Phosphorous pentoxide-free bioactive glass exhibits dose-dependent angiogenic and osteogenic capacities which are retained in glass polymeric composite scaffolds.

Bioactive glasses (BGs) are attractive materials for bone tissue engineering because of their bioactivity and osteoinductivity. In this study, we report the synthesis of a novel phosphorous pentoxide-free, silicate-based bioactive glass (52S-BG) composed of 52.1% SiO2, 23.2% Na2O and 22.6% CaO (wt%). The glass was thoroughly characterized. The biocompatibility and osteogenic properties of 52S-BG particles were analyzed in vitro with human adipose-derived mesenchymal stem cells (AdMSCs) and human osteoblasts. 52S-BG particles were biocompatible and induced mineralized matrix deposition and the expression of osteogenic markers (RunX2, alkaline phosphatase, osteocalcin, osteopontin, collagen I) and the angiogenic marker vascular endothelial growth factor (VEGF). Angiogenic properties were additionally confirmed in a zebrafish embryo model. 52S-BG was added to poly-ε-caprolactone (PCL) to obtain a composite with 10 wt% glass content. Composite PCL/52S-BG scaffolds were fabricated by additive manufacturing and displayed high porosity (76%) and pore interconnectivity. The incorporation of 52S-BG particles increased the Young's modulus of PCL scaffolds from 180 to 230 MPa. AdMSC seeding efficiency and proliferation were higher in PCL/52S-BG compared to PCL scaffolds, indicating improved biocompatibility. Finally, 52S-BG incorporation improved the scaffolds' osteogenic and angiogenic properties by increasing mineral deposition and inducing relevant gene expression and VEGF protein secretion. Overall, 52S-BG particles and PCL/52S-BG composites may be attractive for diverse bone engineering applications requiring concomitant angiogenic properties.

Pnictogens in medicinal chemistry: evolution from erstwhile drugs to emerging layered photonic nanomedicine.

Pnictogens (the non-metal phosphorus, metalloids arsenic and antimony, and metal bismuth) possess diverse chemical characteristics that support the formation of extended molecular structures. As witnessed by the centuries-old (and ongoing) clinical utilities, pnictogen-based compounds have secured their places in history as "magic bullet" therapeutic drugs in medicinal contexts. Moreover, with the development of recent metalloproteomics and bio-coordination chemistry, the pnictogen-based drugs functionally binding to proteins/enzymes in biological systems have been underlaid for "drug repurposing" with promising opportunities. Furthermore, advances in the modern materials science and nonotechnology have stimulated a revolution in other newly discovered forms of pnictogens-phosphorene, arsenene, antimonene, and bismuthine (layered pnictogens). Based on their favorable optoelectronic properties, layered pnictogens have shown dramatic superiority as emerging photonic nanomedicines for the treatment of various diseases. This tutorial review outlines the history and mechanism of action of ancient pnictogen-based drugs (e.g., arsenical compounds in traditional Chinese medicine) and their repurposing into modern therapeutics. Then, the revolutionary use of emerging layered pnictogens as photonic nanomedicines, alongside assessments of their in vivo biosafety, is discussed. Finally, the challenges to further development of pnictogens are set forth and insights for further exploration of their appealing properties are offered. This tutorial review may also provide some deep insights into the fields of integrated traditional Chinese and Western medicines from the perspective of materials science and nanotechnology.

Agronomic efficiency and profitability of cotton on integrated use of phosphorus and plant microbes / Eficiência e rentabilidade agronômica do algodão no uso integrado de fósforo e micróbios vegetais

Cotton crop, plays a significant role in Pakistan's economy by ruling a prominent place in edible oil and local textile industry. Phosphorus (P) inaccessibility and deficiency of soil organic matter are the key restraints for low crop productivity in cotton. Therefore, a two years field study was designed during 2014-15, to explore the influence of phosphate solubilizing bacteria (PSB), farmyard manure (FYM), poultry manure (PM) and inanimate sources of P on various physiological, growth, yield and quality parameters of cotton crop at CCRI Multan. Field responses of seeds inoculated with two distinctive phosphate solubilizing bacteria (PSB) strains viz. S0 = control, S1 =strain-1, S2 = strain-2 and eight organic, inorganic P sources viz., P0= control, P1 = 80 kg ha-1 P from inorganic source, P2 = 80 kg ha-1 P from FYM, P3 = 80 kg ha-1 P from PM, P4 = 40 kg ha-1 P from FYM + 40 kg ha-1 P from inorganic source, P5 = 40 kg ha-1 P from PM + 40 kg ha-1 P from inorganic source, P6 = 80 kg ha-1 P from FYM + 40 kg ha-1 P from inorganic source, P7 = 80 kg ha-1 P from PM + 40 kg ha-1 P from inorganic source and P8 = 40 kg ha-1 P from FYM + 40 kg ha-1 P from PM were evaluated. Results revealed that inoculation of seeds with PSB and collective use of inorganic and organic sources of P had considerably increased the yield contributing attributes in cotton. However, the treatment P7 (80 kg P ha-1 from PM + 40 kg P ha-1 from inorganic source) in coincidence with seeds inoculated with PSB (S1) produced taller plant, maximum boll weight, significantly higher LAI and CGR. Significantly higher seed cotton yield, lint yield, fiber length and maximum BCR of 1.95 and 1.81 was also obtained from the P7 treatment during both crop-growing seasons. In conclusion, combined use of 80 kg P ha-1 from PM + 40 kg P ha-1 from inorganic source and cotton seeds inoculated with strain-1 improved phosphorus uptake ensuing in greater consumption of photo-assimilates for maximum growth and yield.

A safra de algodão, desempenha um papel significativo na economia do Paquistão, ao ocupar um lugar de destaque no óleo comestível e na indústria têxtil local. A inacessibilidade e a deficiência de fósforo (P) da matéria orgânica do solo são as principais restrições para a baixa produtividade das culturas em algodão. Portanto, um estudo de campo de dois anos foi desenvolvido durante 2014-15, para explorar a influência de bactérias solubilizantes de fosfato (PSB), esterco de capoeira (FYM), esterco de aves (PM) e fontes inanimadas de P sobre vários fatores fisiológicos, crescimento, rendimento e parâmetros de qualidade da cultura do algodão no CCRI Multan. Respostas de campo de sementes inoculadas com duas cepas distintas de bactérias solubilizantes de fosfato (PSB) viz. S0 = controle, S1 = cepa-1, S2 = cepa-2 e oito fontes orgânicas de P inorgânicas viz., P0 = controle, P1 = 80 kg ha-1 P de fonte inorgânica, P2 = 80 kg ha-1 P de FYM, P3 = 80 kg ha-1 P de PM, P4 = 40 kg ha-1 P de FYM + 40 kg ha-1 P de fonte inorgânica, P5 = 40 kg ha-1 P de PM + 40 kg ha-1 P de fonte inorgânica, P6 = 80 kg ha-1 P de FYM + 40 kg ha-1 P de fonte inorgânica, P7 = 80 kg ha-1 P de PM + 40 kg ha-1 P de fonte inorgânica e P8 = 40 Foram avaliados kg ha-1 P da FYM + 40 kg ha-1 P da PM. Os resultados revelaram que a inoculação de sementes com PSB e o uso coletivo de fontes inorgânicas e orgânicas de P aumentaram consideravelmente os atributos que contribuem para a produtividade no algodão. No entanto, o tratamento P7 (80 kg P ha-1 da PM + 40 kg P ha-1 da fonte inorgânica) em coincidência com sementes inoculadas com PSB (S1) produziu planta mais alta, peso máximo de cápsula, IAF e CGR significativamente maiores. Produtividade significativamente maior do algodão, rendimento de fiapos, comprimento da fibra e BCR máximo de 1,95 e 1,81 também foi obtida a partir do tratamento P7 durante as duas épocas de cultivo. Em conclusão, o uso combinado de 80 kg P ha-1 de PM + 40 kg P ha-1 de fonte inorgânica e sementes de algodão inoculadas com a cepa-1 melhoraram a captação de fósforo, resultando em maior consumo de foto assimilados para obter crescimento e produtividade máximos.

Enzyme-instructed self-assembly of the stereoisomers of pentapeptides to form biocompatible supramolecular hydrogels.

This article reports enzyme-instructed self-assembly (EISA) of stereoisomers of pentapeptides as a simple approach for generating biocompatible supramolecular hydrogels as potential soft bionanomaterials. Peptide-based supramolecular hydrogels are emerging as a new type of biomaterials. The use of tyrosine phosphate offers a trigger for enzymatic hydrogelation, and the incorporation of D-amino acids can increase the proteolytic stability of peptides. This work compared four phosphorpeptides that are stereoisomers in terms of rate of dephosphorylation, proteolytic stability, and cell compatibility. The results show that the naphthyl (Nap)-capped pentapeptides, containing the amino acid sequence of Phe-Phe-Gly-Glu-pTyr, are able to undergo EISA to form the hydrogels consisting the nanofibres of the dephosphorylated pentapeptides. The naphthyl-capped D-phosphopentpeptides, contrasting to a naphthyl-capped D-phosphotripeptide (Nap-D-Phe-D-Phe-D-pTyr), are largely cell compatible. This result, suggesting that the sequence of phophopeptides also dedicates the cell compatibility of the peptide assemblies resulted from EISA, provides useful insights for developing supramolecular hydrogels as potential biomaterials with tailored properties.

Bioorthogonal Phosphorogenic Rhenium(I) Polypyridine Sydnone Complexes for Specific Lysosome Labeling.

Invited for this month's cover is the group of Prof. Kenneth Kam-Wing Lo at City University of Hong Kong, Hong Kong, P. R. China. The cover picture shows the selective landing of a bioorthogonal spacecraft on a lysosomal planet modified with a strained cyclooctyne moiety in an intracellular environment with other organelles and a plethora of biomolecules. A sydnone moiety is appended to a luminescent rhenium(I) diimine unit as both an emission quencher and a bioorthogonal handle. Selective strain-promoted sydnone-alkyne cycloaddition (SPSAC) of the complex with a strained alkyne leads to impressive emission turn-on, which can be exploited in bioimaging and phototherapeutic applications. Read the full text of the article at 10.1002/cplu.202000029.

The role of CaO/SiO2 ratio and P2O5 content in gel-derived bioactive glass-polymer composites in the modulation of their bioactivity and osteoinductivity in human BMSCs.

We obtained a range of PLGA-based composites containing sol-gel bioactive glasses (SBG) from the SiO2-CaO and SiO2-CaO-P2O5 systems. Eight SBGs with different CaO/SiO2 ratios with and without P2O5 were incorporated at 50% w/w to PLGA matrix and structured into thin films suitable for cell culture. The SBG/PLGA composites were examined for their bioactivity in simulated body fluid (SBF), ion release profile in culture media with and without cells, and osteoinductivity in standard human bone marrow stromal cell (hBMSC) cultures without osteogenic growth factors. Our results indicate different surface activity of composites depending on the presence/absence of P2O5 in SBG composition. Furthermore, ion release profile to culture medium differed depending on the presence/absence of cells. Direct culture of hBMSC on the SiO2-CaO/PLGA composite films resulted in elevated Runx-2 mRNA, opposite to low Runx-2 mRNA levels on SiO2-CaO-P2O5/PLGA films. All studied composites increased Osx mRNA levels. Whereas some of SiO2-CaO/PLGA composites did not elevate BMP-2 and -6 proteins in hBMSC cultures, high levels of these BMPs were present in all cultures on SiO2-CaO-P2O5/PLGA composites. All composites induced BMP-related Tak1 signalling, whereas Smad1 signalling was restricted mostly to composites containing three-component SBGs. ALP activity of hBMSC and BMP-related luciferase activity of mouse BRITE cells differed depending on whether the cells were stimulated with culture medium conditioned with SBG/PLGA composites or the cells were directly cultured on the composite surfaces. Altogether, beyond bioactivity and osteoinductivity of SBG/PLGA composites, our studies show key differences in the biological response to both the bioactive material dissolution products and upon direct cell-material contacts.

Mitochondria-targeted 1,4-naphthoquinone (SkQN) is a powerful prooxidant and cytotoxic agent.

An increase in the production of reactive oxygen species (ROS) in mitochondria due to targeted delivery of redox active compounds may be useful in studies of modulation of cell functions by mitochondrial ROS. Recently, the mitochondria-targeted derivative of menadione (MitoK3) was synthesized. However, MitoK3 did not induce mitochondrial ROS production and lipid peroxidation while exerting significant cytotoxic action. Here we synthesized 1,4-naphthoquinone conjugated with alkyltriphenylphosphonium (SkQN) as a prototype of mitochondria-targeted prooxidant, and its redox properties, interactions with isolated mitochondria, yeast cells and various human cell lines were investigated. According to electrochemical measurements, SkQN was more active redox agent and, due to the absence of methyl group in the naphthoquinone ring, more reactive as electrophile than MitoK3. SkQN (but not MitoK3) stimulated hydrogen peroxide production in isolated mitochondria. At low concentrations, SkQN stimulated state 4 respiration in mitochondria, decreased membrane potential, and blocked ATP synthesis, being more efficient uncoupler of oxidative phosphorylation than MitoK3. In yeast cells, SkQN decreased cell viability and induced oxidative stress and mitochondrial fragmentation. SkQN killed various tumor cells much more efficiently than MitoK3. Since many tumors are characterized by increased oxidative stress, the use of new mitochondria-targeted prooxidants may be a promising strategy for anticancer therapy.

Polarizing Graphene Quantum Dots toward Long-Acting Intracellular Reactive Oxygen Species Evaluation and Tumor Detection.

The evaluation of intracellular reactive oxygen species (ROS) would greatly deepen the understanding of cell metabolism/proliferation and tumor detection. However, current long-acting level tracking techniques for intracellular ROS remain unsuited to practical applications. To solve this problem, we synthesized cyclotriphosphazene-doped graphene quantum dots (C-GQDs) whose quantum yield is highly sensitive to ROS (increased by 400% from 0.12 to 0.63). Electron cloud polarization of oxidized cyclotriphosphazene rings in C-GQDs is confirmed to account for this novel optical property by density functional theory calculations and experimental results. In combination with excellent biological stability, C-GQDs achieve a long-acting evaluation of intracellular ROS level (more than 72 h) with an accuracy of 98.3%. In addition, recognition rates exceeding 90% are demonstrated to be feasible for eight kinds of tumor cell lines cultured with C-GQDs, which can also be expanded to in vivo detection. C-GQDs also show a high recognition rate (82.33%) and sensitivity (79.65%) for tumor cells in blood samples.

A Novel Approach for the Quantification of Different Inorganic and Organic Phosphorus Compounds in Environmental Samples by P L2,3-Edge X-ray Absorption Near-Edge Structure (XANES) Spectroscopy.

Phosphorus (P) is an essential element for life on Earth, with an important and oftentimes unaccounted organic biogeochemical component. Current methods for the quantification of different organic P compounds in environmental samples (e.g., soils, sediments) are based on extraction techniques and often associated with incomplete P recovery or sample changes. In this study, we present a protocol for the quantification of different organic and inorganic P species in soils using synchrotron-based X-ray absorption near-edge structure (XANES) spectroscopy at the P L2,3-edge. Its accuracy and precision was evaluated by analyzing 40 standard mixtures composed of seven different inorganic and organic P compounds (with a mean of R2 = 0.85). In addition, we quantified the P species of two soils and two agro-industrial byproducts using P L2,3-edge XANES spectroscopy and the results were compared with those obtained by P K-edge XANES or 31P NMR spectroscopy. Using the P L2,3-edge, we identified different organic P species, including those not identified by the common P K-edge XANES. However, there is a consistent underestimation of organic polyphosphates. Overall, the application of P L2,3-edge XANES provides a higher level of information than by P K-edge XANES, although the ubiquitous use of this novel methodology is still limited to samples with a phosphorus content above 3 mg g-1.

Preliminary studies of the effect of doping of chromium oxide in SiO2-CaO-P2O5 bioceramics for bone regeneration applications.

Bioceramics of composition xCr2O3∙(43-x) CaO∙42SiO2∙15P2O5 (x varying from 0 to 8 mol%) have been synthesized in the laboratory by using sol-gel technique. The morphology and structure has been determined by using Powder X-ray Diffraction, Fourier Transform Infrared and Raman spectroscopy and Field Emission Scanning Electron Microscopy. The in vitro bio mineralization behavior has been assessed by immersion in simulated body fluid for 7 days. The results obtained in our studies have indicated excellent hydroxyapatite formation ability of our samples. Drug delivery property of synthesized samples has been checked by using UV-spectroscopy of antibiotic 'gentamicin'. The in vitro drug release profile was fitted best in the Higuchi model with the highest value of coefficient of determination (R2 = 0.9970). Antimicrobial properties have been evaluated from minimum inhibitory concentration and time kill assay values. The cellular response has been investigated by using human osteosarcoma MG 63 cell line. Also to check charge on the synthesized samples, Zeta potential studies have been conducted and it has been observed that samples carry negative charge when immersed in simulated body fluid. Negative surface charge provide suitable environment for cell adhesion and proliferation. Experiments have been undertaken to explore suitable composition with an objective of development of suitable implant material for bone regeneration applications.

A luciferase lysis assay reveals in vivo malignant cell sensitization by phosphoantigen prodrugs.

Human Vγ9Vδ2 T cells respond to small phosphorus-containing compounds, often called phosphoantigens, which are now known to be intracellular ligands of the immune receptor butyrophilin 3A1 (BTN3A1). In order to compare the efficiency of butyrophilin ligands, we developed a luciferase-based lysis assay that measures the direct cytolysis by Vγ9Vδ2 T cells of luciferase-expressing K562 leukemia cells sensitized by phosphoantigen prodrugs. Our results show that the luciferase-based lysis assay allows in vitro and in vivo assessment of phosphoantigen activity in a way that does not require the extensive processing of flow cytometry or ELISA based approaches. In cellular assays, the structure activity relationships of phosphoantigen prodrugs correlate with ELISA-based activation assays, though phosphoantigen induced target cell lysis occurs at lower concentrations relative to T cell interferon γ production measured by ELISA. In mice dosed with phosphoantigens, a racemic aryl phosphonamidate prodrug, methyl 2-[[[(E)-5-hydroxy-4-methyl-pent-3-enyl]-(1-naphthyloxy)phosphoryl]amino]acetate (1-Nap/GlyOMe C-HMBP, 5), sensitized subcutaneous K562 tumors within minutes, and this effect was maintained at least four hours after treatment. In vivo activity of compound 5 was stronger than that of an equivalent dose of zoledronate. This luciferase lysis assay can be used for evaluation of phosphoantigens due to its time efficiency, high sensitivity, and in vivo compatibility and demonstrates rapid in vitro and in vivo sensitization of tumor cells by phosphoantigen prodrugs.

Bioinspired Thiophosphorodichloridate Reagents for Chemoselective Histidine Bioconjugation.

Site-selective bioconjugation to native protein residues is a powerful tool for protein functionalization, with cysteine and lysine side chains being the most common points for attachment owing to their high nucleophilicity. We now report a strategy for histidine modification using thiophosphorodichloridate reagents that mimic post-translational histidine phosphorylation, enabling fast and selective labeling of protein histidines under mild conditions where various payloads can be introduced via copper-assisted alkyne-azide cycloaddition (CuAAC) chemistry. We establish that these reagents are particularly effective at covalent modification of His-tags, which are common motifs to facilitate protein purification, as illustrated by selective attachment of polyarginine cargoes to enhance the uptake of proteins into living cells. This work provides a starting point for probing and enhancing protein function using histidine-directed chemistry.

One-step synthesis of novel phosphorus nitride dots for two-photon imaging in living cells.

Novel phosphorus nitride dots mainly consisting of N and P with strong fluorescence, excellent dispersibility and outstanding biocompatibility were prepared via a solvothermal method. The phosphorus nitride dots demonstrated great two-photon imaging capability in living cells under 800 nm excitation.

Methanolic extract of Tamarix Gallica attenuates hyperhomocysteinemia induced AD-like pathology and cognitive impairments in rats.

Although few drugs are available today for the management of Alzheimer's disease (AD) and many plants and their extracts are extensively employed in animals' studies and AD patients, yet no drug or plant extract is able to reverse AD symptoms adequately. In the present study, Tamarix gallica (TG), a naturally occurring plant known for its strong antioxidative, anti-inflammatory and anti-amyloidogenic properties, was evaluated on homocysteine (Hcy) induced AD-like pathology and cognitive impairments in rats. We found that TG attenuated Hcy-induced oxidative stress and memory deficits. TG also improved neurodegeneration and neuroinflammation by upregulating synaptic proteins such as PSD95 and synapsin 1 and downregulating inflammatory markers including CD68 and GFAP with concomitant decrease in proinflammatory mediators interlukin-1ß (IL1ß) and tumor necrosis factor α (TNFα). TG attenuated tau hyperphosphorylation at multiple AD-related sites through decreasing some kinases and increasing phosphatase activities. Moreover, TG rescued amyloid-ß (Aß) pathology through downregulating BACE1. Our data for the first time provide evidence that TG attenuates Hcy-induced AD-like pathological changes and cognitive impairments, making TG a promising candidate for the treatment of AD-associated pathological changes.

Cadmium alters heat shock protein pathways in SN56 cholinergic neurons, leading to Aß and phosphorylated Tau protein generation and cell death.

Cadmium, a neurotoxic environmental compound, produces cognitive disorders, although the mechanism remains unknown. Cadmium induces a more pronounced cell death on cholinergic neurons from basal forebrain (BF), mediated, in part, by increase in Aß and total and phosphorylated Tau protein levels, which may explain cadmium effects on learning and memory processes. Cadmium downregulates the expression of heat shock proteins (HSPs) HSP 90, HSP70 and HSP27, and of HSF1, the master regulator of the HSP pathway. HSPs proteins reduce the production of Aß and phosphorylated Tau proteins and avoid cell death pathways induction. Thus, we hypothesized that cadmium induced the production of Aß and Tau proteins by HSP pathway disruption through HSF1 expression alteration, leading to BF cholinergic neurons cell death. Our results show that cadmium downregulates HSF1, leading to HSP90, HSP70 and HSP27 gene expression downregulation in BF SN56 cholinergic neurons. In addition, cadmium induced Aß and total and phosphorylated Tau proteins generation, mediated partially by HSP90, HSP70 and HSP27 disruption, leading to cell death. These results provide new understanding of the mechanisms contributing to cadmium harmful effects on cholinergic neurons.

Osteomalacia, renal Fanconi syndrome, and bone tumor.

We herein report two cases of Fanconi syndrome with refractory hypophosphatemic osteomalacia that was difficult to correct by phosphorus replacement therapy. The pathological result was a bony giant cell tumor and osteosarcoma, respectively. Interestingly, after resection of the tumors, the patient with osteosarcoma recovered completely but the patient with the bony giant cell tumor had a relapse. Although she underwent nine operations, her symptoms and laboratory tests did not improve. These findings indicate that Fanconi syndrome can result from a bone tumor.

Spatially resolved chemical analysis of cicada wings using laser-ablation electrospray ionization (LAESI) imaging mass spectrometry (IMS).

Laser-ablation electrospray ionization (LAESI) imaging mass spectrometry (IMS) is an emerging bioanalytical tool for direct imaging and analysis of biological tissues. Performing ionization in an ambient environment, this technique requires little sample preparation and no additional matrix, and can be performed on natural, uneven surfaces. When combined with optical microscopy, the investigation of biological samples by LAESI allows for spatially resolved compositional analysis. We demonstrate here the applicability of LAESI-IMS for the chemical analysis of thin, desiccated biological samples, specifically Neotibicen pruinosus cicada wings. Positive-ion LAESI-IMS accurate ion-map data was acquired from several wing cells and superimposed onto optical images allowing for compositional comparisons across areas of the wing. Various putative chemical identifications were made indicating the presence of hydrocarbons, lipids/esters, amines/amides, and sulfonated/phosphorylated compounds. With the spatial resolution capability, surprising chemical distribution patterns were observed across the cicada wing, which may assist in correlating trends in surface properties with chemical distribution. Observed ions were either (1) equally dispersed across the wing, (2) more concentrated closer to the body of the insect (proximal end), or (3) more concentrated toward the tip of the wing (distal end). These findings demonstrate LAESI-IMS as a tool for the acquisition of spatially resolved chemical information from fragile, dried insect wings. This LAESI-IMS technique has important implications for the study of functional biomaterials, where understanding the correlation between chemical composition, physical structure, and biological function is critical. Graphical abstract Positive-ion laser-ablation electrospray ionization mass spectrometry coupled with optical imaging provides a powerful tool for the spatially resolved chemical analysis of cicada wings.

Phospholyl(borane) Amino Acids and Peptides: Stereoselective Synthesis and Fluorescent Properties with Large Stokes Shift.

The synthesis of phospholyl(borane) amino acids was stereoselectively achieved by reaction of phospholide anion with iodo α-amino ester derived from l-aspartic acid or l-serine, followed by in situ complexation with borane. Phospholyl(borane) amino acids are easy to store and can be subjected to direct transformation into the corresponding free phospholyl, gold complex, oxide or sulfur derivatives as well as phospholinium salts, thus offering a variety of side chains. After selective deprotection of carboxylic function or amine, C- or N- peptide coupling with an alanine moiety proved the possible incorporation into peptides. Such phospholyl amino acid and peptide derivatives exhibit fluorescent properties with a large Stokes shift (160 nm) and fluorescence up to 535 nm, depending on the phosphole aromaticity and the chemical environment. These phospholyl(borane) amino acids constitute a new class of unnatural amino acids useful for structure-activities relationship studies and appear to be promising fluorophores for the development of labeled peptides.

Eight Kinetically Stable but Thermodynamically Activated Molecules that Power Cell Metabolism.

Contemporary analyses of cell metabolism have called out three metabolites: ATP, NADH, and acetyl-CoA, as sentinel molecules whose accumulation represent much of the purpose of the catabolic arms of metabolism and then drive many anabolic pathways. Such analyses largely leave out how and why ATP, NADH, and acetyl-CoA (Figure 1 ) at the molecular level play such central roles. Yet, without those insights into why cells accumulate them and how the enabling properties of these key metabolites power much of cell metabolism, the underlying molecular logic remains mysterious. Four other metabolites, S-adenosylmethionine, carbamoyl phosphate, UDP-glucose, and Δ2-isopentenyl-PP play similar roles in using group transfer chemistry to drive otherwise unfavorable biosynthetic equilibria. This review provides the underlying chemical logic to remind how these seven key molecules function as mobile packets of cellular currencies for phosphoryl transfers (ATP), acyl transfers (acetyl-CoA, carbamoyl-P), methyl transfers (SAM), prenyl transfers (IPP), glucosyl transfers (UDP-glucose), and electron and ADP-ribosyl transfers (NAD(P)H/NAD(P)+) to drive metabolic transformations in and across most primary pathways. The eighth key metabolite is molecular oxygen (O2), thermodynamically activated for reduction by one electron path, leaving it kinetically stable to the vast majority of organic cellular metabolites.

Revealing the Cytotoxicity of Residues of Phosphazene Catalysts Used for the Synthesis of Poly(ethylene oxide).

We herein report a case study on the toxicity of residual catalyst in metal-free polymer. Eight-arm star-like poly(ethylene oxide)s were successfully synthesized via phosphazene-catalyzed ring-opening polymerization of ethylene oxide using sucrose as an octahydroxy initiator. The products were subjected to MTT assay using human cancer cell lines (MDA-MB-231 and A2780). Comparison between the crude and purified products clearly revealed that the residual phosphazenium salts were considerably cytotoxic, regardless of the anionic species, and that the cytotoxicity of more bulky t-BuP4 salt was higher than that of t-BuP2 salt. Such results have therefore put forward the necessity for removal of the catalyst residues from PEO-based polymers synthesized through phosphazene catalysis for biorelated applications and for the development of less or nontoxic organocatalysts for such polymers.