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In this study, four novel phosphoramide ligands (L1-L4) are synthesized and characterized by 31 PNMR, 1 HNMR, MASS, and FT-IR spectroscopies. In vitro cell growth inhibition is studied by the MTT assay to evaluate the cytotoxicity of ligands against MCF-7 cell line; the result of the assay demonstrates that all ligands significantly suppress the proliferation of breast cancer cells in a concentration-dependent manner. The calculated IC 50 values are in the range of 3.6-10.77 µg ml -1 , of which the lowest value is attributed to L1. Then a facile approach was developed to functionalize graphene oxide (GO) surface by L1. The data which are obtained by XRD, FT-IR, and EDX analysis confirmed the deposition of phosphoramide on the surface of GO. The cell viability of GO-L1 compound at different concentrations is investigated in 24 h experiment. Excellent synergistic antitumor effects of GO and L1 lead to a decrease in IC 50 value up to 2.13 μg ml -1 . The Quantum calculations of compounds are used to study energies and HOMO and LUMO values, dipole moments (µ), global hardness (η), global softness (σ), and electrophilicity index (ω) using DMol 3 module in Material studio2017. The docking calculations are performed to describe the mode of the binding to DNA and DNA polymerase IIα. Adsorption calculations of ligands (L1-L4) on GO sheet in the presence of water showed that L1 and L2 were located on GO via π electrons of anisole ring. While, L3 and L4 were located on GO by π - π interactions of aniline ring., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In an attempt to achieve a new class of phosphoramide inhibitors with high potency and resistance to the hydrolysis process against urease enzyme, we synthesized a series of bisphosphoramide derivatives (01-43) and characterized them by various spectroscopic techniques. The crystal structures of compounds 22 and 26 were investigated using X-ray crystallography. The inhibitory activities of the compounds were evaluated against the jack bean urease and were compared to monophosphoramide derivatives and other known standard inhibitors. The compounds containing aromatic amines and their substituted derivatives exhibited very high inhibitory activity in the range of IC 50  = 3.4-1.91 × 10 -10  nM compared with monophosphoramides, thiourea, and acetohydroxamic acid. It was also found that derivatives with PO functional groups have higher anti-urease activity than those with PS functional groups. Kinetics and docking studies were carried out to explore the binding mechanism that showed these compounds follow a mixed-type mechanism and, due to their extended structures, can cover the entire binding pocket of the enzyme, reducing the formation of the enzyme-substrate complex. The quantitative structure-activity relationship (QSAR) analysis also revealed that the interaction between the enzyme and inhibitor is significantly influenced by aromatic rings and PO functional groups. Collectively, the data obtained from experimental and theoretical studies indicated that these compounds can be developed as appropriate candidates for urease inhibitors in this field., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

In this study, the synthesis and spectroscopic characterization of new phosphoramides based on 3-amino-5-methylisoxazole with the formula R2P(O)[NH-C4H4NO], R = C6H5O (1), C6H5 (2), RP(O)[NH-C4H4NO]2, R = C6H5O (3), CH3-C6H4O (4), C6H5NH (5), (C6H5)ClP(O)[NH-C4H4NO] (6) and two lanthanide complexes [Ln(2)2(NO3)3(EtOH)]·EtOH, Ln(III) = Ce (7) and Eu (8), have been reported. The structural study of (3) shows the presence of two conformers (crystallographically independent molecules) in the crystalline lattice, caused by different orientations of the phenyl and isoxazole rings. For (3), the intermolecular interactions have been studied by Hirshfeld surface analysis and fingerprint plots. Furthermore, the electronic and energy aspects of hydrogen bonds between molecules of (3) have been explored by density functional theory (DFT) calculations. X-ray crystallography of complexes (7) and (8) reveals that two phosphoramide ligands take part in coordination to the metal, one as monodentate from O(phosphoryl), and the other one as chelate through O(phosphoryl) and N(ring). The complexes are also composed of two conformers in the solid-state structure. Quantum theory of atoms in molecules (QTAIM) analysis discloses the electrostatic nature of the Ln-ligand interaction.

Novel (thio)phosphoramidate derivatives based on piperidincarboxamide with the general formula of (NH2-C(O)-C5H9N)-P(X=O,S)R1R2 (1-5) and (NH2-C(O)-C5H9N)2-P(O)R (6-9) were synthesized and characterized by (31)P, (13)C, (1)H NMR, IR spectroscopy. Furthermore, the crystal structure of compound (NH2-C(O)-C5H9N)2-P(O)(OC6H5) (6) was investigated. The activities of derivatives on cholinesterases (ChE) were determined using a modified Ellman's method. Also the mixed-type mechanisms of these compounds were evaluated by Lineweaver-Burk plots. Molecular docking and quantitative structure-activity relationship (QSAR) were used to understand the relationship between molecular structural features and anti-ChE activity, and to predict the binding affinity of phosphoramido-piperidinecarboxamides (PAPCAs) to ChE receptors. From molecular docking analysis, noncovalent interactions especially hydrogen bonding as well as hydrophobic was found between PAPCAs and ChE. Based on the docking results, appropriate molecular structural parameters were adopted to develop a QSAR model. DFT-QSAR models for ChE enzymes demonstrated the importance of electrophilicity parameter in describing the anti-AChE and anti-BChE activities of the synthesized compounds. The correlation matrix of QSAR models and docking analysis confirmed that electrophilicity descriptor can control the influence of the hydrophobic properties of P=(O, S) and CO functional groups of PAPCA derivatives in the inhibition of human ChE enzymes., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Twelve new compounds of acephate (Ace) analogues were synthesized and characterized by (31)P, (13)C, and (1)H NMR and IR spectroscopy. The probable insecticide potential of these compounds as well as 23 previously prepared molecules with a general skeleton of RC(O)-NH-P(O)X1X2 was predicted by PASS software. Docking analysis showed that hydrophobic interaction and hydrogen bonding were created between the functional groups of Ace derivatives and the receptor sites of acetylcholinesterase. PCA-QSAR indicated that the electronic descriptors are dominated in comparison with the structural descriptors. The experimental-QSAR (R(2) = 0.903 and VIF < 2.997) and DFT-QSAR (R(2) = 0.990 and VIF ≤ 10) models clarified that the net charge of functional groups contributes an important function in an inhibition mechanism. Validity and integrity of this model were confirmed by the LOO cross-validation method with q(2) = 0.940 and low residuals between the training and testing sets. The correlation matrix of DFT-QSAR model confirmed the molecular docking results.

In this study, two novel phosphoramides containing 2-Amino-1,4-naphthaquinone, O,O -diethyl (2-naphthaleneyl-1,4-dione)phosphoramidothioate (NPT) and N,N´- bis(2-naphthaleneyl-1,4-dione) phenylphosphonic diamide (NPA) as cytotoxic agents, were synthesized and characterized by using spectroscopic methods. The anticancer activities of the synthesized compounds were investigated against the human breast cancer cell line SK-BR-3 and normal cells PC12 using MTT assay. The resulting data showed that NPA with an IC 50 value of 6.384 μg/ml had a better inhibitory effect against cancer cells than NPT (IC 50 = 10.08 μg/ml). According to the annexin V‐FITC/PI results, after treating cancer cells with synthesized compounds for 24 h, the overall population of apoptotic cells increased from 14.96% in the control group to 97.45%, 75.58% in NPA and NPT -treated cells, respectively. Given these results, NPA and NPT have considerable toxicity and apoptosis-inducing ability against SK-BR-3. The cytotoxicity results were supported by a molecular docking study to compute the interactions between synthesized compounds and transcription factor DNA (PDB ID: 1bg1). In order to know the structure-activity relationship (SAR) of synthesized compounds, the values of the quantum-mechanical descriptors were investigated computationally by the DFT method, and the obtained results were then compared with Cyclophosphamide (CY) as a standard anticancer drug. These results were in good accordance with those of in vitro investigation and molecular docking study. Antibacterial study of phosphoramides against Gram-negative (Escherichia coli) and Gram-positive bacteria (Staphylococcus aureus) was carried out MIC, MBC and DDA methods. Additionally, the molecular docking study was performed for the interaction between E. coli beta-lactamase (PDB: 4HBT) and S. aureus beta-lactamase (PDB: 1MWU) with target compounds, the obtained results showed that these compounds are appropriate ligands for antibacterial activity against Staphylococcus aureus and Escherichia coli bacteria. [Display omitted] • Two novel phosphoramides containing 2-amino-1,4-naphthaquinone were synthesized and characterized. • Cytotoxicity studies revealed a notable dose- dependent against human breast cancer cells. • Synthesized compounds had a significant apoptosis-inducing ability at different concentrations. • DFT calculations and molecular docking simulation were applied to support the cytotoxicity results. • The obtained results showed that these compounds are appropriate for antibacterial activity. [ABSTRACT FROM AUTHOR]

In an effort to identify the factors that affect the reactivity of nitrogen mustards, we prepared two phosphoramide mustard derivatives in interaction with DNA. The activity of these drugs was compared to that of cyclophosphamide and phosphoramide mustard. The effect of drug interaction on DNA aggregation and condensation was investigated in aqueous solution under physiological conditions, using a constant DNA concentration (6.25 mM) and various ligand/polynucleotide (phosphate) ratios of 1/160, 1/80, 1/40, 1/20, 1/10, 1/5, 1/2, and 1/1. Fourier transform infrared, two-dimensional infrared (2D IR), and ultraviolet (UV)-visible spectroscopic methods were used to determine the ligand binding modes, the binding constants, and the stability of the drug–DNA complexes in aqueous solution. Density functional theory (DFT) calculations followed by a natural bond orbital (NBO) analysis, Fukui functions, electron localization functions (ELF), generalized valence bond (GVB) calculations, and quantum theory of atoms in molecules (QTAIM) were used to find the relationship between the structure and reactivity of phosphoramide mustard derivatives. Together with these methods, docking studies were applied to understand the features that dominate the molecular orbitals, charges, and other binding parameters. Theoretical results that coincided with the experimental values were obtained under similar conditions of pH and temperature. The results showed that the reactivity of these compounds is controlled by the frontier molecular orbitals, as well as the factors affecting them, such as negative hyperconjugation. [ABSTRACT FROM AUTHOR]

Two new diorganotin complexes with formula {SnCl 2 (CH 3 ) 2 L1} 2 (C1), L1 = N-nicotinyl, N′,N″-bis(diethylamine) phosphoric triamide and {SnCl 2 (CH 3 ) 2 L2} n (C2), L2 = N-nicotinyl, N′,N″-bis(cyclopentylamine) phosphoric triamide were synthesized and characterized by IR and NMR spectroscopy, and elemental analysis. Single crystal X-ray diffraction structural analyses confirmed all-trans and cis–trans configurations for distorted octahedral geometry in C1 and C2, respectively. Also, it revealed that the coordination of L1 and L2 to Sn atom results to a binuclear arrangement in C1 and one-dimensional polymeric chain in C2. The relative stability of M1 (SnCl 2 (CH 3 ) 2 L1) and M2 (SnCl 2 (CH 3 ) 2 L2) units in binuclear and polymeric arrangements were compared using density functional theory (DFT) calculations. Based on theoretical findings, M1 and M2 prefer polymeric chain structure from energy point of view though the stability difference of M1, in two arrangements, was much lower compared to stability difference of M2. Furthermore, nature of bonds and Sn–ligand interactions was studied by NBO analyses. In vitro cytotoxic assay of complexes against breast cancer cell lines MCF-7, MDA-MB-468 and T47-Dhuman, were also reported. MDA-MB-468 cells are exquisitely sensitive to cell death induced by C1 and C2 complexes treatment. C1 complex exhibited higher anticancer activity, compared to C2, which can be attributed to larger Cl Sn Cl angle in C1. [ABSTRACT FROM AUTHOR]

Phosphorus and nitrogen-containing compounds widely are used as flame retardant for cotton fabrics. In this paper, two new phosphoramides with the formula of (C 6 H 5) 2 P(O)[N–C 3 H 5 N 2 O] (DIO) and (C 6 H 5) 2 P(O)[N–C 3 H 5 N 2 S] (DIT) were synthesised and characterised using 1H NMR, 13C NMR, 31P NMR, IR, and MASS spectroscopy. Crystal structures of DIO were investigated using X-ray crystallography to confirm the proposed structure. Experimental analyses such as VFT, LOI, SEM-EDS, TGA-DTG and cone caloriometer, indicated these compounds are noteworthy because of their thermal and flame retardancy properties. According to the cone calorimetric results, DIT/ cotton owning THR (18.26) and HRR (183.37) is better flame retardant than DIO/ cotton. After treatment with DIO and DIT , the mechanical properties of cotton decreased and improved slightly, respectively. In order to understand the Structure-Flame retardancy Relationship (SFR) of synthesized compounds, the values of HOMO and LUMO energies, dipole moments, hardness, softness, and electrophilicity index were investigated computationally by density functional theory (DFT) method. These results were in good accordance with those of flame retardancy investigation. • Two new phosphoramides were synthesised and characterised using spectroscopy techniques. • The thermal stability of phosphoramides were evaluated on cotton. • Flame retardant properties of phosphoramides were studied on cotton using cone calorimeter test. • Physical properties of phosphoramide-treated cotton fabrics were investigated. [ABSTRACT FROM AUTHOR]

A novel Zn(II) coordination polymer of N -nicotinyl phosphoric triamide ligand, {[Zn(L) 2 (H 2 O) 2 ]⋅(NO 3 ) 2 } n C1 (L = 3-NC 5 H 4 C(O)NHP(O)(NC 6 H 12 ) 2 ), has been synthesized and characterized by IR and 1 H, 13 C, 31 P NMR spectroscopy. Crystal structure analysis of C1 demonstrates a distorted octahedral geometry for Zn(II) ions. The oxygen atom of phosphoryl group (O phosphoryl ) and the nitrogen atom of pyridine ring (N pyridine ) of ligand take part in coordination to Zn(II) centers in a bidentate bridging mode. This coordination pattern results in infinite 1D polymeric chains along c axis, which are composed of metal shared 16-membered puckered rings. Structural data show that despite binding through O phosphoryl , the P O bond distance unexpectedly shortens in C1 when compared to that of the ligand, conceivably due to the steric factors in the solid state. This is confirmed by comparing the structural and electronic properties of C1 and L in the gas phase by using density functional theory (DFT) calculations. Natural bond orbital (NBO) analysis reveals the metal–ligand interaction for C1 as donor–acceptor type delocalizations (charge transfer). Besides, on the basis of the quantum theory of atoms in molecules (QTAIM) analysis, the nature of Zn O and Zn N bondings is found to be mainly electrostatic with a small amount of covalent character. [ABSTRACT FROM AUTHOR]

A novel zwitterionic bisphosphoramide compound with formula [4-NH-C5H4C(O)NHP(O)O-]2O•(H3O+)2 (H2O)2 was synthesized and characterized by NMR and FT-IR spectroscopy. The 31P{¹H} NMR spectrum illustrates a singlet peak at -16.51 ppm that is indicative of the structural symmetry. Also, the crystal structure of the title compound was determined by X-ray crystallography. In this structure there is one bisphosphoramide dianion BS two H3O+ cations that are co-crystallized with two H2O molecules. In the bisphosphoramide dianion, the two phosphorus atoms are connected to each other through an oxygen atom with P1-O3-P2 angle of 133.40(13)°. Intermolecular P-O. . . H-N, C=O. . . H-N and H-O. . . H-O hydrogen bonds led to a three dimensional network in the crystalline lattice. DFT computations were performed on the X-ray crystal structure and also on assumed cis and trans conformations of the two P-NR groups using Gaussian 98 software at B3LYP/6-31G* level of theory. The optimizations yielded identical pseudo-trans conformation for the both optimized cis and trans forms. [ABSTRACT FROM AUTHOR]

In this study, the synthesis and spectroscopic characterization of new phosphoramides based on 3-amino-5-methylisoxazole with the formula R2P(O)[NH-C4H4NO], R = C6H5O (1), C6H5 (2), RP(O)[NH-C4H4NO]2, R = C6H5O (3), CH3-C6H4O (4), C6H5NH (5), (C6H5)ClP(O)[NH-C4H4NO] (6) and two lanthanide complexes [Ln(2)2(NO3)3(EtOH)]·EtOH, LnIII = Ce (7) and Eu (8), have been reported. The structural study of (3) shows the presence of two conformers (crystallographically independent molecules) in the crystalline lattice, caused by different orientations of the phenyl and isoxazole rings. For (3), the intermolecular interactions have been studied by Hirshfeld surface analysis and fingerprint plots. Furthermore, the electronic and energy aspects of hydrogen bonds between molecules of (3) have been explored by density functional theory (DFT) calculations. X-ray crystallography of complexes (7) and (8) reveals that two phosphoramide ligands take part in coordination to the metal, one as monodentate from Ophosphoryl, and the other one as chelate through Ophosphoryl and Nring. The complexes are also composed of two conformers in the solid-state structure. Quantum theory of atoms in molecules (QTAIM) analysis discloses the electrostatic nature of the Ln-ligand interaction. [ABSTRACT FROM AUTHOR]

Novel nanocomposite films of chitosan/phosphoramide/Ag NPs were prepared containing 1-5% of silver nanoparticles. The Ag NPs were synthesized according to the citrate reduction method. The XRD and SEM analysis of Ag NPs, chitosan (CS), phosphoramide (Ph), CS/Ph, CS/Ag NPs films and the nanocomposite films 1-5 containing CS/Ph/1-5% Ag NPs were investigated. The in vitro antibacterial activities were evaluated against four bacteria including two Gram-positive Staphylococcus aureus (S. aureus), Bacillus cereus (B. cereus) and two Gram-negative Escherchia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa) bacteria. Results revealed greater antibacterial effects of the films against Gram-positive bacteria. Also, nanocomposite films containing higher percent of Ag NPs showed more antibacterial activities. [ABSTRACT FROM AUTHOR]

Abstract: A new diorganotin complex with formula {SnCl2(CH3)2 L} n (1), L = N-isonicotinyl, N ′,N ″-bis(α-methylbenzyl) phosphoric triamide, was synthesized and characterized on the basis of elemental analysis, IR and multinuclear NMR spectroscopy. Solid state structure of 1 was established by single crystal X-ray diffraction, revealing a distorted octahedral geometry for Sn, with trans-(dimethyl), cis-(Cl2) and cis-(L 2) configuration. Coordination of L from Ophosphoryl and Npyridine, as a bridging bidentate ligand, resulted in infinite 1D polymeric chains along b axis. Non-covalent interactions, i.e. hydrogen bonding, π–π stacking and CH⋯HC contacts further connected the chains into a 3D framework. The main intermolecular interactions were supported by Hirshfeld surface analysis and fingerprint plots. Density functional theory (DFT) calculations were performed for 1 and its possible all-trans isomer to compare their relative stability and results showed that the latter is the stable form in the gas phase. By using parameters derived from the quantum theory of atoms in molecules, the nature of Sn–ligand interaction is found to be mainly electrostatic with a small amount of covalent character. Natural bond orbital analysis showed donor–acceptor delocalizations from donor atoms to tin center. [Copyright &y& Elsevier]

• Docking interaction of a series of phosphoramides with COVID-19 was studied. • Phosphoramide inhibitors exhibited close interaction with COVID-19. • QSAR, DFT were used to study the inhibition affecting factors of Mpro activity. • Aromaticity is a major contributing factor to the inhibitory effect of compounds. The recent prevalence of coronavirus disease in 2019 (COVID-19) has triggered widespread global health concerns.Antiviral drugs based on phosphoramides have significant inhibitory activity against the main protease (Mpro) of the virus and prevent transcription and viral replication. Hence, in order to design and introduce a group of inhibitors affecting the coronavirus, 35 phosphoramide compounds based on phospho-guanine and phospho-pyrazine derivatives were selected for molecular docking study. The results showed that most phosphoguanides containing the amino benzimidazole have a high interaction tendency with COVID-19. Among them, compound 19 was identified as the strongest inhibitor with the -9.570 kcal/mol binding energy whereas, the binding energy of Remdesivir is -6.75 kcal/mol. The quantitative structure-activity relationship (QSAR) results demonstrated that the number of aromatic rings, amide's nitrogens and their ability in π-staking, and hydrogen interactions with Mpro active sites are major factors contributing to the inhibitory activity of these compounds.Also, the NCI-RDG and DFT results were in good accordance with those of QSAR and molecular docking. The findings of this investigation can be underlying the synthesis of effective and efficient drugs against COVID-19. [Display omitted] [ABSTRACT FROM AUTHOR]