microspheres. Sustained drug release was observed in vitro over a clinically relevant 7-day period, with small and large microspheres exhibiting similar elution profiles. Antibiotic release generally followed microsphere degradation as measured by Ca and P ion release. Conclusions: This study demonstrated successful drug loading of calcium polyphosphate microspheres with minocycline. Furthermore, in vitro sustained release of minocycline over a 7-day period was observed, suggesting potential utility of this approach for treating periodontitis.

Effects of altered pyruvate dehydrogenase activity on contracting skeletal muscle bioenergetics.

During aerobic exercise (>65% of maximum oxygen consumption), the primary source of acetyl-CoA to fuel oxidative ATP synthesis in muscle is the pyruvate dehydrogenase (PDH) reaction. This study investigated how regulation of PDH activity affects muscle energetics by determining whether activation of PDH with dichloroacetate (DCA) alters the dynamics of the phosphate potential of rat gastrocnemius muscle during contraction. Twitch contractions were induced in vivo over a broad range of intensities to sample submaximal and maximal aerobic workloads. Muscle phosphorus metabolites were measured in vivo before and after DCA treatment by phosphorus nuclear magnetic resonance spectroscopy. At rest, DCA increased PDH activation compared with control (90 ± 12% vs. 23 ± 3%, P < 0.05), with parallel decreases in inorganic phosphate (Pi) of 17% (1.4 ± 0.2 vs. 1.7 ± 0.1 mM, P < 0.05) and an increase in the free energy of ATP hydrolysis (ΔGATP) (-66.2 ± 0.3 vs. -65.6 ± 0.2 kJ/mol, P < 0.05). During stimulation DCA increased steady-state phosphocreatine (PCr) and the magnitude of ΔGATP, with concomitant reduction in Pi and ADP concentrations. These effects were not due to kinetic alterations in PCr hydrolysis, resynthesis, or glycolytic ATP production and altered the flow-force relationship between mitochondrial ATP synthesis rate and ΔGATP. DCA had no significant effect at 1.0- to 2.0-Hz stimulation because physiological mechanisms at these high stimulation levels cause maximal activation of PDH. These data support a role of PDH activation in the regulation of the energetic steady state by altering the phosphate potential (ΔGATP) at rest and during contraction.

Molecular Recognition of Parallel G-quadruplex [d-(TTGGGGT)]₄ Containing Tetrahymena Telomeric DNA Sequence by Anticancer Drug Daunomycin: NMR-Based Structure and Thermal Stability.

The anticancer drug daunomycin exerts its influence by multiple strategies of action to interfere with gene functioning. Besides inhibiting DNA/RNA synthesis and topoisomerase-II, it affects the functional pathway of telomere maintenance by the telomerase enzyme. We present evidence of the binding of daunomycin to parallel-stranded tetramolecular [d-(TTGGGGT)]4 guanine (G)-quadruplex DNA comprising telomeric DNA from Tetrahymena thermophilia by surface plasmon resonance and Diffusion Ordered SpectroscopY (DOSY). Circular Dichroism (CD) spectra show the disruption of daunomycin dimers, suggesting the end-stacking and groove-binding of the daunomycin monomer. Proton and phosphorus-31 Nuclear Magnetic Resonance (NMR) spectroscopy show a sequence-specific interaction and a clear proof of absence of intercalation of the daunomycin chromophore between base quartets or stacking between G-quadruplexes. Restrained molecular dynamics simulations using observed short interproton distance contacts depict interaction at the molecular level. The interactions involving ring A and daunosamine protons, the stacking of an aromatic ring of daunomycin with a terminal G6 quartet by displacing the T7 base, and external groove-binding close to the T1–T2 bases lead to the thermal stabilization of 15 °C, which is likely to inhibit the association of telomerase with telomeres. The findings have implications in the structure-based designing of anthracycline drugs as potent telomerase inhibitors.

Modifying cellulose with metaphosphoric acid and its efficiency in removing brilliant green dye

In this study, cellulose was chemically modified through the addition of the phosphorylating agent, metaphosphoric acid in order to obtain a new material (MPCel) with higher adsorptive properties than the starting material. Both materials were characterized by infrared spectroscopy, X-ray diffraction, solid-state phosphorus-31 nuclear magnetic resonance spectroscopy and thermogravimetric analysis. Maximal adsorption capacity, at 45°C for pure cellulose, was 90.5mgg−1, at pH=10 and contact time of 40min, with experimental isotherms better adjusted to the Langmuir model. MPCel at the same temperature conditions showed contact time of 10min, pH=10, and maximal adsorption capacity of 150.0mgg−1, being better adjusted to the Temkin model. The kinetic study of both materials followed the pseudo-second-order model. Modification successfully occurred and both adsorbents were shown able to be capable of removing the brilliant green dye, but MPCel was more efficient for purpose, when compared to the pure cellulose.

In vivo and in vitro 31P-NMR Study of the Phosphate Transport and Polyphosphate Metabolism in Hebeloma cylindrosporum in Response to Plant Roots Signals.

We used in vivo and in vitro phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy to follow the change in transport, compartmentation and metabolism of phosphate in the ectomycorrhizal fungus Hebeloma cylindrosporum in response to root signals originating from host (Pinus pinaster) or non-host (Zea mays) plants. A device was developed for the in vivo studies allowing the circulation of a continuously oxygenated mineral solution in an NMR tube containing the mycelia. The in vitro studies were performed on fungal material after several consecutive treatment steps (freezing in liquid nitrogen; crushing with perchloric acid; elimination of perchloric acid; freeze-drying; dissolution in an appropriate liquid medium).

Improved oral bioavailability and therapeutic efficacy of erlotinib through molecular complexation with phospholipid

The current study was aimed to prepare a molecular complex of erlotinib (ERL) with phospholipid (PC) for enhancement of solubility and thus bioavailability, therapeutic efficacy and reducing the toxicity of erlotinib. Phospholipid complex of drug was prepared by solvent evaporation method and characterized by differential scanning calorimetry (DSC), Fourier transform infra-red spectroscopy (FT-IR), proton and phosphorus nuclear magnetic resonance spectroscopy (1H NMR and 31P NMR), powder X-ray diffraction (P-XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), which all explained the interactions of two components, validating the complexation phenomenon. In silico study also supported the phase change and molecular interactions for the establishment of ERL-PC. Spherical shaped nanostructures with 183.37±28.61nm size, −19.52±6.94mV potential and 28.59±2.66% loading efficiency were formed following dispersion of ERL-PC in aqueous media. In vitro release study revealed the higher release of ERL-PC due to amorphization and solubilization of drug. Caco-2 cell uptake resulted in ∼2 fold higher uptake of ERL-PC than free drug. In vitro cell culture studies were performed using human pancreatic adenocarcinoma cell lines, which demonstrated the higher cytotoxicity and apoptosis in case of ERL-PC. In vivo pharmacokinetics also supported the in vitro observations and showed ∼1.7 fold higher bioavailability with ERL-PC than ERL. Finally, in vivo efficacy and toxicity studies explained the superiority of ERL-PC over the free drug. Based on the results, phospholipid complex appears to be a promising tool to enhance bioavailability, efficacy, cytotoxicity and safety of erlotinib.