New phosphoramides containing imidazolidine moiety as anticancer agents: An experimental and computational study.

In this study, two new phosphoramides containing imidazolidine; diphenyl (2-imidazolidinone-1-yl)phosphonate (DIOP) and diphenyl (2-Imidazolidinethione -1-yl)phosphonate (DITP) as cytotoxic agents, were synthesized and characterized by using IR, 1H NMR, 13C NMR, 31P NMR, Mass spectroscopy and elemental analysis. The target products were obtained in moderate to good yields (69-86%) by using the time (3 h) and solvent (MeCN). The crystal structure of DIOP was investigated using X-ray crystallography. The main non-covalent intermolecular interactions were also studied by Hirshfeld surface analysis and fingerprint plots. The anticancer and growth inhibitory activities of the synthesized compounds were investigated against human breast cancer cell line MDA-MB-231 using MTT assay; DITP was found to be a better cytotoxic agent than DIOP. The cytotoxicity results were supported by a molecular docking study and in order to know the structure-activity relationship (SAR) of synthesized compounds, the values of HOMO and LUMO energies, dipole moments, hardness, softness, and electrophilicity index were investigated computationally by DFT method. These results were in good accordance with those of in vitro investigation and molecular docking study.

Therapeutic potential of phospho-thiadiazole derivatives as anti-glioblastoma agents: synthesis, biological assessment and computational study.

In this study, three new phospho thiadiazole compounds (A, F and W) were investigated as possible cytotoxic agents. The compounds were synthesised and characterised by using spectroscopy methods. The crystal structure of compound A was investigated using X-ray crystallography, since the title compounds can exist as different tautomeric forms, their conformational and geometrical aspects were investigated computationally by the DFT method. NBO analysis suggested that these compounds can function as appropriate ligands for the reaction with the nitrogen bases of DNA. All the synthesised compounds were evaluated in vitro for their cytotoxic activities against cancer in the human glioblastoma cell lines (U-251) using the MTT assay. According to the annexin V-FITC/PI results, a combination of synthesised compounds with ReoT3D showed a synergistic effect to increase the percentage of apoptotic cells. Molecular docking study for A (the most toxic compound) showed how it interacts with DNA. Both in vitro and in silico results showed that A has promising inhibitory potential (IC50: 48.1 ± 0.3 µM) and binding energy (-6.67 kcal/mol).

Synthesis, crystal structure, cholinesterase inhibitory activity, evaluation of insecticidal activities, and computational studies of new phosphonic acids.

In an attempt to obtain the modified and novel insecticides with low human toxicity, a series of novel mono-, bis-, and tetraphosphonic acid derivatives were designed and characterized by infrared, 1H, 13C, and 31P NMR spectroscopy and X-ray crystallography. The inhibitory effects of the synthesized compounds were evaluated using the in vitro Ellman method on human and insect acetylcholinesterase (AChE). Some of these compounds, which had low human and high insect toxicity, were chosen to assess the killing effects (in vivo) on third larval instar of elm leaf beetle (X. luteola). In vivo and in vitro evidence has revealed that bisphosphonic acids, containing hydrophobic systems, have a good selectivity of insect AChE inhibition. In the present study, docking results showed that bisphosphonic acids had lower binding energy and higher inhibition compared with tetraphosphonic acids due to the type of their topology and the ability of their hydrogen to interact with the catalytic triad (the main active site of the enzyme). Additionally, the QSAR results demonstrated that the major effecting factors on the insecticidal activity of the subject compounds are the hydrophobicity, size, shape, and ability to form a hydrogen bond. The present study can be helpful in the development of new insecticides.

Monophosphoramide derivatives: synthesis and crystal structure, theoretical and experimental studies of their biological effects.

Synthesizing new chemical compounds and studying their biological applications have been important issues in scientific research. In this investigation, we synthesized and characterized ten new N-acetyl phosphoramidate compounds and explored the crystal structure of three others. Furthermore, not only were some kinetic inhibition parameters measured, like IC50, Ki, kp, KD for 7 compounds on human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), but also their hydrophobic parameter was determined by shake-flask technique. All compounds (number 1-10) were investigated for anti-bacterial activity against three Gram-positive and three Gram-negative bacteria, while chloramphenicol was used as a standard antibiotic. In order to find new insecticide, toxicities of 13 acephate (Ace)-derived compounds (number 20-32) were bioassayed on third larval instar of elm leaf beetle and Xanthogaleruca luteola. Additionally, screening in vivo tests revealed that two compounds had had the greatest insecticidal potential in comparison with others. It means these ones inhibited AChE (with mixed mechanisms) and general esterase more than the rest. According to ChE-QSAR models, the inhibitory potency for enzyme and bacteria is directly influenced by the electronic parameters versus structural descriptors. AChE-QSPR model of fluorescence assay indicated that the inhibitory power of AChE is primarily influenced by a set of electronic factors with the priority of: EHB > PL > δ(31P) versus structural descriptor (SA and Mv). Synthesizing new chemical compounds and studying their biological applications have been important issues in scientific research. Toxicities of 13 acephate (Ace)-derived compounds (number 20-32) were bioassayed on third larval instar of elm leaf beetle and Xanthogaleruca luteola. Insect-QSAR equations of these compounds, based on MLR and PCA, showed that non-descriptor net charge nitrogen atom (which was affected by the polarization of N-H group) had the greatest effect on insecticidal potential.

Synthesis, characterized, QSAR studies and molecular docking of some phosphonates as COVID-19 inhibitors.

The global coronavirus (COVID-19) outbreak has prompted scientists to discover a cure for the disease. So far, phosphorus-based drugs have been proposed. These drugs have good inhibitory activity against the main protease (Mpro). Hence, in order to introduce a group of inhibitors the coronavirus, 51 compounds containing different mono, bis, and tetra phosphonates as Remdesivir derivatives, 32 of which are new, were synthesized and characterized by 31P, 13C, and 1H NMR and IR spectroscopy. Their biological activities were also investigated by Molecular Docking, QSAR, and Pharmacophore. Van der Waals, hydrogen bonding, and hydrophobic interactions were studied for all compounds as well as binding energy (△G, Kcal/mole) and the inhibitory constant Ki (µM) obtained by Molecular Docking. The results showed that the topology of the ligands and the change of the different groups attached to them can be effective in the placement position in the active site of the enzyme (Glu 166 and Gln 189). And bisphosphonates have a high interaction tendency with Mpro COVID-19. Compound L24 was identified as the best inhibitor with the -6.38 kcal/mol binding energy. The quantitative structure-activity relationship (QSAR) findings demonstrated that the polarity and topology of molecules in all phosphonate derivatives were important parameters affecting the effecting on the binding energy and inhibitory ability of compounds. The DFT and pharmacophore results are in good accordance with those of QSAR and molecular docking. This study can be helpful to gain a better understanding of the interactions between the Mpro of virus and its inhibitors in order to attain drugs with more effect on coronavirus (COVID-19).

Evaluating anti-coronavirus activity of some phosphoramides and their influencing inhibitory factors using molecular docking, DFT, QSAR, and NCI-RDG studies.

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.

Synthesis, characterization, cytotoxicity studies, theoretical approach of adsorptive removal and molecular calculations of four new phosphoramide derivatives and related graphene oxide.

In this study, four novel phosphoramide ligands (L1-L4) are synthesized and characterized by 31PNMR, 1HNMR, 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 IC50 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 IC50 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 DMol3 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.

Mode of action of 3-butylidene phthalide as a competent natural pesticide.

In this study, the biological activities and mode of action of 3-butylidene phthalide (3-BPH) were studied. 3-BPH had a superior efficiency against microsclerotia of Macrophomina phaseolina compared to the commercial fungicide tricyclazole. The microsclerotia formation and pigmentation were inhibited at 100 µg/mL. Moreover, the fungicide exhibited in silico affinity toward trihydroxy naphthalene reductase (3HNR). Both 3-BPH and tricyclazole showed congruence in the orientation and interaction within the 3HNR active site. 3-BPH displayed a strong interaction with SER-164, TYR-178, and TYR-223, with estimated binding energy and inhibition constant of -6.78 kcal mol-1, and Ki = 12.6 µM, respectively. Furthermore, it showed in vitro and in silico inhibitory activity against Drosophila melanogaster acetylcholinesterase in a concentration-dependent manner with IC50 = 730 µg/mL. It also impaired Galleria mellonella phenol oxidase enzyme, which corresponds with the insect's immune system. Phytotoxicity of 3-BPH was evident against Lemna minor at 1000 µg /mL; nevertheless, it was nontoxic at the concentrations inhibiting M. phaseolina microsclerotia and dark pigments suggest that it may be safe for use on other plants at low doses. Further assays are wanted to develop 3-BPH as a novel crop protection compound.

Relations between Structural and Luminescence Properties of Novel Lanthanide Nitrate Complexes with Bis-phosphoramidate Ligands.

Five new bisphosphoramide-based LnIII nitrate complexes [La2(NO3)6L3I] n (1), [Ce2(NO3)6L3I] n (2), [Sm2(NO3)6L3II] n (3), Sm2(NO3)6L3III (4), and Er(NO3)3L2III (5) [LI = piperazine-1,4-diylbis(diphenyl phosphine oxide), LII = N, N'-(ethane-1,2-diyl)bis( N-methyl- P, P-diphenylphosphinic amide, and LIII = N, N'-(ethane-1,2-diyl)bis( P, P-diphenylphosphinic amide)] have been synthesized and characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis (TGA), and single crystal X-ray and powder diffractions. The results of the X-ray diffraction analysis revealed the new polymorph of LIII, and the structural diversity of the synthesized complexes in the solid state. Complexes 1-3 display two-dimensional coordination polymers (2D-CP), containing layers with honeycomb (6, 3) topology. In these 2D-CPs, each Ln center (La, Ce, and Sm in 1, 2, and 3, respectively) could be considered as a triconnected node, linked by three bridging bisphosphoramide ligands as two-connecting linkers. In contrast, 4 is a discrete binuclear complex, in which bidentate LIII ligand has two entirely different conformations: the syn chelating and the anti bridging. Cationic complex 5 shows the monomeric structure, where bidentate LIII adopts the syn-chelating conformation. A comprehensive luminescence investigation has been performed on free ligands and their corresponding complexes as well. The synthesized compounds display a variety of luminescence behavior, including the ligand-centered fluorescence in 1, 2, and 5, two distinct emission peaks in 1 and 2, characteristic Sm-centered f-f emission in 3 and 4, and excitation-dependent emission in LIII, 1, and 2. Furthermore, the time-dependent density functional theory (TD-DFT) study was carried out on the reported compounds to understand the nature of the emission peaks and the observed luminescence properties. The solid-state emission quantum yields of lanthanide complexes were also determined at different excitation wavelengths.

Synthesis, crystal structure and biological evaluation of new phosphoramide derivatives as urease inhibitors using docking, QSAR and kinetic studies.

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 IC50 = 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.

Toward the comprehensive calculations on the relationship between 1 H, 13 C, 31 P chemical shifts, 2 JPH , and the bonding structure of different phosphoryl benzamides.

A comprehensive investigation was performed on 1 H, 13 C, and 31 P nuclear magnetic resonance (NMR) chemical shifts (CSs) of phosphoryl benzamide derivatives (C6 H5 C(O)NHP(O)R1 R2 ), (R1 , R2  = aziridine [L1 ], azetidine [L2 ], pyrrolidine [L3 ], piperidine [L4 ], azepane [L5 ], 4-methylpiperidine [L6 ], propane-2-amine [L7 ], and 2-methylpropane-2-amine [L8 ]) by the gauge-independent atomic orbital method (GIAO) to find the most accordant level of theory with the experimental values. To achieve this goal, all the structures were optimized using the B3LYP, BP86, PBE1PBE, M06-2X, MPWB1K, and MP2 methods with 6-31+G* basis set. Computed structural parameters demonstrate that BP86 has the best agreement to the experimental values between the other methods. The def2-TZVP and aug-cc-pVDZ basis sets were also employed to inspect the effect of different types of basis sets with higher polarization and diffuse functions. The correlation between the empirical and computational values attests that 6-31+G* basis set is the optimum case regarding minimization of the costs and results. The comparison between calculated and experimental CSs at all mentioned combinations illustrated that in accordance with structural results, the best level of theory in CSs is also BP86/6-31+G*. Besides, 2 JPH values were computed with an acceptable agreement to experimental data at the optimum level of theory. The dependency between 2 JPH and the bonding structure of studied ligands was also scrutinized by the Natural Bond Orbital (NBO) analysis that interprets the relationship between the electronic properties and 2 JPH values.

Synthesis, crystal structure, insecticidal activities, molecular docking and QSAR studies of some new phospho guanidines and phospho pyrazines as cholinesterase inhibitors.

Novel phospho guanidine and phospho pyrazine derivatives were synthesized and characterized by 31P, 13C, 1HNMR and IR spectroscopy to obtain novel and human-safe insecticides. Compound 35 [(C4H4N2NH)2P(O)(C6H6)] was investigated by X-ray crystallography. The inhibitory effects of synthesized compounds were evaluated on human and insect acetylcholinesterase (AChE) using in vitro Ellman method. A few of these compounds, which had low human toxicity, were selected for assessing the killing effects (in vivo) on the elm leaf beetle (X.luteola). The in vitro and in vivo results indicated that compounds bearing both phosphoryl groups and aromatic systems were found to possess a good selectivity for the inhibition of insect AChE over human AChE; up to 550-fold selectivity was achieved for compound 19. Docking studies were performed to explain reasons for the selective behavior of AChE inhibitors. Additionally, the quantitative structure-activity relationship (QSAR) and density functional theory (DFT) results of AChEs demonstrated that the size, shape, dipole moment, and ability to form hydrogen bond played the main role in both models. In addition, the aromatic π - π interactions and charge of the amide nitrogen had a major effect on insecticidal activity of the compounds. The present research can be helpful to gain a better understanding of the interactions between the insect AChE and its inhibitors and introduces compounds which are capable of becoming human-safe insecticides.

Characterization of acetylcholinesterase from elm left beetle, Xanthogaleruca luteola and QSAR of temephos derivatives against its activity.

Insect acetylcholinesterase (AChE) is the principal target for organophosphate (OP) and carbamate (CB) insecticides. In this research, an AChE from third instar larvae of elm left beetle, Xanthogaleruca luteola was purified by affinity chromatography. The enzyme was purified 75.29-fold with a total yield of 8.51%. As shown on denaturing SDS-PAGE, the molecular mass of purified AChE was 70kDa. The enzyme demonstrated maximum activity at pH7 and 35°C. Furthermore, a series of temephos (Tem) derivatives with the general structure of P(O)XP(O) (1-44) were prepared, synthesized and characterized by 31P, 13C, 1H NMR and FT-IR spectral techniques. The toxicity of 36 new Tem derivatives was screened on the third instar larvae and the compound compound 1,2 cyclohexane-N,N'-bis(N,N'-piperidine phosphoramidate) exhibited the highest insecticidal potential. The method of kinetic analysis is applied in order to obtain the maximum velocity (Vmax), the Michaelis constant (Km) and the parameters characterizing the inhibition type for inhibitors with >75% mortality in preliminary bioassay. The inhibition mechanism was mixed and inhibitory constant (Ki) was calculated as 4.70µM-1min-1 for this compound. Quantitative structure-activity relationship (QSAR) equations of these compounds indicated that the electron orbital energy has major effect on insecticidal properties.

Synthesis, biological evaluation, QSAR study and molecular docking of novel N-(4-amino carbonylpiperazinyl) (thio)phosphoramide derivatives as cholinesterase inhibitors.

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.

Structural and electronic aspects of hydrogen bonding in two polymorphs of butylene-N,N'-bis(O,O'-diarylphosphoramidate).

The bisphosphoramidate (C(6)H(5)O)(2)P(O)NH(CH(2))(4)NHP(O)(OC(6)H(5))(2) crystallizes in two polymorphs, one (ndl) with a needle habit from tetrahydrofuran (THF)/ethanol and another (prm) which forms prisms from H(2)O/ethanol. The molecules in the two forms differ from each other in some torsion angles and the orientation of the diaminobutane bridge, although the differences between the similar bond lengths are not significant for the two polymorphs. The geometry optimizations at the B3LYP/6-31+G* level for isolated molecules show that the two conformers which exist in the crystalline state also represent local gas-phase energy minima. The decrease in the N-H distance from the optimized to the crystal structures has been described in terms of the decrease in electron density (ρ) at the bond-critical point (b.c.p.) of the N-H bond path when the molecule participates in hydrogen bonding, comparing the results of atoms-in-molecules (AIM) and natural bond orbital (NBO) analyses for fully optimized structures ndl and prm with their hydrogen-bonded model clusters.

Removal of lead contaminant from Cr surfaces by using H2O2/EDTA cleaner solution.

All industrial processes especially metal cleaning procedures dealing with dangerous solutions should be used as little as possible and their emission into the aquatic environment should be controlled. In this study, in order to find a proper and efficient cleaning process, lead pollution was removed from the solid matrix by using a cleaner solution containing EDTA and H2O2 as chelating and oxidizing agents respectively. An orthogonal array design (OAD), OA9, was employed as a chemometric method for the optimization of the procedure. The results of experiment revealed that, lead pollution (-3 g) at the predicted optimum condition can be effectively removed from the solid matrix during 4 minutes. Cleaning quality was checked by SEM/EDAX, ICP and UV spectroscopy methods. Finally, the results of this investigation showed that H2O2/EDTA system can be considered as a novel, safe and an efficient cleaning solution, due to its proper processing parameters.

Anti-cancer Activity of New Phosphoramide-functionalized Graphene Oxides: An Experimental and Theoretical Evaluation.

BACKGROUND: Graphene oxide (GO)-based systems are among the drug delivery systems and have drawn a lot of interest in the field of medicine. METHODS: In this work, two novel phosphoramides with the formulas of (NHCHCH2C(CH3)2NHC(CH3)2CH2P(S)(OEt)2 (L1) and (NHCHCH2C(CH3)2 NHC (CH3)2CH2P (O) (NHC6H5) (OC5H6) (L2) were synthesized and characterized by spectroscopic methods. Then, graphene oxide (GO) was functionalized by L1 and L2. FT-IR, XRD, FE- SEM/ MAP, and Zeta potential analyses were applied to confirm the synthesis of phosphoramide-functionalized graphene oxides (GO-L1 and GO-L2). Cytotoxicity of synthesized compounds was evaluated against breast cancer cell line (SK-BR-3) using MTT assay. Moreover, the flow cytometry assay was performed to evaluate the cell death mechanisms. RESULTS: The results showed that GO-L1 and GO-L2 had a more inhibitory effect against cancer cells than that of L1 and L2, and GO-L2 showed the highest cytotoxicity with an IC50 value of 38.13 µg/ml. Quantum calculations were employed to optimize structures. HOMO and LUMO energy values and physical adsorption of synthesized compounds were obtained by the DMol3 module in the Material Studio 2017. The docking studies were used to investigate the binding of L1, L2, GO-L1, and GO-L2 to DNA polymerase IIα. CONCLUSION: Anticancer activity of phosphoramide compounds was increased after attachment on the GO surface, and the docking studies' results were in good accordance with the experimental cytotoxicity results.

Composites based on alginate containing formylphosphazene-crosslinked chitosan and its Cu(II) complex as an antibiotic-free antibacterial hydrogel dressing with enhanced cytocompatibility.

Hydrogels based on chitosan or alginate biopolymers are believed to be desirable for covering skin lesions. In this research, we explored the potential of a new composite hydrogels series of sodium alginate (Alg) filled with cross-linked chitosan to use as hydrogel wound dressings. Cross-linked chitosan (CSPN) was synthesized by Schiff-base reaction with aldehydated cyclophosphazene, and its Cu(II) complex was manufactured and identified. Then, their powder suspension and Alg were transformed into hydrogel via ion-crosslinking with Ca2+. The hydrogel constituents were investigated by using FTIR, XRD, rheological techniques, and thermal analysis including TGA (DTG) and DSC. Moreover, structure optimization calculations were performed with the Material Studio 2017 program based on DFT-D per Dmol3 module. Examination of Alg's interactions with CSPN and CSPN-Cu using this module demonstrated that Alg molecules can be well adsorbed to the particle's surface. By changing the dosage of CSPN and CSPN-Cu, the number and size of pores, swelling rate, degradation behavior, protein absorption rate, cytotoxicity and blood compatibility were changed significantly. Subsequently, we employed erythromycin as a model drug to assess the entrapment efficiency, loading capacity, and drug release rate. FITC staining was selected to verify the hydrogels' intracellular uptake. Assuring the cytocompatibility of Alg-based hydrogels was approved by assessing the survival rate of fibroblast cells using MTT assay. However, the presence of Cu(II) in the developed hydrogels caused a significant antibacterial effect, which was comparable to the antibiotic-containing hydrogels. Our findings predict these porous, biodegradable, and mechanically stable hydrogels potentially have a promising future in the wound healing as antibiotic-free antibacterial dressings.

Fabrication and examination of polyorganophosphazene/polycaprolactone-based scaffold with degradation, in vitro and in vivo behaviors suitable for tissue engineering applications.

The present study aimed to synthesis a proper scaffold consisting of hydroxylated polyphosphazene and polycaprolactone (PCL), focusing on its potential use in tissue engineering applications. The first grafting of PCL to poly(propylene glycol)phosphazene (PPGP) was performed via ROP of ε-caprolactone, whereas PPGP act as a multisite macroinitiator. The prepared poly(propylene glycol phosphazene)-graft-polycaprolactone (PPGP-g-PCL) were evaluated by essential tests, including NMR, FTIR, FESEM-EDS, TGA, DSC and contact angle measurement. The quantum calculations were performed to investigate molecular geometry and its energy, and HOMO and LUMO of PPGP-g-PCL in Materials Studio2017. MD simulations were applied to describe the interaction of the polymer on phospholipid membrane (POPC128b) in Material Studio2017. The C2C12 and L929 cells were used to probe the cell-surface interactions on synthetic polymers surfaces. Cells adhesion and proliferation onto scaffolds were evaluated using FESEM and MTT assay. In vitro analysis indicated enhanced cell adhesion, high proliferation rate, and excellent viability on scaffolds for both cell types. The polymer was further tested via intraperitoneal implantation in mice that showed no evidence of adverse inflammation and necrosis at the site of the scaffold implantation; in return, osteogenesis, new-formed bone and in vivo degradation of the scaffold were observed. Herein, in vitro and in vivo assessments confirm PPGP-g-PCL, as an appropriate scaffold for tissue engineering applications.

Solid-state and gas-phase structures of two conformers of N-(4-methylphenyl)-N',N''-bis(morpholinyl) phosphoric triamide; insights from X-ray crystallography and DFT calculations.

A phosphoric triamide with the formula (4-CH(3)-C(6)H(4)NH)P(O)(NC(4)H(8)O)(2) has been synthesized and characterized. X-ray crystallography at 120 K reveals that the title compound is composed of two symmetrically independent molecules in the solid state. Density functional theory (DFT) calculations reveal that two conformers A and B are very close to each other from an energy point of view. Thus there is equal chance that the presence of two conformers in the lattice may lead to hydrogen-bonded chains with an ABABAB arrangement. Hydrogen bonds of the type O(P)...H-N (O(P) being the phosphoryl O atom) are established between the two conformers with binding energies of -18.8 and -20.3 kJ mol(-1) (at B3LYP/6-31+G*). The electronic delocalization LP(O(P)) → σ*(N-H), LP(O(P)) being the lone pair of O(P), leads to a decrease in the strength of the N-H bond during hydrogen bonding between the conformers. The charge density (ρ) at the bond critical point (b.c.p.) of N-H decreases by ∼0.012-0.014 e Å(-3) when the molecule participates in hydrogen bonding. This may explain the red shift of the ν(N-H) stretching frequency from a single molecule in the gas phase to a hydrogen-bonded one in the solid state.