Unravelling performance of honeycomb structures as drug delivery systems for the isoniazid drug using DFT-D3 correction dispersion and molecular dynamic simulations.

In this study, the potential of aluminum nitride (h-AlN), boron nitride (h-BN) and silicon carbide (h-SiC) nanosheets as the drug delivery systems (DDS) of isoniazid (INH) was scrutinized through density functional theory (DFT) and molecular dynamic (MD) simulations. We performed DFT periodic calculations on the geometry and electronic features of nanosheets adsorbed with INH by the DFT functional (DZP/GGA-PBE) employed in the SIESTA code. In the energetically favorable model, an oxygen atom of the C-O group of the INH molecule interacts with a Si atom of the h-SiC at 2.077 Å with an interaction energy of -1.361 eV. Charge transfer (CT) calculation by employing the Mulliken, Hirshfeld and Voronoi approaches reveals that the monolayers and drug molecules act as donors and acceptors, respectively. The density of states (DOS) calculations indicate that the HOMO-LUMO energy gap (HLG) of the h-SiC nanosheet declines significantly from 2.543 to 1.492 eV upon the adsorption of the INH molecule, which causes an electrical conductivity increase and then produces an electrical signal. The signal is linked to the existence of INH, demonstrating that h-SiC may be an appropriate sensor for INH sensing. The decrease in HLG for the interaction of INH and h-SiC is the uppermost (up to 41%) representing the uppermost sensitivity, whereas the sensitivity trend is σ(h-SiC) > σ(h-AlN) > σ(h-BN). Quantum theory of atoms in molecules (QTAIM) investigations is employed to scrutinize the nature of the INH/nanosheet interactions. The QTAIM analysis reveals that the interaction of the INH molecule and h-SiC has a partially covalent nature, while INH/h-AlN model electrostatic interaction occurs in the system and noncovalent and electrostatic interaction for the INH/h-BN model. Finally, the state-of-the-art DFT-MD simulations utilized in this study can mimic ambient conditions. The results obtained from the MD simulation show that it takes more time to bond the INH drug and h-SiC, and the INH/h-SiC system becomes stable. The results of the current research demonstrate the potential of h-SiC as a suitable sensor and drug delivery platform for INH drugs to remedy tuberculosis.

Preparation of Some New Pyrazolo[1,5-a]pyrimidines and Evaluation of Their Antioxidant, Antibacterial (MIC and ZOI) Activities, and Cytotoxic Effect on MCF-7 Cell Lines.

This study aims to synthesize some novel pyrazolo[1,5-a]pyrimidine derivatives, and investigate their biological activities. These compounds exhibited good to high antioxidant activities [2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capabilities]. Among them, Ethyl 5-(2-ethoxy-2-oxoethyl)-7-hydroxy-2-methylpyrazolo[1,5-a]pyrimidine-3-carboxylate (3h) showed the highest antioxidant activity [Half-maximal Inhibitory Concentration (IC50 )=15.34 µM] compared to ascorbic acid (IC50 =13.53 µM) as a standard compound. Their antibacterial activities were investigated against two Gram-positive bacteria (Bacillus subtilis, and Staphylococcus aureus) and two Gram-negative bacteria (Pseudomonas aeruginosa, and Escherichia coli). The results showed that Ethyl 7-hydroxy-5-phenylpyrazolo[1,5-a]pyrimidine-3-carboxylate (3i) has the best antibacterial activity against Gram-positive B. subtilis [Zone of Inhibition (ZOI)=23.0±1.4 mm, Minimum Inhibitory Concentration (MIC)=312 µM]. Also, the cytotoxicity of these compounds was assessed against breast cancer cell lines [human breast adenocarcinoma (MCF-7)], which 7-Hydroxy-2-methyl-5-phenylpyrazolo[1,5-a]pyrimidine-3-carbonitrile (3f) displayed the most cytotoxicity (IC50 =55.97 µg/mL), in contrast with Lapatinib (IC50 =79.38 µg/mL) as a known drug.

A new benzothiazole azo dye colorimetric chemosensor for detecting Pb2+ ion.

In this work, a new benzothiazole azo dye sensor (BTS) was synthesized, and its cation binding affinity was studied using the colorimetric method, UV-vis, and 1H NMR spectral data. The results revealed that the sensor BTS exhibits a remarkable tendency for Pb2+ ion to perform spontaneous visual color change from blue (BTS) to pink (BTS + Pb2+), without any color change in the aqueous solutions of other cations such as Hg2+, Cu2+, Al3+, Ni2+, Cd2+, Ag+, Ba2+, K+, Co2+, Mg2+, Na+, Ca2+, Fe2+, and Fe3+ ions. The observed selectivity could be due to the formation of the complex (BTS + Pb2+), which led to a blue shift from 586 nm (BTS) to 514 nm (BTS + Pb2+) in the UV spectrum. The job's plot provided the stoichiometry ratio of the complex (BTS + Pb2+) to be 1:1. The limit of detection (LOD) of BTS for Pb2+ ion sensing was obtained at 0.67 µM. Additionally, the binding constant for BTS toward Pb 2+ ion was studied using the Benesi-Hildebrand equation. As a result of the BTS test paper strips investigations, it was found that the synthesized sensor BTS could be used as a rapid colorimetric chemosensor for the detection of the Pb2+ ions in the distilled, tap, and sea waters.

A Selective and ''Off-On'' Fluorescent Chemosensor Based on Fluorescein for Al3+: Synthesis, Characterization, Spectroscopy Analyses, and DFT Calculation.

An efficient fluorescent cation chemosensor based on fluorescein L4 was well prepared and identified with spectroscopy analyses. UV-vis and fluorescence measurements examined the analyte complexation of the L4 with various cations, demonstrating a clear tendency to Al3+ ion. In the Job plot study, a stoichiometry ratio of a complex between L4 and Al3+ ion was determined to be 1: 2 (L4: Al3+). A stoichiometry ratio of complex between L4 and Al3+ ion was determined to be 1: 2 (L4: Al3+) using the Job plot. The association constant (Ka) of the L4-Al3+ complex was found 2.8 × 107 M-2. The obtained limit of detection (LOD) value (1.37 × 10-6 M for Al3+) exhibited the considerable sensitivity of the chemosensor L4 to Al3+ ion. DFT/TD-DFT calculations have also been employed to support the binding mode and photophysical properties of the complexation of chemosensor L4 to Al3+ ion and also to investigate the enhancement of L4 fluorescence by Al3+ ion.

A new fluorescent boronic acid sensor based on carbazole for glucose sensing via aggregation-induced emission.

A water-soluble fluorescent sensor based on carbazole pyridinium boronic acid (CPBA) was designed and synthesized. Its structure has been confirmed by CHN and 1H and 13C NMR, FT-IR, and MS spectral data. Fluorescence studies of the synthesized chemosensor CPBA showed a selective ratiometric fluorescent response for glucose among different monosaccharides. The results specified that CPBA is a pH-sensitive sensor that behaves differently in the absence and presence of glucose in the pH range 4-10. The pH, DLS, Job's plot, UV-visible, and fluorescence titration studies showed that the selectivity of CPBA towards glucose is through the aggregation-induced emission (AIE) phenomenon. The fluorescence emission intensity of CPBA changes by more than 2100 fold by adding glucose, whereas it is 2 fold for fructose. The calculated binding constant value of CPBA for glucose (K = 2.3 × 106 M-1) is 85 times greater than for fructose, indicating the high affinity of the sensor for glucose.

Heteropolyacid coupled with cyanoguanidine decorated magnetic chitosan as an efficient catalyst for the synthesis of pyranochromene derivatives.

In this study, a novel nanocatalyst was successfully prepared by heteropolyacid immobilization of magnetic chitosan-cyanoguanidine composite and fully characterized by different analysis methods, including FTIR, XRD, TGA, SEM, and EDS. The catalytic activity of fabricated composite was examined in a one-pot three-component reaction, involving the diverse active methylene compounds, various aryl aldehydes, and malononitrile in water. The results revealed the efficient catalytic performance of composite, while all reactions proceeded smoothly and led to the formation of the corresponding pyranochromene derivatives in high to excellent yields.

Creatine@SiO2 @Fe3 O4 nanocomposite as an efficient sorbent for magnetic solid-phase extraction of escitalopram and chlordiazepoxide from urine samples through quantitation via HPLC-UV.

An efficient, cost-effective, and fast-synthesis method is presented in the current study to prepare magnetic nanoparticles covered by cheap and nitrogen-rich creatine. The hydrothermal method was used for the synthesis of the magnetic core. The prepared magnetic core was then covered by SiO2 and subsequently functionalized using creatine. The prepared creatine@SiO2 @Fe3 O4 was utilized as a sorbent in the magnetic solid-phase extraction of the selected antidepressants including escitalopram and chlordiazepoxide as the model drugs. The extracted drugs were desorbed by a suitable organic solvent and analyzed by high-performance liquid chromatography equipped with an ultraviolet detection system. The influence of different variables on the magnetic solid-phase extraction method was examined by the Plackett-Burman and Box-Behnken designs for screening and optimization, respectively. Under the obtained optimum conditions, the linear ranges of the method were found to be in the range of 1-500 µg L-1 . The limits of detection and limits of quantification were in the range of 0.27-0.63 µg L-1 and 0.89-1.93 µg L-1 for the selected analytes, respectively. Furthermore, the enrichment factors were found to be 79.8 and 92.7 for chlordiazepoxide and escitalopram, respectively. The method was successfully employed for the analysis of selected drugs in urine samples.

Remediation of pharmaceuticals from contaminated water by molecularly imprinted polymers: a review.

The release of pharmaceuticals into the environment induces adverse effects on the metabolism of humans and other living species, calling for advanced remediation methods. Conventional removal methods are often non-selective and cause secondary contamination. These issues may be partly solved by the use of recently-developped adsorbents such as molecularly imprinted polymers. Here we review the synthesis and application of molecularly imprinted polymers for removing pharmaceuticals in water. Molecularly imprinted polymers are synthesized via several multiple-step polymerization methods. Molecularly imprinted polymers are potent adsorbents at the laboratory scale, yet their efficiency is limited by template leakage and polymer quality. Adsorption performance of multi-templated molecularly imprinted polymers depends on the design of wastewater treatment plants, pharmaceutical consumption patterns and the population serviced by these wastewater treatment plants.

Synthesis and characterization of amino sulfonic acid functionalized graphene oxide as a potential carrier for quercetin.

In this investigation, a new nanocomposite as a nanocarrier based on functionalized graphene oxide was synthesized by reaction of tetraethylenepentamine and chlorosulfonic acid with functional groups on the surface of GO. The synthesized nanocomposite was characterized by FT-IR, XRD TGA, FE-SEM, EDAX, TEM, and AFM analysis. To explore the potential of nanocomposites in drug delivery, the loading and releases of quercetin as an anticancer drug were investigated. The result displayed that more than 90% of the drug was loaded on the nanocarrier and the release of the drug is depending on the pH of the environment such that the releases of the drug in Gastric and intestinal conditions were up to 50% and 30%, respectively. The analysis of toxicity effect on the normal and cancer cells indicated that the nanocarrier with the drug has potential for cancer cells therapy without cytotoxic effect on normal cells in IC50 concentration.

Preparation of New Spiropyrazole, Pyrazole and Hydantoin Derivatives and Investigation of Their Antioxidant and Antibacterial Activities.

In this study, the synthesis of new spiropyrazoles, pyrazole and hydantoin heterocycles is reported by three component reactions of parabanic acids, hydrazine derivatives, and phenacyl bromides in the presence of triphenylphosphine as a nucleophile and triethylamine as a base in good to high yields (69-91 %). Evaluation of the synthesized compounds revealed a good to excellent antioxidant activities (37.6-96.2 %) using DPPH inhibitory potency. Among these compounds, hydantoin derivatives displayed higher antioxidant activities (93.7-96.2 %) comparing with spiropyrazoles and pyrazoles. The obtained results showed that Cl and Br substituents on the phenyl ring increased antioxidant activities of the related heterocycles. The antibacterial activities of the synthesized compounds were examined against two Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and two Gram-positive (Staphylococcus aureus and Bacillus subtilis) bacteria. Among the synthesized heterocycles, 2-[1,3-dimethyl-2,5-dioxo-4-(2-oxo-2-phenylethyl)imidazolidin-4-yl]hydrazine-1-carbothioamide exhibited the excellent antibacterial activity against both Gram-positive and Gram-negative bacteria.

Discovery of a tetracyclic indole alkaloid that postpones fibrillation of hen egg white lysozyme protein.

Protein aggregation, such as amyloid fibril formation, is molecular hallmark of many neurodegenerative disorders including Alzheimer's, Parkinson's, and Prion disease. Indole alkaloids are well-known as the compounds having the ability to inhibit protein fibrillation. In this study, we experimentally and computationally have investigated the anti-amyloid property of a derivative of a synthesized tetracyclic indole alkaloid (TCIA), possessing capable functional groups. The fibrillation reaction of Hen White Egg Lysozyme (HEWL) was performed in absence and presence of the indole alkaloid. For quantitative analysis, we used Thioflovin T binding assay which showed ~50% reduction in fibril formation in the presence of 20 µM TCIA. Using TEM imaging, we observed a significant morphological change in our model protein in the presence of TCIA. In addition, we exploited FT-IR assay by which Amide I peak's shifting toward lower wavenumber was clearly observed. Using Molecular Docking, the interaction of the inhibitor (TCIA) with the protein's amyloidogenic region was modeled. Also, different biophysical parameters were calculated by Molecular Dynamics (MD) simulation. Various biochemical assays, conformational change, and hydrophobicity exposure of the protein during amyloid formation indicated that the compound assists HEWL to keep its native structure via destabilizing ß-sheet structure.

Ionic liquid-based antimicrobial materials for water treatment, air filtration, food packaging and anticorrosion coatings.

Efforts to widen the scope of ionic liquids applications across diverse research areas have flourished in the last two decades with developments in understanding and tailoring their physical, chemical, and biological properties. The promising applications of ionic liquids-based materials as antimicrobial systems is due to their ability and flexibility to be tailored in varying sizes, morphologies, and surface charges. Ionic liquids are also considered as greener materials. Common methods for the preparation of ionic liquid-based materials include crosslinking, loading, grafting, and combination of ionic liquids with other polymeric materials. Recent research focuses on the tuning of the biological properties to design novel ionic liquids-based antimicrobial materials. Here, the properties, synthesis and applications of ionic liquids and ionic liquids-based materials are reviewed with focus on antimicrobial activities applied to water treatment, air filtration, food packaging, and anticorrosion.

Synthesis, in silico, in vitro and in vivo evaluations of isatin aroylhydrazones as highly potent anticonvulsant agents.

In this study, a series of new isatin aroylhydrazones (5a-e and 6a-e) was synthesized and evaluated for their anticonvulsant activities. The (Z)-configuration of compounds was confirmed by 1H NMR. In vivo studies using maximal electroshock (MES) and pentylenetetrazole (PTZ) models of epilepsy in mice revealed that while most of compounds had no effect on chemically-induced seizures at the higher dose of 100 mg/kg but showed significant protection against electrically-induced seizures at the lower dose of 5 mg/kg. Certainly, N-methyl analogs 6a and 6e were found to be the most effective compounds, displaying 100% protection at the dose of 5 mg/kg. Protein binding and lipophilicity(logP) of the selected compounds (6a and 6e) were also determined experimentally. In silico evaluations of title compounds showed acceptable ADME parameters, and drug-likeness properties. Distance mapping and docking of the selected compounds with different targets proposed the possible action of them on VGSCs and GABAA receptors. The cytotoxicity evaluation of 6a and 6e against SH-SY5Y and Hep-G2 cell lines indicated safety profile of compounds on the neuronal and hepatic cells.

Toxicity and remediation of pharmaceuticals and pesticides using metal oxides and carbon nanomaterials.

The worldwide development of agriculture and industry has resulted in contamination of water bodies by pharmaceuticals, pesticides and other xenobiotics. Even at trace levels of few micrograms per liter in waters, these contaminants induce public health and environmental issues, thus calling for efficient removal methods such as adsorption. Recent adsorption techniques for wastewater treatment involve metal oxide compounds, e.g. Fe2O3, ZnO, Al2O3 and ZnO-MgO, and carbon-based materials such as graphene oxide, activated carbon, carbon nanotubes, and carbon/graphene quantum dots. Here, the small size of metal oxides and the presence various functional groups has allowed higher adsorption efficiencies. Moreover, carbon-based adsorbents exhibit unique properties such as high surface area, high porosity, easy functionalization, low price, and high surface reactivity. Here we review the cytotoxic effects of pharmaceutical drugs and pesticides in terms of human risk and ecotoxicology. We also present remediation techniques involving adsorption on metal oxides and carbon-based materials.

Novel magnetic lignosulfonate-supported Pd complex as an efficient nanocatalyst for N-arylation of 4-methylbenzenesulfonamide.

This study presents a novel, economical, and environmentally technique for synthesizing magnetic palladium complex conjugated to activated calcium lignosulfonate with triethylenetetramine (Fe3O4@lignosulfonate@triethylenetetramine@Pd complex (FLT-Pd complex)) as a practical and air-stable catalyst. FLT-Pd complex is used as a catalyst for the fabrication of 4-methyl-N-phenyl-benzenesulfonamide derivatives via N-arylation of 4-methylbenzenesulfonamide in good yields. Furthermore, because of the complex magnetic reparability and high stability, it could be removed easily from the reaction media using a magnet and reused 5 cycles without a remarkable loss of catalytic prowess.

Antibacterial and Cytotoxic Effects of Cyclodextrin-Triazole-Titanium Based Nanocomposite

Abstract In this paper, the antibacterial activity of triazole functionalized cyclodextrin (CD.Click) and cyclodextrin-triazole-titanium based nanocomposite (CD.COM) was evaluated. The results indicated that CD.Click and CD.COM perform a wide range of antibacterial activity against both gram positive (Staphylococcus aureus and Bacillus subtilis) and gram negative (Escherichia coli and Pseudomonas aeruginosa) bacteria. The cytotoxic effect of CD.COM was investigated in vitro on cancerous cell lines (cervical cancer, breast carcinoma and sarcoma osteogenic) and fibroblast cells by MTT assay. The cell viability evaluation confirmed that the growth of cancerous cells is inhibited in a dose and time dependent way without any significant effect on the normal fibroblast cells.

Removal of fluoride ion from aqueous solutions by titania-grafted ß-cyclodextrin nanocomposite.

TiO2-grafted ß-cyclodextrin nanocomposite was synthesized by treating the triazole modified ß-cyclodextrin with the amino functionalized titanium dioxide nanoparticles, and applied for removal of fluoride ion from aqueous media by batch technique. The structural changes of nanocomposite before and after fluoride sorption were characterized using BET, BJH, AFM, and elemental mapping based on EDX analyses. The adsorption parameters including pH, adsorbent dosage, contact time, temperature, initial fluoride ion concentration, and coexisting anions have been investigated to determine the optimal adsorption conditions. The experimental data were evaluated by the Langmuir, Freundlich, and Temkin isotherms, and the pseudo-first order, pseudo-second order, and intraparticle diffusion kinetic models. Evaluation of experimental data with adsorption isotherms, Langmuire (R2 = 0.9988 and Qmax = 48.78 mg g-1), Temkin (R2 = 0.9939), and Freundlich (nF = 2.73) reveals the high adsorption efficiency of nanocomposite and suggests a monolayer chemical adsorption for fluoride ions. The adsorption experimental data fitted well with the pseudo-second order kinetic model, suggesting that a chemical sorption is involved in the rate-determining step. Thermodynamic parameters (ΔG° < 0, ΔH° > 0 and ΔS° > 0) confirmed the spontaneity, feasibility, and endothermic nature of fluoride sorption. The nanoadsorbent was regenerated in NaOH solution and reused for three adsorption-desorption cycles. The adsorption results represented the nanocomposite as a potential adsorbent for the fluoride ions removal from aqueous solutions.

A new fluorene-based Schiff-base as fluorescent chemosensor for selective detection of Cr3+ and Al3.

2-((9H-fluoren-2-ylimino) methyl)phenol (F3) was synthesized by condensation reaction of 9H-fluoren-2-amine and 2-hydroxybenzaldehyde in EtOH and characterized by its melting point, 1H-,13C NMR and molecular mass. F3 exhibits a high selectivity for detection of Cr3+ and Al3+ ions as a fluorescent chemosensor and showed a single emission band at 536nm upon excitation at 333nm according to fluorescence emission studies. The addition of Cr3+ and Al3+ make a significant increase in fluorescent intensity at 536nm in CH3CN, while other metal ions have almost no influence on the fluorescence. The fluorescence enhancement was attributed to the inhibited CN isomerization and the obstructed excited state intra-molecular proton transfer (ESIPT) of compound F3. Job's plot and DFT calculations data showed that the binding stoichiometries of F3 with Cr3+ and Al3+ are 2:1. The association constants (Ka) for Cr3+ and Al3+ were calculated and found to be 8.33×104M-1 and 5.44×104M-1, respectively. The detection limits were also calculated for Cr3+ and Al3+ and found to be 2.5×10-7mol/L and 3.1×10-7mol/L, respectively.

Natural phosphate-supported Cu(ii), an efficient and recyclable catalyst for the synthesis of xanthene and 1,4-disubstituted-1,2,3-triazole derivatives.

Cu(NO3)2 supported on natural phosphate, Cu(ii)/NP, was prepared by co-precipitation and applied as a heterogeneous catalyst for synthesizing xanthenes (2-3 h, 85-97%) through Knoevenagel-Michael cascade reaction of aromatic aldehydes with 1,3-cyclic diketones in ethanol under refluxing conditions. It was further used for regioselective synthesis of 1,4-disubstituted-1,2,3-triazoles (1-25 min, 95-99%) via a three-component reaction between organic halides, aromatic alkynes and sodium azide in methanol at room temperature. The proposed catalyst, Cu(ii)/NP, was characterized using X-ray fluorescence, X-ray diffraction, Fourier-transform infrared spectroscopy, scanning electron microscopy, Brunauer-Emmett-Teller, Barrett-Joyner-Halenda and inductively coupled plasma analyses. Compared to other reports in literature, the reactions took place through a simple co-precipitation, having short reaction time (<3 hours), high reaction yield (>85%), and high recyclability of catalyst (>5 times) without significant decrease in the inherent property and selectivity of catalyst. The proposed protocols provided significant economic and environmental advantages.