Pi-pi Interactions Research Articles

Isoniazid-Isatin Hydrazone Derivatives: Synthesis, Antitubercular Activity and Molecular Docking Studies

This study examined the synthesis of isoniazid-isatin hydrazone derivatives 5-7, followed by an investigation on the in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv, and molecular docking. A yield of 81 - 92 % of these compounds was achieved, with structural characterization by spectroscopic methods (FTIR, NMR, HRMS). The in vitro antitubercular activity was evaluated against M. tuberculosis H37Rv, and the highest effect was observed in compound 7, with a minimum inhibitory concentration (MIC) of 0.017 mM, lower than rifampicin (MIC 0.048 mM), which served as the positive control. In addition, the molecular docking of 5-7 was performed to visualize the interaction of isoniazid-isatin hydrazone derivatives with the active site of InhA receptor, which was in agreement with the experimental data. The hydrogen bonding with Ser94 and pi-pi interaction with Phe41 and/or Phe97 on the InhA active site was pivotal for the antitubercular activity. HIGHLIGHTS Tuberculosis caused by Mycobacterium tuberculosis is one of the top ten leading causes of death globally The first and second lines of antituberculosis drugs are the prevalent treatment for this disease, but they show several drawbacks and are exacerbated by the occurrence of drug resistance The isoniazid-isatin hydrazone derivatives were designed through molecular hybridization and synthesized effectively and exhibited moderate to high activity against tuberculosis H37Rv Molecular docking study demonstrated that the hydrogen bonding with Ser94 and the pi-pi interaction with Phe41 and/or Phe97 are important for antitubercular activity GRAPHICAL ABSTRACT

In vitro study on the potential fungicidal effects of atorvastatin in combination with some azole drugs against multidrug resistant Candida albicans.

The resistance of Candida albicans to azole drugs represents a great global challenge. This study investigates the potential fungicidal effects of atorvastatin (ATO) combinations with fluconazole (FLU), itraconazole (ITR), ketoconazole (KET) and voriconazole (VOR) against thirty-four multidrug-resistant (MDR) C. albicans using checkerboard and time-kill methods. Results showed that 94.12% of these isolates were MDR to ≥ two azole drugs, whereas 5.88% of them were susceptible to azole drugs. The tested isolates exhibited high resistance rates to FLU (58.82%), ITR (52.94%), VOR (47.06%) and KET (35.29%), whereas only three representative (8.82%) isolates were resistant to all tested azoles. Remarkably, the inhibition zones of these isolates were increased at least twofold with the presence of ATO, which interacted in a synergistic (FIC index ≤ 0.5) manner with tested azoles. In silico docking study of ATO and the four azole drugs were performed against the Lanosterol 14-alpha demethylase enzyme (ERG11) of C. albicans. Results showed that the mechanism of action of ATO against C. albicans is similar to that of azole compounds, with a docking score (−4.901) lower than azole drugs (≥5.0) due to the formation a single H-bond with Asp 225 and a pi–pi interaction with Thr 229. Importantly, ATO combinations with ITR, VOR and KET achieved fungicidal effects (≥ 3 Log10 cfu/ml reduction) against the representative isolates, whereas a fungistatic effect (≤ 3 Log10 cfu/ml reduction) was observed with FLU combination. Thus, the combination of ATO with azole drugs could be promising options for treating C. albicans infection.

New insights on aging mechanism of microplastics using PARAFAC analysis: Impact on 4-nitrophenol removal via Statistical Physics Interpretation

The aging effects of Polyethylene terephthalate (PET) microplastics were studied under Fenton process and Seawater. This research work mainly focuses on the aging mechanism of PET microplastics under two different conditions and their effect of aging on the adsorption of organic contaminants. The results of optical microscopic images, Scanning Electron Microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), Raman Spectroscopy, carbonyl, carboxyl index, X-ray powder diffraction (XRD) and dissolved organic carbon (DOC) help to understand the aging mechanism of PET microplastics. Parallel factor analysis (PARAFAC) and two-dimensional correlation spectroscopy (2D-COS) were performed using 3D Excitation-Emission Matrix (3D-EEM) to understand the possible dissolved organic matter released during the Fenton process and seawater. The release of protein/phenol like components was observed in seawater whereas humic acid-like component was noted in the Fenton process. Later, the aged PET microplastics were tested for their adsorption capacity towards 4-nitrophenol at three different temperatures (15, 30 and 45 °C). The adsorption capacity of aged microplastics was found to be higher than the normal PET microplastics for all three different temperatures. Hydrogen bonding, n-pi interaction performed a significant role than pi-pi and hydrophobic interaction in the adsorption mechanism. A double layer with double energy model was found to be the best fit in the adsorption processes. The calculated adsorption energies (ΔE1, ΔE2) from the statistical physics modeling also confirms the physisorption mechanism. The above experimental results help to understand the behavior of microplastics at different aging period and how it acts as a carrier for pollutant in the marine environment.

Network Pharmacology Integrated with Molecular Docking Explores the Mechanisms of Naringin against Osteoporotic Fracture by Regulating Oxidative Stress.

Naringin (NG), as the most abundant component of Drynariae Rhizoma (Chinese name: Gusuibu), has been proved to be an antioxidant flavonoid on promoting osteoporotic fracture (OF) healing, but relevant research is scanty on the underlying mechanisms. We adopted target prediction, protein-protein interaction (PPI) analysis, Gene Ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and molecular docking to establish a system pharmacology database of NG against OF. Totally 105 targets of naringin were obtained, including 26 common targets with OF. A total of 415 entries were obtained through GO Biological Process enrichment analysis (P < 0.05), and 37 entries were obtained through KEGG pathway enrichment analysis with seven signaling pathways included (P < 0.05), which were primarily concerned with p53, IL-17, TNF, estrogen, and PPAR signaling pathways. According to the results of molecular docking, naringin is all bound in the active pockets of the core targets with 3–9 hydrogen bonds through some connections such as hydrophobic interactions, Pi-Pi stacked interactions, and salt bridge, demonstrating that naringin binds tightly to the core targets. In general, naringin may treat OF through multiple targets and multiple pathways via regulating oxidative stress, etc. Notably, it is first reported that NG may regulate osteoclast differentiation and oxidative stress through the expression of the core targets so as to treat OF.

Molecular Docking and ADME Study of Quinoline and Chalcone based Derivatives for Anti-Cancer Activity

Cancer is a big issue that affects people all over the world. It develops as a result of uncontrolled cell growth. The interaction between developed ligands and thymine phosphorylation was investigated in this study, which was computationally optimized. The aim of this study was to examine the anticancerous activity of designed ligands in thymine phosphorylation (PDB ID: 1UOU) in order to minimize the cost and time required to develop a novel anticancer drug with minimal side effects. All the designed ligands showed mild to excellent binding with proteins. Most of the ligands exhibited better interaction compared to reference compound Tamoxifen with pdb files. Some of the designed ligands among (1-7) in qunoline derivatives and (1-5) in Chalcone derivatives showed excellent docking scores with PDB file (1UOU) of thymine phosphorylation. All the designed ligands and Zinc databases were docked with 1UOU PDB files of protein, and it was found that out of twenty-five designed ligands in Qunoline series, ligand 25 showed the best binding (docking score −8.268) with 1UOU PDB of protein thymine phosphorylation. And that out of ten designed ligands in Chalcone series, ligand K1 showed the best binding (docking score −9.433) with 1UOU PDB of protein thymine phosphorylation. Docked ligand cavity of ligand ku 25 in qunoline series and K 9 in Chalcone series showed important hydrophobic/non-polar residues such as Ile199, Ile316, Trp119, Phe168, Ile198, Cys172, Tyr188, Tyr398, Tyr435, Phe343, Tyr60, Leu328, Leu171, and showed pi-pi interaction with Tyr326. Further wet laboratory studies are continued in our laboratory to confirm and find out the efficiency and activity of target compounds.

Chalcone derivatives ameliorate lipopolysaccharide-induced acute lung injury and inflammation by targeting MD2.

Acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) are known as the common causes of respiratory failure in critically ill patients. Myeloid differentiation 2 (MD2), a co-receptor of toll like receptor 4 (TLR4), plays an important role in LPS-induced ALI in mice. Since MD2 inhibition by pharmacological inhibitors or gene knockout significantly attenuates ALI in animal models, MD2 has become an attractive target for the treatment of ALI. In this study we identified two chalcone-derived compounds, 7w and 7x, as new MD2 inhibitors, and investigated the therapeutic effects of 7x and 7w in LPS-induced ALI mouse model. In molecular docking analysis we found that 7w and 7x, formed pi-pi stacking interactions with Phe151 residue of the MD2 protein. The direct binding was confirmed by surface plasmon resonance analysis (with KD value of 96.2 and 31.2 μM, respectively) and by bis-ANS displacement assay. 7w and 7x (2.5, 10 μM) also dose-dependently inhibited the interaction between lipopolysaccharide (LPS) and rhMD2 and LPS-MD2-TLR4 complex formation. In mouse peritoneal macrophages, 7w and 7x (1.25-10 μM) dose-dependently inhibited LPS-induced inflammatory responses, MAPKs (JNK, ERK and P38) phosphorylation as well as NF-κB activation. Finally, oral administration of 7w or 7x (10 mg ·kg-1 per day, for 7 days prior LPS challenge) in ALI mouse model significantly alleviated LPS-induced lung injury, pulmonary edema, lung permeability, inflammatory cells infiltration, inflammatory cytokines expression and MD2/TLR4 complex formation. In summary, we identify 7w and 7x as new MD2 inhibitors to inhibit inflammatory response both in vitro and in vivo, proving the therapeutic potential of 7w and 7x for ALI and inflammatory diseases.

Eco-friendly Biowaste-based natural surfactant for lyotropic assemblies and Bio-adsorbent for dye removal

Aggregation behavior of biowaste Litchi Chinensis (LC) seed in three different solvents of varying polarity [water (80), formamide (108), and glycerol (37)] has been studied. Nematic liquid crystalline phase has been obtained for studied systems as confirmed by a polarizing optical microscope (POM). Potential of the LC seeds has been checked to remove the Rhodamine B (RhB) dye from the wastewater. Effect of dye varying concentration (1 mg/L, 3 mg/L, 5 mg/L, 7 mg/L and 10 mg/L) varying pH (3,6 and 9), and contact time (0 to120 sec) on adsorption process have been evaluated. About 52% of dye removal efficiency is achieved with bare 50 mg adsorbent at pH≈ 6. Pseudo-first-order kinetics is found best fitted for the adsorption process (R2~0.98). Freundlich isotherm is found best fitted to the adsorption data which is also vindicated by a greater value of R2~0.95. Hydrogen bonding, electrostatic interactions, and pi-pi interaction between RhB and LC seeds (saponin) could be responsible for the adsorption process. These results indicate that LC seed can act as a perfect surfactant for lyotropic assemblies and also an effectual natural adsorbent for the dye adsorption and cleaning of aquatic systems.

Experimental investigation on vortex-induced vibration and solid-structure impact of a near-bottom horizontal flexible pipeline in oblique shear flow

Vortex-induced vibrations and solid-structure impacts of a horizontal flexible pipeline in the vicinity of a bottom wall boundary are experimentally investigated in a water flume. A neutrally-buoyant submerged pipe, with a length-to-diameter ratio of about 87 and fixed end supports, is subject to a shear flow with an oblique angle of 30°. The initial gap-to-diameter ratio between the wall and the pipe is equal to 0.2. A non-intrusive measurement with high-speed cameras is employed to simultaneously capture the space–time varying in-line and cross-flow vibrations in the normal flow reduced velocity range of 3–15 with a maximum Reynolds number of about 2780. Experimental results highlight new pipe equilibrium profiles and modal response branches being significantly broadened due to the wall proximity. Two solid-pipe impact features are discussed, including single-segment and two-segment alternating impacts depending on the dominant oscillation mode of the flexible pipe. Both the response amplitude and frequency increase with the reduced velocity, resulting in a more frequent impact with a greater impact force. A temporal evolution from a single point contact to a segment contact is observed for the two-segment alternating impact. Nevertheless, the lengths of the two contact segments are different as a result of the asymmetric response profile. In all cases, the pipe transversely impacts the bottom wall introducing a perturbation transmission along the pipe, which leads to the multi-mode, multi-frequency and asynchronous in-line and cross-flow oscillations with a 1:1 and 2:1 resonance. Due to a momentum energy consumption, the pipe experiences a slow post-impact bouncing phenomenon, contributing to a longer temporal period of the fluid–pipe interaction with a wall impact.

Analysis of Ground Movement during Large-Scale Pipe Roof Installation and Artificial Ground Freezing of Gongbei Tunnel

This paper analyzes the vertical ground movement during large-scale pipe roof installation and artificial ground freezing of Gongbei tunnel of the Hong Kong-Zhuhai-Macau bridge project. The transverse ground settlement during pipe roof installation is analyzed. The ground loss volume ratio and settlement trough width coefficient during pipe jacking are estimated based on the field measurement of ground settlement. The interaction of pipes during multiple jacking is investigated. The effect of frost heave control by pregrouting, limiting frozen soil thickness, and combination of the two methods is evaluated. The analysis shows that the ground settlement during pipe roof installation by jacking 37 pieces of 1620 mm steel pipes is relatively small with a maximum value of 2.2 cm. The reinforcement to ground provided by the fore-jacked pipes reduces the ground loss volume ratio and, consequently, the ground settlement during the follow-up pipe jacking. The artificial ground freezing generates a relatively large ground heave with a maximum value of 7.8 cm. Pregrouting plays a critical role in the frost heave control by reducing the heave by about 33%. Limiting the frozen soil thickness by heating pipes serves as an effective supplement to frost heave control by reducing the heave by about 9%. The combination of the two measures reduces the ground heave by about 42%. Findings from this paper provide valuable reference to the tunnel construction using pipe roof and artificial ground freezing as presupport.

Engineering of highly Brachychiton populneus shells@polyaniline bio-sorbent for efficient removal of pesticides from wastewater: Optimization using BBD-RSM approach

New biocomposite based on polyaniline and Brachychiton populneus shells (BP@PANI) was successfully synthesized through in situ chemical polymerization. The prepared composite was characterized using different analytical techniques such as scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), Fourier transform infrared spectroscopy (FTIR) and Brunauer-Emmett-Teller (BET) analysis. The BP@PANI material was effectively used as an adsorbent to remove thiabendazole (TBZ) and methyl parathion (MP) pesticides from wastewater. The kinetic and equilibrium results indicated that the adsorption process followed the pseudo-second-order model and the Langmuir isotherm. The optimum adsorption amounts were 255.39 and 78.59 mg.g−1 for TBZ and MP, respectively. The biosorption mechanism of both pesticides was evaluated and assigned to electrostatic interactions, pi-pi interactions and hydrogen bonding. The desorption study proved the excellent recycling of BP@PANI biosorbent. Moreover, the biosorption process was optimized by the response surface methodology combined with the Box Behnken design (RSM-BBD). The optimal parameters were found to be : Dose = 0.88 g.L−1, Ci = 5 mg.L−1 and Time = 100 min for TBZ and Dose = 1 g.L−1, Ci = 5 mg.L−1 and Time = 120 min for MP. The predicted elimination efficiency was determined to be 85% for TBZ and 84% for MP. The experimental data obtained were in good agreement with that predicted by the model, which indicates the importance of the RSM approach in terms of modeling and optimization.

Comparison of 3D Solid and Beam–Spring FE Modeling Approaches in the Evaluation of Buried Pipeline Behavior at a Strike-Slip Fault Crossing

Validated 3D solid finite element (FE) models offer an accurate performance of buried pipelines at earthquake faults. However, it is common to use a beam–spring model for the design of buried pipelines, and all the design guidelines are fitted to this modeling approach. Therefore, this study has focused on (1) the improvement of modeling techniques in the beam–spring FE modeling approach for the reproduction of the realistic performance of buried pipelines, and (2) the determination of an appropriate damage criterion for buried pipelines in beam–spring FE models. For this paper, after the verification of FE models by pull-out and lateral sliding tests, buried pipeline performance was evaluated at a strike-slip fault crossing using nonlinear beam–spring FE models and nonlinear 3D solid FE models. Material nonlinearity, contact nonlinearity, and geometrical nonlinearity effects were considered in all analyses. Based on the results, pressure and shear forces caused by fault movement and pipeline deformation around the high curvature zone cause local confinement of the soil, and soil stiffness around the high curvature zone locally increases. This increases the soil–pipe interaction forces on pipelines in high curvature zones. The beam–spring models and design guidelines, because of the uniform assumption of the soil spring stiffness along the pipe, do not consider this phenomenon. Therefore, to prevent the underestimation of forces on the pipeline, it is recommended to consider local increases in soil spring stiffness around the high curvature zone in beam–spring models. Moreover, drastic increases in the strain responses of the pipeline in the beam–spring model is a good criterion for a damage evaluation of the pipeline.

Type II c-Met inhibitors: molecular insight into crucial interactions for effective inhibition.

The c-Met tyrosine kinase plays an important role in human cancers. Preclinical studies demonstrated that c-Met is over-expressed, mutated and amplified in a variety of human tumor types and design of more potent c-Met inhibitors is a priority. In this study, 14 molecular dynamics simulations of potent type II c-Met inhibitors were run to resolve the critical interactions responsible for high affinity of ligands towards c-Met considering the essential flexibility of protein-ligand interactions. Residues Phe1223 and Tyr1159, involved in pi-pi interactions were recognized as the most effective residues in the ligand binding in terms of binding free energies. Hydrogen bond interaction with Met1160 was also found necessary for effective type II ligand binding to c-Met.

Prophylactic and therapeutic potential of selected immunomodulatory agents from Ayurveda against coronaviruses amidst the current formidable scenario: an in silico analysis

There is currently a dearth of specific therapies to treat respiratory infections caused by the three related species of coronaviruses viz. SARS-CoV-2, SARS-CoV and MERS-CoV. Prevention from disease is currently the safest and most convenient alternative available. The present study aimed to evaluate the preventive and therapeutic effect of fifteen phytoconstituents from medicinal plants of Ayurveda against coronaviruses by in silico screening. All the phytoconstituents exhibited rapid GI absorption and bioavailability and most of them had no toxicity versus reference drug chloroquine. BAS analyses revealed that most of the phytocomponents had favorable bioactivity scores towards biological target proteins. Principal component analysis revealed that most of the phytoconstituents fell close to chloroquine in 3D projection of chemical space. Affinity of phytoconstituents towards SARS-CoV-2 spike protein-human ACE2 complex decreased as isomeldenin > tinosporaside > EGCG whereas in case of unbound ACE2, the strength of binding followed the order isomeldenin > tinosporaside > ellagic acid. Towards SARS-CoV-2 main and papain-like proteases, the affinity decreased as isomeldenin > EGCG > tinosporaside and EGCG > tinosporaside > isomeldenin, respectively. Most phytoconstituents displayed significant binding kinetics to the selected protein targets than chloroquine. SAR analysis revealed that isomeldenin, tinosporaside, EGCG and ellagic acid bind to viral spike glycoproteins via H-bond, Pi-Pi, Pi-sigma and Pi-alkyl type interactions. Molecular dynamics simulation of isomeldenin and EGCG with SARS-CoV and SARS-CoV-2 spike glycoproteins exhibited low deviations throughout the 100 ns simulation indicating good stability and compactness of the protein-ligand complexes. Thus, the above four phytoconstituents have the potential to emerge as prophylactic and therapeutic agents against coronaviruses if investigated further in vitro and in vivo.

Rutin Increases Shear-Dependent TGF-β1 Activation By Interacting with Putative PDI Binding Sites: Role of Oxidation in Shear-Dependent TGF-β1 Activation

TGF-β1 is a very potent cytokine that, when activated, exerts both physiological and pathological functions, but the mechanism of activation remains unclear. Platelets contain 40-100-fold more TGF-β1 than other cell types and release TGF-β1 in an inactive latent complex comprised of mature TGF-β1 bound with latency-associated peptide and latent-TGF-β1 binding protein 1. We previously demonstrated that shear force activates latent TGF-β1 released from platelets in vitro, and that thiol-disulfide exchange contributes to this process. We also showed that protein disulfide isomerase (PDI) regulates shear-mediated TGF-β1 activation differentially, depending on whether PDI remains in its oxidized or reduced state. To test whether oxidation is required for latent TGF-β1 activation, we subjected platelet releasates to physiological shear/stirring for 2 hours in a closed chamber with room air or argon gas. We found ~10-fold increase in TGF-β1 activation compared to unsheared samples in room air, while the samples sheared under argon gas resulted in ~25% lower TGF-β1 activation (21 ± 1.0 % in room air vs. 16 ± 2.0 % of total TGF-β1 in argon gas, p=0.03). We also found that adding H2O2 to the platelet releasate resulted in increased shear-dependent TGF-β1 activation (active TGF-β1 was 16 ± 2.0 % in sheared samples and 22 ± 2.2 % of total TGF-β1 in sheared with H2O2 samples, p=0.03), indicating that oxidation during shear contributes to TGF-β1 activation. Since PDI can catalyze both oxidation and reduction of substrates, and because we previously showed that the reduced form of PDI inhibited shear-dependent TGF-β1 activation, we hypothesized that blocking the reduction function of PDI may increase shear-dependent TGF-β1 activation. To test this hypothesis, we assessed the effect of quercetin-3-rutinoside (rutin), a specific PDI inhibitor identified by high throughput screening, on shear-induced TGF-β1 activation. Rutin increased shear-induced TGF-β1 activation in a dose-dependent manner in that > 2.0 fold higher TGF-β1 activity was observed with 25 uM rutin, a concentration that blocked 55 to 80% of insulin reduction by PDI, confirming that rutin increases shear-dependent TGF-β1 activation by blocking the reduction function of PDI. We then assessed how rutin blocks PDI reduction function using PyMol modeling to identify the most likely interactions between rutin and PDI domains. After adjusting for the possible rotations of likely bond orientations, and considering minimum steric forces, the best model identified strong pi-pi interactions between Trp396 of the b' domain of PDI with the quercetin moiety of rutin (Figure-1). This interaction may stabilize the active site sulfhydryls of PDI so they maintain an inactive conformation, which buries the active site sulfhydryls, causing a loss in their solvent accessibility and thus inhibiting PDI's reductase function and increasing TGF-β1 activation. We conclude that thiol isomerases differentially regulate shear-dependent TGF-β1 activation. Thus, thiol-disulfide exchange regulator, such as PDI may be a potential target for suppressing or enhancing TGF-β1 activation. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A refined nonlinear analytical method for buried pipelines crossing strike‐slip faults

AbstractThis paper presents a novel nonlinear governing equation and solution procedure for analyzing a buried pipeline at an active strike‐slip fault crossing. The proposed method includes exact nonlinear axial and nonlinear transverse soil–pipe interaction terms, in addition to geometrical nonlinearity terms in the governing equation. The assumption of partitioning the pipeline into four segments with four governing equations based on the soil yield threshold is removed, and a unified governing equation is introduced. Compared with existing methods, the proposed method has a significantly extended application range with improved accuracy and provides the advantage of including the sliding of buried pipelines within soil, transverse soil spring plasticity, and improved large‐deformation effects including the sliding effect. The solution procedure is improved by removing the optimization steps and external calculations. The proposed method is verified by comparison to a verified finite element‐based model with various fault displacements and angles, and the results are in excellent quantitative and qualitative agreement with the numerical results, even for cases of large fault movement. Finally, criteria for assessing the ovalization damage of buried pipelines are proposed. The proposed method fulfills the missed part of literature, and it is valuable for (1) verification of the nonlinear FEM analysis; (2) fast, economic, and reliable stability analysis and design of buried pipelines; and (3) a strong tool for future developments of buried pipelines seismic design guidelines.

Interaction of acridinedione dye with a globular protein in the presence of site selective and site specific binding drugs: Photophysical techniques assisted by molecular docking methods

Photophysical investigations and molecular docking studies of photoinduced electron transfer (PET) based fluorophores of acridine family with a globular protein, Bovine Serum Albumin (BSA) bound to non-narcotic drugs like phenylbutazone (PB) and flufenamic acid (FA) were carried out in aqueous solution. PB and FA are site specific and site selective drugs, wherein PB predominantly binds at the site (I) whereas FA selectively orients towards site (II) of BSA. Acridinedione (AD) dyes, both resorcinol and dimedone based are hydrophobic in nature and exhibits a combination of both hydrophobic and hydrogen-bonding interactions that are based on the binding sites in BSA. The extent of displacement of AD from the binding sites of BSA by PB and FA are elucidated and established from variation in the fluorescence lifetime and relative amplitude distribution of free and dye bound in site (I) and site (II). The extent of binding affinity of PB-BSA and FA-BSA in the presence of AD is minimal when compared to other site I and II drugs. This is attributed to AD dye bound to several amino acid residues present in BSA such that the dye prefers multiple binding sites in BSA even in the presence of FA and PB. Further, the dye bound to several amino acid residues of BSA ascertains the combination of hydrogen-bonding, hydrophobic interactions, pi-pi and pi-alkyl interaction apart from the binding through sites (I) and (II) from molecular docking methods. The combination of fluorescence tools with molecular modelling techniques provides an excellent approach in determining the stability of these complexes containing competitive guest molecules in the presence of a fluorescence probe and the binding characteristics of dye in a micro heterogeneous environment.

Design of new drug delivery platform based on surface functionalization of black phosphorus nanosheet with a smart polymer for enhancing the efficiency of doxorubicin in the treatment of cancer.

The development of drug delivery systems (DDSs) has raised hopes for targeted cancer therapy. Smart polymers can be conjugated with several nanoparticles and increase their efficiency in biomedical applications. In this work, the classical molecular dynamics and well-tempered metadynamics simulations are performed to study the behavior of black phosphorus (BPH) nanosheet functionalized with polyethylenimine (PEI) in adsorption, diffusion, and release of doxorubicin (DOX) anticancer drug. Adsorption of the drug on PEI-BPH surface is mainly due to the formation of strong pi-pi interaction between the drug and BPH. The drug-binding to the nanosheet is enhanced by the intermolecular hydrogen bond that formed between DOX and PEI. The energy values for the interaction of DOX with BPH and PEI are calculated to be about - 180 and - 50 kJ/mol, respectively. The obtained results indicated that the adsorption of the drug molecules on the nanosheet destroyed the hydration layer around the BPH-PEI surface. The free energy calculation for DDS shows a global minimum in which the distances of DOX from BPH surface and PEI are about 1.0 and 0.5nm, respectively. Furthermore, the diffusion of DDS into the membrane has a macropinocytosis pathway that is in line with experimental observations. Moreover, it is found that, unlike the isolated DOX, the drug in complex with BPH-PEI can be easily penetrated membrane cells. The study of the pH-responsive release of the drug shows the high solubility of the polymer in the water environment plays the main role in swelling of DDS and the release of the DOX molecules.

Discrimination of dopamine by an electrode modified with negatively charged manganese dioxide nanoparticles decorated on a poly(3,4 ethylenedioxythiophene)/reduced graphene oxide composite

A unique nanocomposite was fabricated using negatively charged manganese dioxide nanoparticles, poly (3,4-ethylenedioxythiophene) and reduced graphene oxide (MnO2/PEDOT/rGO). The nanocomposite was deposited on a glassy carbon electrode (GCE) functionalized with amino groups. The modified GCE was used to electrochemically detect dopamine (DA). The surface morphology, charge effect and electrochemical behaviours of the modified GCE were characterized by scanning electron microscopy, energy dispersive X-ray analysis (EDX), cyclic voltammetry and electrochemical impedance spectroscopy, respectively. The MnO2/PEDOT/rGO/GCE exhibited excellent performance towards DA sensing with a linear range between 0.05 and 135 µM with a lowest detection limit of 30 nM (S/N = 3). Selectivity towards DA was high in the presence of high concentrations of the typical interferences ascorbic acid and uric acid. The stability and reproducibility of the electrode were good. The sensor accurately determined DA in human serum. The synergic effect of the multiple components of the fabricated nanocomposite were critical to the good DA sensing performance. rGO provided a conductive backbone, PEDOT directed the uniform growth of MnO2 and adsorbed DA via pi-pi and electrostatic interaction, while the negatively charged MnO2 provided adsorption and catalytic sites for protonated DA. This work produced a promising biosensor that sensitively and selectively detected DA.

Mechanical properties of CFRP-strengthened prestressed concrete cylinder pipe based on multi-field coupling

Broken prestressing wires in prestressed concrete cylinder pipe (PCCP) can cause incident of pipe burst. A method was proposed to repair damaged PCCP with broken wires by externally bonding carbon fiber reinforced polymer (CFRP). A finite element model was established and calibrated against the data from a prototype-scale laboratory test. Upon calibration, a three-dimensional numerical model was built to simulate the response of PCCP pipeline with five segments. Multi-field coupling was accomplished by Mesh-based parallel Code Coupling Interface (MpCCI) to incorporate the soil–pipe interaction and the effect of hydrodynamic pressure for PCCP. The effect of externally bonded CFRP to repair PCCP with broken wires was systematically analyzed. Results show that at a certain number of broken wires, the use of CFRP for pipe repair can significantly reduce the strains for each pipe component and increase the resilience of PCCP. The improved PCCP performance was assessed on the basis of crack visibility in the concrete core, and the deformation of the steel cylinder. The CFRP strain was much less than its ultimate strain, when cracks in the concrete core became visible and the steel cylinder yielded, suggesting that failure of PCCP could be ahead of CFRP.

Nonlinear static finite element analysis of sinking a floating pipeline to the bottom in calm water

ABSTRACT This paper describes a nonlinear static finite element analysis for simulating a process of submerging a floating pipeline to the bottom in calm water. Soil–pipe interaction elements, fully submerged pipe elements, partially submerged pipe elements, and floating pipe elements were used. Also, a load stiffness matrix associated with hydrostatic pressure was illustrated. Then, an incremental iterative procedure was developed to analyze large deformation of the pipeline during the sinking process and to take into account pipe-seabed interaction. The paper concentrates on the modeling of filled-in water loads and boundary conditions related to an offshore tugboat. Some numerical examples are provided to show the capabilities of the proposed analysis to model the continuous float-and-sink procedure of the pipeline.