ABSTRACT
Respiratory syncytial virus (RSV) is a major cause of serious lower respiratory tract infections in infants, children, and older persons. Currently, the only approved anti-viral chemotherapeutic drug for RSV treatment is ribavirin aerosol; however, its significant toxicity has led to restricted clinical use. In a previous study, we developed various benzimidazole derivatives against RSV. In this study, we synthesised 3-azide substituted furoxazine-fused benzimidazole derivatives by sulfonylation and azide substitution of the 3-hydroxyl group of the furoxazine-fused benzimidazole derivatives. Subsequently, a series of 3-(1,2,3-triazol-1-yl)-substituted furoxazine-fused benzimidazole derivatives were synthesised using the classical click reaction. Biological evaluations of the target compounds indicated that compound 4a-2 had higher activity against RSV (EC50 = 12.17 µM) and lower cytotoxicity (CC50 = 390.64 µM). Compound 4a-2 exerted anti-viral effects against the RSV Long strain by inhibiting apoptosis and the elevation of reactive oxygen species (ROS) and inflammatory factors caused by viral infection in vitro. Additionally, the clinical symptoms of the virus-infected mice were markedly relieved, and the viral load in the lung tissues was dramatically decreased. The biosafety profile of compound 4a-2 was also favourable, showing no detectable adverse effects on any of the major organs in vivo. These findings underscore the potential of compound 4a-2 as a valuable therapeutic option for combating RSV infections while also laying the foundation for further research and development in the field.
Subject(s)
Respiratory Syncytial Virus Infections , Respiratory Syncytial Virus, Human , Child , Mice , Humans , Animals , Aged , Aged, 80 and over , Azides/pharmacology , Antiviral Agents , Respiratory Syncytial Virus Infections/drug therapy , BenzimidazolesABSTRACT
The biopolymer lignin is deposited in the cell walls of vascular cells and is essential for long-distance water conduction and structural support in plants. Different vascular cell types contain distinct and conserved lignin chemistries, each with specific aromatic and aliphatic substitutions. Yet, the biological role of this conserved and specific lignin chemistry in each cell type remains unclear. Here, we investigated the roles of this lignin biochemical specificity for cellular functions by producing single cell analyses for three cell morphotypes of tracheary elements, which all allow sap conduction but differ in their morphology. We determined that specific lignin chemistries accumulate in each cell type. Moreover, lignin accumulated dynamically, increasing in quantity and changing in composition, to alter the cell wall biomechanics during cell maturation. For similar aromatic substitutions, residues with alcohol aliphatic functions increased stiffness whereas aldehydes increased flexibility of the cell wall. Modifying this lignin biochemical specificity and the sequence of its formation impaired the cell wall biomechanics of each morphotype and consequently hindered sap conduction and drought recovery. Together, our results demonstrate that each sap-conducting vascular cell type distinctly controls their lignin biochemistry to adjust their biomechanics and hydraulic properties to face developmental and environmental constraints.
ABSTRACT
Based on the previous synthesis of tetracyclic and tricyclic benzimidazoles starting from 1,4:3,6-dianhydro-d-fructose and o-phenylenediamines, a series of 5(6)-amino substituted tetracyclic and tricyclic benzimidazolequinones were obtained through the oxidation of 4,7-dimethoxy-benzimidazole analogues with bis(trifluoroacetoxy)iodobenzene (PIFA) and subsequent substitution with various aliphatic and aromatic amines. Biological evaluations of the target benzimidazolequinones indicated that all the arylamino-substituted benzimidazolequinones possess potent antitumour activity against human gastric cancer cells (MGC-803), especially compound a21-2. Furthermore, compound a21-2 inhibits gastric cancer cells proliferation and cell colony formation. Mechanistic investigations showed that compound a21-2 induces ROS production, which subsequently causes DNA damage and activation of ATM/Chk2, leading to G2/M phase arrest. ROS activates the c-Jun N-terminal kinase (JNK) pathway to induce mitochondrial-mediated apoptosis. In vivo studies showed that compound a21-2 inhibits the growth of tumours in nude mice without significant systemic toxicity. These findings suggest that compound a21-2 represents a promising candidate antitumour drug.
Subject(s)
Stomach Neoplasms , Animals , Apoptosis , Cell Line, Tumor , Cell Proliferation , Mice , Mice, Nude , Morpholines , Reactive Oxygen Species/metabolismABSTRACT
Atomic Force Microscope (AFM) probes were successfully functionalized with two types of nanocellulose, namely 2,2,6,6-tetramethylpiperidine-1-oxylradical (TEMPO)-mediated oxidized cellulose nanofibers (TOCNF) and cellulose nanocrystals (CNC) and used to study interfacial interactions of nanocellulose with Cu(II) ions and the Victoria blue B dye in liquid medium. TOCNF modified tip showed higher adhesion force due to adsorption of Cu(II) ions and dye molecules compared to CNC ones. Exploring the adsorption properties through classical reactive molecular dynamics simulations (ReaxFF) at the atomic scale confirmed that the Cu(II) ions promptly migrated and adsorbed onto the nanocelluloses through the co-operative chelating action of carboxyl and hydroxyl species. The adsorbed Cu(II) ions showed the tendency to self-organize by forming nano-clusters of variable size, whereas the dye adopted a flat orientation to maximize its adsorption. The satisfactory agreement between the two techniques suggests that functionalized AFM probes can be successfully used to study nanocellulose surface interactions in dry or aqueous environment.
ABSTRACT
The deposition of a thin layer of graphene oxide onto cellulose nanofibril membranes, to form CNF-GO layered-composite membranes, dramatically enhances their wet-mechanical stability, water flux and capacity to adsorb water pollutants (P. Liu, C. Zhu and A. P. Mathew, J. Hazard. Mater., 2019, 371, 484-493). In this work, we studied in real time the behavior of these layered membranes during filtration of water and metal ion solutions by means of in situ SAXS and reactive molecular dynamics (ReaxFF) computational simulations. SAXS confirms that the GO layers limit the swelling and structural deformations of CNFs during filtration of aqueous solutions. Moreover, during filtration of metal ion solutions, the connection of the CNF-GO network becomes highly complex mass-fractal like, with an increment in the correlation length. In addition, after ion adsorption, the SAXS data revealed apparent formation of nanoparticles during the drying stage and particle size increase as a function of time during drying. The molecular dynamics simulations, on the other hand, provide a deep insight into the assembly of both components, as well as elucidating the motion of the metal ions that potentially lead to the formation of metal clusters during adsorption, confirming the synergistic behavior of GO and CNFs for water purification applications.
ABSTRACT
Ultrathin graphene oxide (GO) layer was fabricated on cellulose nanofiber (CNF) membrane to achieve robust crosslinker free layered membrane with synergistic water flux and separation performance. Unlike pristine cellulosic or GO membranes, GO-CNF hybrid membranes exhibited significantly improved mechanical stability in both dry and wet states. All membranes showed negative surface zeta potential. GO: CNF membrane (1:100) exhibited significantly high water flux (18,123 ± 574 Lm-2 h-1 bar-1); higher than that of CNF membrane or the hydrophilic commercial reference membrane with comparable pore structure (Nylon 66, 0.2 µm). We hypothyse that a unique surface structure of "standing inserted GO nanosheets" observed at low concentrations of GO contributes enormously to its ultrafast water permeability through creation of numerous water transport nanochannels. The aniosptropic layered membranes exhibited >90% rejection of positively and negatively charged dyes through a combination of electrostatic interaction, hydrophobic interactions and molecular size exclusion. Construction of an ultrathin GO layer on CNF offers a unique and efficient way to prepare highly functional, economical and scalable water purification membranes having significant advantage with respect to flux, mechanical stability and rejection of dyes compared to isotropic membrane with GO nanosheets randomly dispersed in the cellulose nanofibrous network.
ABSTRACT
Ultrathin layers of 2,2,6,6-Tetramethyl-1-piperidinyloxy (TEMPO) Oxidized Cellulose Nanofibers (TOCNF) embedded with Graphene Oxide nanosheets (GOs) in different ratios were built, via the blade coating technique, on a polyvinylidene difluoride (PVDF) substrate to obtain superior membranes for separating water pollutants from aqueous media. Cellulose nanofiber-graphene oxide hybrid materials have shown a great potential for water purification due to their active microporous structure with extended areas rich in negatively charged carboxyl functional groups capable of adsorbing positively charged contaminants efficiently. In contrast to the pristine free-standing TOCNF films, which are completely impermeable, the ultrathin (68 nm thick) hybrid coating with a 100 : 1 TOCNF : GO ratio showed a stable water permeability (816 ± 3.4 L m-2 h-1 bar-1) higher than that of common polymeric membranes, and a very efficient size selectivity during filtration of water contaminated by various types of dyes. The membranes had high retention efficiency (82-99%) for dyes with hydrated radii greater than ≈0.5 nm due to the favorable combination of electrostatic/hydrophobic interactions with the hybrid matrices and steric entrapment controlled by the pore size. This was confirmed by theoretical calculations that revealed both the structure and dynamic behavior of the dyes in the complex environment of the membranes.
ABSTRACT
The self-assembly of nanocellulose and graphene oxide into highly porous biohybrid materials has inspired the design and synthesis of multifunctional membranes for removing water pollutants. The mechanisms of self-assembly, metal ion capture, and cluster formation on the biohybrids at the nano- and molecular scales are quite complex. Their elucidation requires evidence from the synergistic combination of experimental data and computational models. The AFM-based microscopy studies of (2,2,6,6-tetramethylpiperidine-1-oxylradical)-mediated oxidized cellulose nanofibers (TOCNFs), graphene oxide (GO), and their biohybrid membranes provide strong, direct evidence of self-assembly; small GO nanoparticles first attach and accumulate along a single TOCNF fiber, while the long, flexible TOCNF filaments wrap around the flat, wide GO planes, thus forming an amorphous and porous biohybrid network. The layered structure of the TOCNFs and GO membrane, derived from the self-assembly and its surface properties before and after the adsorption of Cu(II), is investigated by advanced microscopy techniques and is further clarified by the ReaxFF molecular dynamics (MD) simulations. The dynamics of the Cu(II)-ion capture by the TOCNF and GO membranes in solution and the ion cluster formation during drying are confirmed by the MD simulations. The results of this multidisciplinary investigation move the research one step forward by disclosing specific aspects of the self-assembly behavior of biospecies and suggesting effective design strategies to control the pore size and robust materials for industrial applications.
Subject(s)
Cellulose/chemistry , Copper/chemistry , Graphite/chemistry , Molecular Dynamics Simulation , Nanofibers/chemistry , Adsorption , Ions/chemistry , Microscopy, Atomic Force , Particle Size , Surface PropertiesABSTRACT
Nanocellulose, graphene oxide (GO), and their combinations there off have attracted great attention for the application of water purification recently because of their unique adsorption capacity, mechanical characteristics, coordination with transition metal ions, surface charge density, and so on. In the current study, (2,2,6,6-tetramethylpiperidine-1-oxylradical) (TEMPO)-mediated oxidized cellulose nanofibers (TOCNF) and GO sheets or graphene oxide nanocolloid (nanoGO) biohybrids were prepared by vacuum filtration method to obtain self-assembled adsorbents and membranes for water purification. The porous biohybrid structure, studied using advanced microscopy techniques, revealed a unique networking and self-assembling of TOCNF, GO, and nanoGO, driven by the morphology of the GO phase and stabilized by the intermolecular H-bonding between carboxyl groups and hydroxyl groups. The biohybrids exhibited a promising adsorption capacity toward Cu(II) due to TOCNF and formed a unique "arrested state" in water because of ionic cross-linking between adsorbed Cu(II) and the negatively charged TOCNF and GO phase. The mechanical performance of the freestanding biohybrid membranes investigated using PeakForce Quantative NanoMechanics characterization confirmed the enhanced modulus of the hybrid membrane compared to that of the TOCNF membrane. Besides, the TOCNF+nanoGO membrane shows unique hydrolytic stability and recyclability even under several cycles of adsorption and desorption and strong sonication. This study shows that TOCNF and nanoGO hybrids can generate new water-cleaning membranes with synergistic properties because of their high adsorption capacity, flexibility, hydrolytic stability, and mechanical robustness.
ABSTRACT
TEMPO (2,2,6,6-tetramethylpiperidine-1-oxylradical)-mediated oxidation nanofibers (TOCNF), as a biocompatible and bioactive material, have opened up a new application of nanocellulose for the removal of water contaminants. This development demands extremely sensitive and accurate methods to understand the surface interactions between water pollutants and TOCNF. In this report, we investigated the adsorption of metal ions on TOCNF surfaces using experimental techniques atthe nano and molecular scales with Cu(ii) as the target pollutant in both aqueous and dry forms. Imaging with in situ atomic force microscopy (AFM), together with a study of the physiochemical properties of TOCNF caused by adsorption with Cu(ii) in liquid, were conducted using the PeakForce Quantitative NanoMechanics (PF-QNM) mode at the nano scale. The average adhesion force between the tip and the target single TOCNF almost tripled after adsorption with Cu(ii) from 50 pN to 140 pN. The stiffness of the TOCNF was also enhanced because the Cu(ii) bound to the carboxylate groups and hardened the fiber. AFM topography, scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDS) mapping and X-ray photoelectron spectroscopy (XPS) indicated that the TOCNF were covered by copper nanolayers and/or nanoparticles after adsorption. The changes in the molecular structure caused by the adsorption were demonstrated by Raman and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). This methodology will be of great assistance to gain qualitative and quantitative information on the adsorption process and interaction between charged entities in aqueous medium.
ABSTRACT
The aim of this study was to develop a fundamental understanding of the adsorption behavior of metal ions on cellulose surfaces using experimental techniques supported by computational modeling, taking Ag(I) as an example. Force interactions among three types of cellulose microspheres (native cellulose and its derivatives with sulfate and phosphate groups) and the silica surface in AgNO3 solution were studied with atomic force microscopy (AFM) using the colloidal probe technique. The adhesion force between phosphate cellulose microspheres (PCM) and the silica surface in the aqueous AgNO3 medium increased significantly with increasing pH while the adhesion force slightly decreased for sulfate cellulose microspheres (SCM), and no clear adhesion force was observed for native cellulose microspheres (CM). The stronger adhesion enhancement for the PCM system is mainly attributed to the electrostatic attraction between Ag(I) and the negative silica surface. The observed force trends were in good agreement with the measured zeta potentials. The scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) analyses confirmed the presence of silver on the surface of cellulose microspheres after adsorption. This study showed that PCM with a high content of phosphate groups exhibited a larger amount of adsorbed Ag(I) than CM and SCM and possible clustering of Ag(I) to nanoparticles. The presence of the phosphate group and a wavenumber shift of the P-OH vibration caused by the adsorption of silver ions on the phosphate groups were further confirmed with computational studies using density functional theory (DFT), which gives support to the above findings regarding the adsorption and clustering of Ag(I) on the cellulose surface decorated with phosphate groups as well as IR spectra.