Aminophosphonates Research Articles

Organo‐Soluble Colloidal MoS2 Quantum Dots (QDs) as an Efficient Photocatalyst for α‐Amino Phosphonate Synthesis

Abstractα‐Amino phosphonates are bio‐isosteres of amino acids and have numerous biochemical activities. While they are generally prepared via carbon–phosphorus bond formation using a plethora of methods but using recyclable photo‐catalysts and readily accessible amine and phosphites are not commonly used in synthesis. Herein, we used organo‐soluble MoS2 Quantum Dots (QDs) as an exceptionally efficient nano‐photocatalyst for the synthesis of α‐amino phosphonates. Our approach emphasizes on photocatalysis within organic media, providing a facile and effective method for conducting these intricate organic conversions under mild conditions. This straightforward process harnesses the power of molecular oxygen (O2) as an oxidizing agent. To elaborate, our method is intricately guided by the inherent capability of MoS2 QDs to enter an excited state upon absorption of blue light. This excited state bears appropriate potential energy to initiate the formation of reactive iminium ion species from N‐phenyl benzylamine, thus driving the desired product formation. Mechanistic analysis has also unveiled the pivotal role of MoS2 QDs in generating reactive superoxide radicals from O2 through single electron transfer (SET), underscoring their significance in the process. Remarkably, this photocatalytic transformation furnishes a diverse array of functionalized products, expanding its applicability and potential implications in various contexts.

Synthesis of new amino phosphonates based on secondary amines using microwave activation and phthalocyanine catalysis

Synthesis of new amino phosphonates based on secondary amines using microwave activation and phthalocyanine catalysis

Antimicrobial agents based on new lipophilic alkyl (N-alkyl-N,N-dioctylammoniomethyl)phosphonates

(N-Alkyl-N,N-dioctylammoniomethyl)phosphonates were obtained by alkylation of amino phosphonate potassium salt with alkyl iodides or benzyl chloride. All synthesized compounds demonstrated high antibacterial and antifungal activity against Gram-positive bacterial strains B. cereus and S. aureus and were not active against Gram-negative strains Ps. aeruginosa. Some regularity connecting the structure of the obtained compounds with their antimicrobial action has been established.

Performance and Reaction Mechanism of Co(Ⅱ) Mediated Activation of Peroxymonosulfate for Degrading Nitrilotris (Methylene Phosphonic Acid)

Co(Ⅱ) mediated activation of peroxymonosulfate (PMS) could degrade phosphonate effectively, whereas the degradation of amino phosphonate remains unclear. Herein, nitrilotris (methylene phosphonic acid) (NTMP) was used as a target pollutant; the degradation mechanism was investigated using the electron paramagnetic resonance spectrum (EPR), free radical trapping experiments, and chemical probe experiments; and the possible degradation pathways of NTMP and the influencing factors were analyzed. The results showed that NTMP was completely degraded within 20 min in the Co(Ⅱ)/PMS system, and 78.3% of NTMP was oxidized to orthophosphate (PO43-) after 60 min of reaction. The Co(Ⅱ)-PMS complex was the main active oxidizing species, whereas 1O2, HO·, and SO4-· contributed little to the oxidation of NTMP in the Co(Ⅱ)/PMS system. A variety of intermediates containing phosphate groups were obtained through the breakage of the C-N bond and C-P bond as NTMP reacted with the Co(Ⅱ)-PMS complex and finally were oxidized to PO43-. With the increase in PMS dosage and Co(Ⅱ) dosage, the generation rate of PO43- during the oxidation process of NTMP was significantly improved. In addition, the presence of HCO3- and natural organic matter (NOM) greatly inhibited the generation of PO43- in the Co(Ⅱ)/PMS system. This study further improved the oxidation mechanism of phosphonate in the Co(Ⅱ)/PMS system and provides a reference for the removal of phosphonate in wastewater.

O-21 - Towards sustainable production of gallium-68: recovery of gallium-68 and zinc from HNO3-based cyclotron liquid target by liquid-liquid extraction with amino phosphonates

O-21 - Towards sustainable production of gallium-68: recovery of gallium-68 and zinc from HNO3-based cyclotron liquid target by liquid-liquid extraction with amino phosphonates

Flame retardation of polyester/cotton blended fabrics via intumescent sol-gel coatings

Sol-gel coatings have long been applied to improve the flame retardancy of fabrics, but they often exhibit unsatisfactory flame-retardant efficiency for polyester/cotton blended fabrics. Therefore, an intumescent coating called DAM was constructed in this work by modifying 3-aminopropyl triethoxysilane with amino phosphonates and melamine through neutralizition reaction of the ingredients. Then, DAM was deposited on the surface of the fabric as a homogeneous coating via sol-gel technique. It was found that DAM accelerated the dehydration of cotton at a relatively low temperature but did not influence the thermal decomposition of polyester. With DAM add-ons of 8% and 15%, the coated fabrics severally named DAM-8 and DAM-15, self-extinguished in horizontal and vertical flame tests, with liming oxygen index values of 23.0% and 26.0%, respectively. In the cone calorimetry test, the ignition of the fabric was slightly delayed owing to the presence of the DAM, while the total heat release and peak heat release rate of the DAM-15 were reduced by 26.1% and 46.3%, respectively. DAM showed flame-retardant activities in both condensed and gaseous phases. Hand assessment of the fabric via the PhabrOmeter system suggested that the presence of the DAM caused the coated fabric to be smoother but a little more rigid than the uncoated fabric.

Facile Conversion of α-Amino Acids into α-Amino Phosphonates by Decarboxylative Phosphorylation using Visible-Light Photocatalysis.

Amino phosphonates exhibit potent inhibitory activity for a wide range of biological processes due to their specific structural and electronic properties, making them important in a plethora of applications, including as enzyme inhibitors, herbicides, antiviral, antibacterial, and antifungal agents. While the traditional synthesis of α‐amino phosphonates has relied on the multicomponent Kabachnik‐Fields reaction, we herein describe a novel and facile conversion of activated derivatives of α‐amino acids directly to their respective α‐amino phosphonate counterparts via a decarboxylative radical–polar crossover process enabled by the use of visible‐light organophotocatalysis. The novel method shows broad applicability across a range of natural and synthetic amino acids, operates under mild conditions, and has been demonstrated to successfully achieve the late‐stage functionalization of drug molecules.

A convenient synthesis, biological activity and X-ray crystallography of novel α-aminophosphonate derivatives

A new series of novel α-aminophosphonate derivatives have been synthesized by new rapid and convenient approach, based on the stepwise one pot reaction of 2-hydroxyaniline, aromatic aldehydes and triethyl phosphite. The structures of all compounds have been identified by appropriate spectroscopic methods such as FTIR, 1H, 13C, 31P NMR and ESI-MS. The crystal structure of diethyl-(2-fluorophenyl)-(2-hydroxy-4-methylphenyl)amino phosphonate has been determined, it crystallizes in the P-1 space group. In vitro antifungal activity of the synthesized compounds were tested against wheat fusarium (Fusarium oxysporum) and compared with standard antifungal drug Chlorpyriphos EC to explore their potential antifungal activity. We also measured the antioxidant activity of these molecules, compared with vitamin C as standard antioxidant.

Biological activity of new amino phospha betaines with C10–C18 alkyl groups

New amino phospha betaines were obtained by quaternization of potassium salt of amino phosphonate and higher alkyl bromides. The structure of isopropyl (N-dodecyl-N,N- dimethylammoniomethyl)phosphonate was confirmed by single crystal X-ray diffraction. All synthesized compounds demonstrate high antibacterial and antifungal activities.

Stereochemistry of the Kabachnik‐Fields Condensation of Terpenic Amino Oximes with Aldehydes and Dimethyl Phosphite

AbstractThree‐component condensation of aldehydes and dimethyl phosphite with α‐amino oximes derived from (−)‐α‐pinene and (+)‐3‐carene (Kabachnik‐Fields reaction) resulted in amino phosphonates as pairs of diastereomers. Diastereomeric ratio depends on the catalyst used (SnCl2×2H2O, SiO2, Al2O3‐H+) and the heating type (conventional or microwave). The best results were achieved by MW irradiation with simultaneous cooling. Stereochemical assignment of the key derivatives was made by X‐ray diffractometry. According to quantum chemical calculations (DFT PBE0/def2‐TZVPP) and spectroscopic data, the terpenic α‐amino phosphonates should be conformationally inhomogeneous, exhibiting a tendency to form H‐bonded dimers (DFT M06/def2‐SVP, IR). One‐bond spin‐spin coupling 1JP–C was found to be diagnostic for the configuration assignment since the value 1JP–C depends on the dihedral angle between bond C−P and axis of the electron lone pair at the neighboring nitrogen (NMR, DFT PBE0/aug‐cc‐pVTZ−J).

Synthesis, Physical Chemistry, Molecular Docking, Bioactivities and Antioxidant Activity of α–Amino Phosphonates Based on Phenothiazine Using PEG–400 as Green Catalyst

AbstractThe analog α–amino phosphates (5 a–j) based on phenothiazine were synthesized, characterized and tested for their anti‐microbial and antioxidant activities. Among the target compounds, (5 a–j), the compounds (5 c) and (5 i) indicated the potential activity against Staphylococcus aureus bacterium at the concentration of 100 μM. Compound (5e) showed good activity against the 100 μM Candida albicans fungi while compound (5 g) showed excellent activity against 25 μM Saccharomyces cerevisiae fungi. In addition, molecular docking study was used to establish the interactive binding behavior of (5 g) within the active site of the target protein (PDB:3 A4 A). Among the tested compounds (5 a–j), the compound (5 f) indicated the highest antioxidant activity, IC50 2.19 μM, antioxidant activity greater than that of ascorbic acid and lower than that of the drug BHT. In particular, PEG–400 (Polythylene glycol 400 g mol−1) was used in the Kabachnik‐Fields reaction as a green reaction medium.

Comparative screening of tetra-chlorometallate anions in novel magnetic metallogeminisurfactant catalysts for advanced synthesis of an anti-tumor benzothiazol-based aminophosphonate drug (ACBTAP)

Due to the high surface activity and low critical micelle concentration (CMC) of metallogemini-surfactants (MGSs), in this work various magnetic MGSs (MMGS1s) were prepared by simple grinding of low-cost hydrated salts of Fe3+, Co2+, Mn2+ and Ni2+ with GS1 synthesized by an improved solvent-free method. These new MMGS1s, which are complexes of 2FeCl4−, CoCl42−, MnCl42−, and NiCl42− with GS1, were characterized by UV–Vis, FT-IR, and melting point (mp) analyses. So, the maximum UV–Vis absorption wavelength was due to the GS12+·CoCl42− and the minimum mp and pH were due to the GS12+ ·2FeCl4− (MFeGS1). The results of the catalytic activities of MMGS1s in solvent-free synthesis of anticancer O,O′-diethyl-α-(benzothiazole-2-yl)amino(phenylmethyl) phosphonate (ACBTAP) revealed the superiority of MFeGS1, although catalysts were isolated as aqueous magnetic liquids (MLs) by addition of water. The aqueous MLs were further prepared in 0.01 and 0.1 molar concentration and analyzed by pH, surface tension (ᵞ), superconducting quantum interface device magnetometer (SQUID), and magnetic tests. Similar to GS1, all MMGS1s reduced the ᵞ of water by a half time ratio, while the magnetic activity of their aqueous MLs confirmed by magnetic drop-deviation and drop-movement over organic phase. The SQUID analysis of the aqueous MLs supported ferromagnetic properties for solution of MCoGS1, MNiGS1, and MMnGS1 in water and paramagnetic properties for the aqueous solution of GS12+·2FeCl4−. The as-prepared MLs are novel polar alternatives for organic solvents, water-treatment sorbents, and magnetic delivery of biomaterials.

Carbene-Catalyzed [4 + 2] Cycloadditions of Vinyl Enolate and (in Situ Generated) Imines for Enantioselective Synthesis of Quaternary α-Amino Phosphonates.

A carbene-catalyzed enantioselective addition of enals to five-membered cyclic imines is developed. The reaction gives chiral quaternary α-amino phosphonates bearing tetrasubstituted carbon centers with excellent enantioselectivities. The imine substrates can be generated in situ from the corresponding amines under an oxidative condition that is compatible with the carbene catalysis. Thus, a one-pot cross-dehydrogenative-coupling (CDC) reaction between enals and amines is also realized with high enantioselectivity remaining. The method provides quick enantioselective access to amino phosphonates with potential applications in medicines and pesticides.

$${\hbox {SO}}_{3}\hbox {H}$$ SO 3 H -functionalized magnetic $${\hbox {Fe}}_{3} {\hbox {O}}_{4}$$ Fe 3 O 4 nanoparticles as an efficient and reusable catalyst for one-pot synthesis of $${\upalpha }$$ α -amino phosphonates

Nanomagnetic $$\hbox {Fe}_{{3}} \hbox {O}_{{4}} @ \hbox {SiO}_{{2}}\hbox {-SO}_{{3}}\hbox {H}$$ ( $$\hbox {SO}_{{3}}\hbox {H-MNPs}$$ ) was prepared via grafting sulfonic acid on the silica-coated $$\hbox {Fe}_{{3}} \hbox {O}_{{4}}$$ magnetite nanoparticles (MNPs). The catalytic activity of the prepared $$\hbox {SO}_{{3}}\hbox {H-MNPs}$$ was probed through the one-pot synthesis of N-hydroxy- $${\upalpha }$$ -amino phosphonates and $${\upalpha }$$ -amino phosphonates via three-component couplings of phenylhydroxylamine or amines with aldehydes and trialkyl phosphites at room temperature. The synthesized $$\hbox {SO}_{{3}}\hbox {H-MNPs}$$ were characterized by XRD, FT-IR, and SEM. The recoverability of the catalyst was achieved by a simple magnetic decantation and reused at least five times without significant degradation in catalytic activity. The catalytic activity of the prepared $$\hbox {SO}_{{3}}\hbox {H-MNPs}$$ was probed through the one-pot synthesis of N-hydroxy- $${\upalpha }$$ -amino phosphonates and $${\upalpha }$$ -amino phosphonates via three-component couplings of phenylhydroxylamine or amines with aldehydes and trialkyl phosphites at room temperature.

The synthesis and kinetic evaluation of aryl α-aminophosphonates as novel inhibitors of T. cruzi trans-sialidase

The trans-sialidase protein expressed by Trypanosoma cruzi is an important enzyme in the life cycle of this human pathogenic parasite and is considered a promising target for the development of new drug treatments against Chagas' disease. Here we describe α-amino phosphonates as a novel class of inhibitor of T. cruzi trans-sialidase. Molecular modelling studies were initially used to predict the active-site binding affinities for a series of amino phosphonates, which were subsequently synthesised and their IC50s determined in vitro. The measured inhibitory activities show some correlation with the predictions from molecular modelling, with 1-napthyl derivatives found to be the most potent inhibitors having IC50s in the low micromolar range. Interestingly, kinetic analysis of the mode of inhibition demonstrated that the α-aminophosphonates tested here operate in a non-competitive manner.

Effect of different immobilization strategies on chiral recognition properties of Cinchona-based anion exchangers.

In the enantiomeric separation of highly polar compounds, a traditionally challenging task for high-performance liquid chromatography, ion-exchange chiral stationary phases have found the main field of application. In this contribution, we present a series of novel anion-exchange-type chiral stationary phases for enantiomer separation of protected amino phosphonates and N-protected amino acids. Two of the prepared selectors possessed a double and triple bond within a single molecule. Thus, they were immobilized onto silica support employing either a thiol-ene (radical) or an azide-yne (copper(I)-catalyzed) click reaction. We evaluated the selectivity and the effect of immobilization proceeding either by the double bond of the Cinchona alkaloid or a triple bond of the carbamoyl moiety on the chromatographic performance of the chiral stationary phases using analytes with protecting groups of different size, flexibility, and π-acidity. The previously observed preference toward protecting groups possessing π-acidic units, which is a typical feature of Cinchona-based chiral stationary phases, was preserved. In addition, increasing the bulkiness of the selectors' carbamoyl units leads to significantly reduced retention times, while very high selectivity toward the tested analytes is retained.

Analysis and application of the SRBSDV P9-1 octamer crystal structure for the target of α-amino phosphonate derivatives

// Yan Ding 1 , Xiangyang Li 1 , Kai Chen 1 , Guoping Zhang 1 , Liangzhi Luo 1 , Deyu Hu 1 and Baoan Song 1 1 State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Huaxi District, Guiyang 550025, PR China Correspondence to: Baoan Song, email: basong@gzu.edu.cn Xiangyang Li, email: xyli1@gzu.edu.cn Keywords: targets; SRBSDV P9-1; octamers; bind to; α-amino phosphonate derivatives Received: October 17, 2017      Accepted: December 05, 2017      Published: January 13, 2018 ABSTRACT Southern rice black-streaked dwarf virus (SRBSDV) P9-1 octameric protein accumulates viroplasms in SRBSDV-infected plant and insect cells, our previous studies found α-amino phosphonate drug—dufulin had a micromole affinity with SRBSDV P9-1. Now we focus our studies on the SRBSDV P9-1 crystal structure and use it as the target for α-amino phosphonate derivatives. The structure of the SRBSDV P9-1 cylindrical octamer was determined to a 2.2 Å resolution using X-ray crystallography, this structure was composed of nine α-helices, nine β -sheets and a series of interconnecting loops. The structures of all eight subunits were nearly identical, except for some differences in the β -sheet core. There were six different sites (R20K, V109D, F164T, V123L, C124L and V128T) present between the SRBSDV P9-1 and the previously reported RBSDV P9-1 crystal structure. Fluorescence titration, isothermal calorimetry and microscale thermophoresis experiments showed that α-amino phosphonate derivatives GUFCC-013 and GUFCC-023 bound to SRBSDV P9-1 with micromole binding affinities. These results will provide important help for the further improvement of the lead compound and develop the potential anti-SRBSDV drugs.

Synthesis and Characterization of Novel Azo Disperse Dyes Containing -amino Phosphonate and Their Dyeing Performance on Polyester Fabric

Three novel azo disperses dyes were designed, synthesized, and characterized by utilizing of α-aminophosphonates chromophors. The target compounds were prepared by employing of benzidine as amine and different heterocyclic formyl as aldehyde, and triphenylphosphite P(OC6H5)3 that gives -aminophosphonate in one position and free amino group in the other position, which was then coupled with β–naphthol to give the target products azo disperse dyes. The structures of all the synthesized dyes were established by IR, 1HNMR and mass spectral data and applied to polyester fabric as azo disperse dyes and all fastness properties for the dyed samples were measured.

Structure based design, synthesis and biological evaluation of amino phosphonate derivatives as human glucokinase activators

Glucokinase (GK) is a potential therapeutic target of type 2 diabetes and GK activators (GKAs) represent a promising class of small organic molecules which enhance GK activity. Based on the configuration and conformation of the allosteric site of GK, we have designed a novel class of amino phosphonate derivatives in order to develop potent GKAs. The QSAR model developed using numerous descriptors revealed its potential with the best effective statistical values of RMSE=1.52 and r2=0.30. Moreover, application of this model on the present test set GKAs proved to be worthy to predict their activities as a better linear relationship was observed with RMSE=0.14 and r2=0.88. ADME studies and Lipinski filters encouraged them as safer therapeutics. The molecular dynamics and docking studies against the GK allosteric site revealed that all GKAs bind with best affinities and the complexes are strengthened by H-bonding, phosphonate salt bridges, hydrophobic and arene cat ionic interactions. Finally, in vitro evaluation with human liver GK revealed their potential to increase the GK activity by different folds. The results from QSAR, ADME, molecular docking and in vitro assays strongly suggested that the present molecules could be used as effective and safer therapeutics to control and manage type 2 diabetes.

Comparative study of the application of chelating resins for rare earth recovery

The adsorption properties of chelating ion exchange resins containing mixed sulfonic/phosphonic (SP), aminophosphonic (AP) or iminodiacetic (IDA) acid functional groups were investigated towards the rare earth elements (REE). The aim of this work was to determine the potential for such resins to assist in the isolation of a mixed rare earth product under conditions relevant to the hydrometallurgical processing of rare earth containing minerals. The selectivity of the resins towards La, Sm and Ho, versus the common impurity metals; Al, Fe and Th, was determined in sulfuric acid media. The chelating resins all displayed a similar selectivity with Fe and Th adsorbed in preference to the REE and Al (i.e. Th≃Fe≫REE≃Al). The IDA resin displayed a far superior performance compared to both phosphonic resins (SP and AP) as well as a strong acid cation exchange resin for the adsorption of REE in the presence of very high Na or Ca concentrations. Equilibrium and kinetic adsorption isotherms for La were measured and successfully modelled with all resins, and the elution characteristics of selected resins investigated in both batch and column operation. A number of areas were identified where these resins could be exploited to provide an advantage in the hydrometallurgical processing of REE.