Phosphorus through the looking glass.

A key building block enables a general synthesis of chiral phosphorus drugs.

Synthesis of New Star-Shaped Liquid Crystalline Cyclotriphosphazene Derivatives with Fire Retardancy Bearing Amide-Azo and Azo-Azo Linking Units.

Two series of new hexasubstituted cyclotriphosphazene derivatives were successfully synthesized and characterized. These derivatives are differentiated by two types of linking units in the molecules such as amide-azo (6a-j) and azo-azo (8a-j). The homologues of the same series contain different terminal substituents such as heptyl, nonyl, decyl, dodecyl, tetradecyl, hydroxyl, carboxyl, chloro, nitro, and amino groups. All the intermediates and final compounds were characterized using Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR), and Carbon, Hydrogen, and Nitrogen (CHN) elemental analysis. Liquid crystal properties for all compounds were determined using polarized optical microscope (POM). It was found that only intermediates 2a-e with nitro and alkoxyl terminal chains showed a smectic A phase. All the final compounds with alkoxyl substituents are mesogenic with either smectic A or C phases. However, other intermediates and compounds were found to be non-mesogenic. The study on the fire retardancy of final compounds was determined using limiting oxygen index (LOI) method. The LOI value of pure polyester resin (22.53%) was increased up to 24.71% after treating with 1 wt% of hexachlorocyclotriphosphazene (HCCP). Moreover, all the compounds gave positive results on the LOI values and compound 6i with the nitro terminal substituent showed the highest LOI value of 27.54%.

Synthesis of OSL nanophosphor Li3B7O12:Mn and its dosimetric properties.

The present paper reports the structural, morphological and optical properties of nanophosphor Li3B7O12:Mn with an optimised dopant concentration of 0.25 mol% and its surface modification under the irradiation of 250 keV proton beams and gamma photons for ion fluence ranging from 1 × 1013 to 6.25 × 1015 ions cm-2 and doses from 100 mGy-100 Gy, respectively. This nanophosphor has been synthesised by the high temperature solid state reaction method. Its optical properties are characterised by optically stimulated luminescence (OSL) and thermo luminescence (TL) techniques. This nanophosphor is polycrystalline in nature with a grain size of 40-80 nm confirmed by x-ray diffraction (XRD) and transmission electron microscopy (TEM). The OSL decay and TL glow curve response of the proton beam irradiated samples exhibit significant intensity at a fluence of 2.5 × 1014 ions cm-2. Moreover, Li3B7O12:Mn displays a linear response for gamma doses in the range of 100 mGy-50 Gy. We have also investigated the reusability and reproducibility of this material. The above study demonstrates that Li3B7O12:Mn is a robust and promising candidate for medical proton dosimetry.

Feasibility of applying the LED-UV-induced TiO2/ZnO-supported H3PMo12O40 nanoparticles in photocatalytic degradation of aniline.

In the present study, TiO2/ZnO-supported phosphomolybdic acid nanoparticles are investigated by the impregnation method, followed by analyzing their photocatalytic activity under UV-LED light and degradation kinetics degrading aniline as an organic pollutant model. Nanoparticle characteristics and the remaining Keggin structure in the nanocomposites were confirmed by means of FESEM, FTIR, and XRD analyses. Heterogenization of phosphomolybdic acid on TiO2 and ZnO nanoparticles resulted in the improved light absorption intensity and decreased band gap of nanocomposites. Photocatalytic degradation of aniline was also improved for composite nanoparticles and reached to 25.62, 43.48, and 38.25% for TiO2/HPMo, ZnO/HPMo, and TiO2/ZnO/HPMo, respectively. Overall, the results showed a good fit to the Langmuir-Hinshelwood kinetic model.

Phosphorylation, oligomerization and self-assembly in water under potential prebiotic conditions.

Prebiotic phosphorylation of (pre)biological substrates under aqueous conditions is a critical step in the origins of life. Previous investigations have had limited success and/or require unique environments that are incompatible with subsequent generation of the corresponding oligomers or higher-order structures. Here, we demonstrate that diamidophosphate (DAP)-a plausible prebiotic agent produced from trimetaphosphate-efficiently (amido)phosphorylates a wide variety of (pre)biological building blocks (nucleosides/tides, amino acids and lipid precursors) under aqueous (solution/paste) conditions, without the need for a condensing agent. Significantly, higher-order structures (oligonucleotides, peptides and liposomes) are formed under the same phosphorylation reaction conditions. This plausible prebiotic phosphorylation process under similar reaction conditions could enable the systems chemistry of the three classes of (pre)biologically relevant molecules and their oligomers, in a single-pot aqueous environment.

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.

Super-Photostable Phosphole-Based Dye for Multiple-Acquisition Stimulated Emission Depletion Imaging.

As stimulated emission depletion (STED) microscopy can provide structural details of cells with an optical resolution beyond the diffraction limit, it has become an indispensable tool in cell biology. However, the intense STED laser beam usually causes rapid photobleaching of the employed fluorescent dyes, which significantly limits the utility of STED microscopy from a practical perspective. Herein we report a new design of super-photostable dye, PhoxBright 430 (PB430), comprising a fully ring-fused π-conjugated skeleton with an electron-accepting phosphole P-oxide unit. We previously developed a super-photostable dye C-Naphox by combining the phosphole unit with an electron-donating triphenylamine moiety. In PB430, removal of the amino group alters the transition type from intramolecular charge transfer character to π-π* transition character, which gives rise to intense fluorescence insensitive to molecular environment in terms of fluorescence colors and intensity, and bright fluorescence even in aqueous media. PB430 also furnishes high solubility in water, and is capable of labeling proteins with maintaining high fluorescence quantum yields. This dye exhibits outstanding resistance to photoirradiation even under the STED conditions and allows continuous acquisition of STED images. Indeed, using a PB430-conjugated antibody, we succeed in attaining a 3-D reconstruction of super-resolution STED images as well as photostability-based multicolor STED imaging of fluorescently labeled cytoskeletal structures.

Novel heteroaryl phosphonicdiamides PTPs inhibitors as anti-hyperglycemic agents.

BACKGROUND: Chronic and oral administration of benzylamine improves glucose tolerance. Picolylamine is a selective functional antagonist of the human adenosine A2B receptor. Phosphonic diamide derivatives enhance the cellular permeability and in turn their biological activities. METHODS: A series of heteroaryl phosphonicdiamide derivatives were designed as therapeutics to control and manage type2 diabetes. Initially defined Lipinski parameters encouraged them as safer drugs. Molecular docking of these compounds against Protein tyrosine phosphatase (PTP), the potential therapeutic target of type 2 diabetes, revealed their potential binding ability explaining their anti-diabetic activity in terms of PTP inhibition. Human intestinal absorption, Caco-2 cell permeability, MDCK cell permeability, BBB penetration, skin permeability and plasma protein binding abilities of the title compounds were calculated by PreADMET server. A convenient method has been developed for the synthesis of title compounds through the formation of 1-ethoxy-N,N'-bis(4-fluorobenzyl/pyridin-3-ylmethyl)phosphinediamine by the reaction of 4-fluorobenzylamine/ 3-picolylamine with ethyldichlorophosphite, subsequently reacted with heteroaryl halides using lanthanum(III) chloride as a catalyst. RESULTS: All the compounds exhibited significant in vitro anti-oxidant activity and in vivo evaluation in streptozotocin induced diabetic rat models revealed that the normal glycemic levels were observed on 12(th) day by 9a and 20(th) day by 5b, 5c, 9e and 9f. The remaining compounds also exhibited normal glycemic levels by 25(th) day. CONCLUSION: The results from molecular modeling, in vitro and in vivo studies are suggesting them as safer and effective therapeutic agents against type2 diabetes. Graphical Abstract Development of PTPs inhibitors.

Phosphorus-nitrogen compounds. Part 29. Syntheses, crystal structures, spectroscopic and stereogenic properties, electrochemical investigations, antituberculosis, antimicrobial and cytotoxic activities and DNA interactions of ansa-spiro-ansa cyclotetraphosphazenes.

A number of novel ansa-spiro-ansa (asa) cyclotetraphosphazenes (1a-5b) was prepared in the range of 63-90 % yields. The structures of the compounds were verified by MS, FTIR, (1)H, (13)C{(1)H} and (31)P{(1)H} NMR, heteronuclear single quantum coherence (HSQC), and heteronuclear multiple-bond correlation (HMBC) techniques. The crystal structures of 1b, 2c and 5a were determined by X-ray crystallography. The compound 2c was analyzed by the changes in the (31)P{(1)H}NMR spectrum in addition of the chiral solvating agent; (R)-(+)-2,2,2-trifluoro-1-(9'-anthryl)-ethanol (CSA), to investigate its stereogenic properties. The result supports that compound 2c was found to be in the racemic mixture. Cyclic voltammetric and chronoamperometric data of the mono-ferrocenyl-spiro-asa-cyclotetraphosphazenes exhibited electrochemically reversible one-electron oxidation of Fe redox centres. The mono-ferrocenyl-spiro-asa compounds (3a-5b) were evaluated for antituberculosis activity against reference strain Mycobacterium tuberculosis H37Rv and M. tuberculosis clinical strain, which is resistant to rifampicin and isoniazid. These compounds appear not to be good candidates for being antituberculosis agents to clinical strains. All of the compounds were screened for antibacterial activities against G(+) and G(-) bacteria, and for antifungal activities against yeast strains. They seem to be more active against Gram positive bacteria than Gram negative. The interactions of the phosphazenes with plasmid DNA and the evaluations for cytotoxic activity against MCF-7 breast cancer cell lines were investigated. The compounds 1b, 2b, 3a and 4a were found to be more effective than Cisplatin against MCF-7 breast cancer cell lines at lower concentrations.

Phosphaannulation by palladium-catalyzed carbonylation of C-H bonds of phosphonic and phosphinic acids.

An efficient phosphaannulation by Pd-catalyzed carbonylation of C-H bonds of phosphonic and phosphinic acids for the synthesis of oxaphosphorinanone oxides is reported. These compounds are novel phosphorus heterocyclic scaffolds, thus opening a new avenue to sequential C-C/C-O bond formation in one pot.

Synthesis of pyridyl-dihydrobenzooxaphosphole ligands and their application in asymmetric hydrogenation of unfunctionalized alkenes.

Synthesis of the electron-rich 2-substituted-6-(phenylsulfonyl)pyridines is presented. A series of air-stable, tunable, P-chiral pyridyl-dihydrobenzooxaphosphole ligands were designed and synthesized by a diastereoselective S(N)Ar substitution of the corresponding sulfonyl pyridines. The ligands were successfully applied in the Ir-catalyzed asymmetric hydrogenation of unfunctionalized alkenes with good enantioselectivities.

Mapping the pathway toward thiophosphinic pseudopeptides. Synthesis of suitably protected PG-Phe-Ψ[P(S)(OX)CH2]-Gly-OY analogues as thiophosphinyl dipeptide isosters (TDI), a comparative study for selective deprotection and further elongation.

In the present study, we describe in detail the first synthesis of a new class of phosphorus compounds, thiophosphinyl pseudopeptides. We prepared several fully protected thiophosphinate pseudodipeptides of the general formula PG-Phe-Ψ[P(S)(OX)CH2]-Gly-OY starting from the corresponding phosphinate pseudodipeptide using Lawesson's reagent. Selective deprotection, further elongation, and stability of these compounds were studied, and the results are disclosed. These compounds can be used as transition-state-mimicking inhibitors for several zinc metalloproteases.

Synthesis, cytotoxicity and apoptosis of cyclotriphosphazene compounds as anti-cancer agents.

In the present study, a number of new dispirobino and dispiroansa spermine derivatives of cyclotriphosphazene (8-10, 13) were synthesized and characterized by elemental analysis, mass spectrometry, (1)H and (31)P NMR spectroscopy. At first, in vitro cytotoxic activity of cyclotriphosphazene compounds (1-14) against HT-29 (human colon adenocarcinoma), Hep2 (Human epidermoid larynx carcinoma), and Vero (African green monkey kidney) cell lines was investigated. Our study showed that most of these compounds stimulate apoptosis and they have cytotoxic effects for HT-29 and Hep2 cells. Additionally, these compounds (1-14) were investigated for their antibacterial activity against gram-positive (Staphylococcus aureus), gram-negative (Escherichia coli, Pseudomonas aeruginosa) bacteria and for their antifungal activity against Candida albicans, and were shown to be inactive.

P=C-N-heterocycles: synthesis of biaryl-type 1,3-benzazaphospholes with ortho-substituted phenyl or 2-heteroaryl groups.

A facile synthesis of functionally substituted 2-(hetero)aryl 1,3-benzazaphospholes via nickel- or palladium-catalyzed phosphonylation of N-acyl-2-bromoanilides 1a-k with triethyl phosphite is presented. Anilidophosphonates 2a-g with naphthoyl-, o-substituted phenyl, furoyl- or thenoyl groups allow direct reductive cyclization with LiAlH(4) to benzazaphospholes 3. The reaction of the o-bromoderivative 2d proceeds with concomitant replacement of bromine by hydrogen, whereas the electron-withdrawing pyridyl group of 2h prevents the synthesis of 3h by this short route. An alternative synthesis of 2-pyridylbenzazaphosphole 3hvia anilidophosphonates succeeded starting from Fmoc-anilinophosphonate 2kvia selective cleavage of the N-protecting group, reduction of the resulting phosphonoaniline to phosphinoaniline and cyclization with pyridine-2-carboxaldehyde via a dihydrobenzazaphosphole 8. N-Substituted pyridylmethylbenzazaphosphole 9 was detected as a side product. The structure elucidation of the new compounds is based on multinuclear NMR data and X-ray crystal structure analyses of a phosphonoanilide, underlining the dominance of N-H···O=P hydrogen bonds over N-H···O=C type hydrogen bonds, of 3h and a supramolecular associate of 3b and its unprecedented air oxidation product 10.

Synthesis, characterization, oxidative degradation, antibacterial activity and acetylcholinesterase/butyrylcholinesterase inhibitory effects of some new phosphorus(V) hydrazides.

Some new phosphorus(V) hydrazides 1a-12a were synthesized and characterized by (1)H, (13)C, (31)P NMR, IR spectroscopy and elemental analysis. Moreover, the interaction of Cu(M)(2)·nH(2)O with 1a, 3a and 7a gave 4,4'-bis(morpholine)diazene (1b). In fact, in these reactions, copper(II) ions acted as oxidizing agent. The results supported the proposed mechanism. The structures of compounds 1a, 1b and 1c were further determined by X-ray crystallography. Compounds 1a-12a were screened for their antibacterial activities. Also, the acetyl- and butyrylcholinesterase inhibitory activity of 1a, 3a, 7a, 11a and 12a was measured using Ellman's method. It is interesting that these compounds were more potent inhibitors of BChE than of AChE. Also, using Lineweaver-Burk plots, it was indicated these compounds are mixed inhibitors.

Synthesis and characterization of novel organotin-phosphorous compounds II.

New organotin substituted alpha-anilinomethylphosphonates were prepared and were characterized by FT-IR, 1H- and 13C-NMR spectroscopy and elemental microanalysis.

Determination of the absolute configuration of pentacoordinate chiral phosphorus compounds in solution by using vibrational circular dichroism spectroscopy and density functional theory.

Vibrational circular dichroism (VCD) spectroscopic measurements and density functional theory (DFT) calculations have been used to obtain the absolute structural information about four sets of diastereomers of pentacoordinate spirophosphoranes derived separately from l- (or d-) valine and l- (or d-) leucine for the first time. Each compound contains three stereogenic centers: one at the phosphorus center and two at the amino acid ligands. Extensive conformational searches for the compounds have been carried out and their vibrational absorption (VA) and VCD spectra have been simulated at the B3LYP/6-311++G** level. Although both VA and VCD spectra are highly sensitive to the structural variation of the apical axis, that is, the O-P-O or N-P-O arrangement, the rotamers generated by the aliphatic amino side chains show little effect on both. The dominant experimental VCD features in the 1100-1500 cm(-1) region were found to be controlled by the chirality at the phosphorus center, whereas those at the C=O stretching region are determined by the chirality of the amino acid ligands. The good agreement between the experimental VA and VCD spectra in CDCl(3) solution and the simulated ones allows us to assign the absolute configurations of these pentacoordinate phosphorus compounds with high confidence. This study shows that the VCD spectroscopy complemented with DFT calculations is a powerful and reliable method for determining the absolute configurations and dominating conformers of synthetic phosphorus coordination complexes in solution.

Synthesis and antibacterial activity of some new thiadiaza/triazaphospholes, thiadiaza/triaza/tetrazaphosphinines and thiadiaza/tetrazaphosphepines containing 1,2,4-triazinone moiety.

Some new thiadiaza/triazaphospholes, thiadiaza/triaza/tetrazaphosphinines and thiadiaza/tetrazaphosphepines fused with 6-methyl-1,2,4-triazin-5-one moiety were synthesized via reactions of alpha,beta-bifunctional compounds derived from 4-amino-3-mercapto-6-methyl-1,2,4-triazin-5(4H)-one (1) with various phosphorus reagents. The in vitro antibacterial activities of the synthesized compounds were evaluated against some bacterial strains. Compounds 16 and 21 exhibited good inhibitory activities against most the tested organisms with MIC values in the range 6.25-12.5 microg/mL and lower cytotoxicity in comparison with the reference drugs.