The Effect of Composition on the Properties and Application of CuO-NiO Nanocomposites Synthesized Using a Saponin-Green/Microwave-Assisted Hydrothermal Method.

In this study, we explored the formation of CuO nanoparticles, NiO nanoflakes, and CuO-NiO nanocomposites using saponin extract and a microwave-assisted hydrothermal method. Five green synthetic samples were prepared using aqueous saponin extract and a microwave-assisted hydrothermal procedure at 200 °C for 30 min. The samples were pristine copper oxide (100C), 75% copper oxide-25% nickel oxide (75C25N), 50% copper oxide-50% nickel oxide (50C50N), 25% copper oxide-75% nickel oxide (25C75N), and pristine nickel oxide (100N). The samples were characterized using FT-IR, XRD, XPS, SEM, and TEM. The XRD results showed that copper oxide and nickel oxide formed monoclinic and cubic phases, respectively. The morphology of the samples was useful and consisted of copper oxide nanoparticles and nickel oxide nanoflakes. XPS confirmed the +2 oxidation state of both the copper and nickel ions. Moreover, the optical bandgaps of copper oxide and nickel oxide were determined to be in the range of 1.29-1.6 eV and 3.36-3.63 eV, respectively, and the magnetic property studies showed that the synthesized samples exhibited ferromagnetic and superparamagnetic properties. In addition, the catalytic activity was tested against para-nitrophenol, demonstrating that the catalyst efficiency gradually improved in the presence of CuO. The highest rate constants were obtained for the 100C and 75C25N samples, with catalytic efficiencies of 98.7% and 78.2%, respectively, after 45 min.

Effect of Synthesis Conditions on CuO-NiO Nanocomposites Synthesized via Saponin-Green/Microwave Assisted-Hydrothermal Method.

This work presents the synthesis of CuO-NiO nanocomposites under different synthesis conditions. Nanocomposites were synthesized by merging a green synthesis process with a microwave-assisted hydrothermal method. The synthesis conditions were as follows: concentration of the metal precursors (0.05, 0.1, and 0.2 M), pH (9, 10, and 11), synthesis temperature (150 °C, 200 °C, and 250 °C), microwave treatment time (15, 30, and 45 min), and extract concentration (20 and 40 mL of 1 g saponin/10 mL water, and 30 mL of 2 g saponin/10 mL water). The phases and crystallite sizes of the calcined nanocomposites were characterized using XRD and band gap via UV-Vis spectroscopy, and their morphologies were investigated using SEM and TEM. The XRD results confirmed the formation of a face-centered cubic phase for nickel oxide, while copper oxide has a monoclinic phase. The calculated crystallite size was in the range of 29-39 nm. The direct band gaps of the samples prepared in this work were in the range of 2.39-3.17 eV.

Development of superior antibodies against the S-protein of SARS-Cov-2 using macrocyclic epitopes.

One of the proven methods to prevent and inhibit viral infections is to use antibodies to block the initial Receptor Binding Domain (RBD) of SARS-CoV-2 S protein and avoid its binding with the host cells. Thus, developing these RBD-targeting antibodies would be a promising approach for treating the SARS-CoV-2 infectious disease and stop virus replication. Macrocyclic epitopes constitute closer mimics of the receptor's actual topology and, as such, are expected to be superior epitopes for antibody generation. This work demonstrated the vital effect of the three-dimensional shape of epitopes on the developed antibodies' activity against RBD protein of SARS-CoV-2. The molecular dynamics studies showed the greater stability of the cyclic epitopes in comparison with the linear counterpart, which was reflected in the activity of their produced antibodies. Indeed, the antibodies we developed using macrocyclic epitopes showed superiority with respect to binding to RBD proteins compared to antibodies formed from a linear peptide. The results of the present work constitute a roadmap for developing superior antibodies that could be used to inhibit the activity of the SARS-CoV-2 and prevent its reproduction.

Structure-Based Epitope Design: Toward a Greater Antibody-SARS-CoV-2 RBD Affinity.

Efficient COVID-19 vaccines are widely acknowledged as the best way to end the global pandemic. SARS-CoV-2 receptor-binding domain (RBD) plays fundamental roles related to cell infection. Antibodies could be developed to target RBD and represent a potential approach for the neutralization of the virus. Epitopes used to produce antibodies are generally linear peptides and thus possess multiple confirmations that do not reflect the actual topology of the targeted part in the native protein. On the other hand, macrocyclic epitopes could constitute closer mimics of the native protein topology and, as such, could generate superior antibodies. In this study, we demonstrated the vital effect of the size and the three-dimensional shape of epitopes on the activity of the developed antibodies against the RBD of SARS-CoV-2. The molecular dynamics studies showed the greater stability of the cyclic epitopes compared with the linear counterparts, which was reflected in the affinity of the produced antibodies. The antibodies developed using macrocyclic epitopes showed superiority with respect to binding to RBD compared to antibodies formed from linear peptides. This study constitutes a roadmap for developing superior antibodies that could be used to inhibit the activity of SARS-CoV-2.

SARS-CoV-2 Receptor Binding Domain as a Stable-Potential Target for SARS-CoV-2 Detection by Surface-Enhanced Raman Spectroscopy.

In this work, we report a new approach for detecting SARS-CoV-2 RBD protein (RBD) using the surface-enhanced Raman spectroscopy (SERS) technique. The optical enhancement was obtained thanks to the preparation of nanostructured Ag/Au substrates. Fabricated Au/Ag nanostructures were used in the SERS experiment for RBD protein detection. SERS substrates show higher capabilities and sensitivity to detect RBD protein in a short time (3 s) and with very low power. We were able to push the detection limit of proteins to a single protein detection level of 1 pM. The latter is equivalent to 1 fM as a detection limit of viruses. Additionally, we have shown that the SERS technique was useful to figure out the presence of RBD protein on antibody functionalized substrates. In this case, the SERS detection was based on protein-antibody recognition, which led to shifts in the Raman peaks and allowed signal discrimination between RBD and other targets such as Bovine serum albumin (BSA) protein. A perfect agreement between a 3D simulated model based on finite element method and experiment was reported confirming the SERS frequency shift potential for trace proteins detection. Our results could open the way to develop a new prototype based on SERS sensitivity and selectivity for rapid detection at a very low concentration of virus and even at a single protein level.

In vivo oral insulin delivery via covalent organic frameworks.

With diabetes being the 7th leading cause of death worldwide, overcoming issues limiting the oral administration of insulin is of global significance. The development of imine-linked-covalent organic framework (nCOF) nanoparticles for oral insulin delivery to overcome these delivery barriers is herein reported. A gastro-resistant nCOF was prepared from layered nanosheets with insulin loaded between the nanosheet layers. The insulin-loaded nCOF exhibited insulin protection in digestive fluids in vitro as well as glucose-responsive release, and this hyperglycemia-induced release was confirmed in vivo in diabetic rats without noticeable toxic effects. This is strong evidence that nCOF-based oral insulin delivery systems could replace traditional subcutaneous injections easing insulin therapy.

Effect of pH and Nanoparticle Capping Agents on Cr (III) Monitoring in Water: A Kinetic Way to Control the Parameters of Ultrasensitive Environmental Detectors.

In this work, we apply surface-enhanced Raman spectroscopy (SERS) to study the kinetics of chromium Cr (III) detection in solution using EDTA and silver nanoparticles (AgNPs). We examine for the first time the effect of pH and nanoparticles' capping agent on the kinetic mechanism of Cr (III) detection using SERS temporal variations. The full width at half maximum (FWHM) and Raman shift variations show that the mechanism of detection is composed of two steps: a first one consisting of chemical coordination between Cr (III) and AgNPs that leads to exalted chemical and electromagnetic enhancement and the second one is an aggregation process with an important optical enhancement. The obtained results showed that the first step in the detection at lower pH was five times faster than in a basic medium using citrate capped silver nanoparticles (Cit-AgNPs). On the other hand, using a capping agent with dicarboxylate groups such as oxalate (Oxa-AgNPs) led to an important enhancement in SERS detection signal (more than 30 times) compared with Cit-AgNPs, although the detection kinetic's mechanism was slower.

Toward the Development of Ultrasensitive Detectors for Environmental Applications: A Kinetic Study of Cr(III) Monitoring in Water Using EDTA and SERS Techniques.

We report for the first time kinetic studies on chromium(III) detection in aqueous solution using citrate-capped silver nanoparticles (AgNPs) and the surface-enhanced Raman spectroscopy (SERS) technique. Moreover, we have shown an important effect of adding ethylenediaminetetraacetic acid (EDTA) on the enhancement and the stability of the Raman signal. The origin of the SERS signal was attributed to the coordination of Cr(III) by citrate/EDTA molecules and the formation of hot spots on aggregated AgNPs. Depending on the mixing method of Cr(III) and EDTA with AgNPs, the temporal SERS spectral features reveal a Prout-Tompkins or a Langmuir kinetic detection model. The UV-visible data, the temporal response of the Raman signal, and the scanning electron microscopy analysis have allowed us to elucidate the mechanism of Cr(III) detection. We observed that mixing simultaneously Cr(III), AgNPs, and EDTA leads to the most stable and intense time-dependent SERS signal. The obtained results should open the way to perform kinetic studies on different host-guest interactions in solution using the SERS technique.

Covalent Organic Framework Embedded with Magnetic Nanoparticles for MRI and Chemo-Thermotherapy.

Nanoscale imine-linked covalent organic frameworks (nCOFs) were first loaded with the anticancer drug Doxorubicin (Dox), coated with magnetic iron oxide nanoparticles (γ-Fe2O3 NPs), and stabilized with a shell of poly(l-lysine) cationic polymer (PLL) for simultaneous synergistic thermo-chemotherapy treatment and MRI imaging. The pH responsivity of the resulting nanoagents (γ-SD/PLL) allowed the release of the drug selectively within the acidic microenvironment of late endosomes and lysosomes of cancer cells (pH 5.4) and not in physiological conditions (pH 7.4). γ-SD/PLL could efficiently generate high heat (48 °C) upon exposure to an alternating magnetic field due to the nCOF porous structure that facilitates the heat conduction, making γ-SD/PLL excellent heat mediators in an aqueous solution. The drug-loaded magnetic nCOF composites were cytotoxic due to the synergistic toxicity of Dox and the effects of hyperthermia in vitro on glioblastoma U251-MG cells and in vivo on zebrafish embryos, but they were not significantly toxic to noncancerous cells (HEK293). To the best of our knowledge, this is the first report of multimodal MRI probe and chemo-thermotherapeutic magnetic nCOF composites.

Aqueous Synthesis of Triphenylphosphine-Modified Gold Nanoparticles for Synergistic In Vitro and In Vivo Photothermal Chemotherapy.

Triphenylphosphine (TPP) surface-functionalized and F-108 Pluronic-stabilized gold nanoparticles (F-108@TPP-AuNPs) have been synthesized through a one-step approach, leading to well-defined (9.6±1.6 nm) and water-soluble nanoparticles by microwave heating an aqueous solution of TPP-AuI Cl in the presence of a Pluronic polymer under basic conditions. TPP release was negligible under physiological conditions, but enhanced significantly at an acidic pH (5.4) mimicking that of a cancer cell. Laser irradiation (532 nm) raised the temperature of an aqueous solution of F-108@TPP-AuNPs to 51.7 °C within 5 min, confirming efficient light-to-heat conversion capabilities without significant photodegradation. TEM confirmed intracellular localization of F-108@TPP-AuNPs in the cytosol, endosomes and lysosomes of HeLa cells. F-108@TPP-AuNPs were well tolerated by HeLa cells and zebrafish embryos at ambient temperatures and became toxic upon heat activation, suggesting synergistic interactions between heat and cytotoxic action by TPP.

Thioether-Crown-Rich Calix[4]arene Porous Polymer for Highly Efficient Removal of Mercury from Water.

A rational design of adsorbents with high uptake efficiency and fast kinetics for highly toxic pollutants is a key challenge in environmental remediation. Here, we report the design of a well-defined thioether-crown-rich porous calix[4]arene-based mesoporous polymer S-CX4P and its utility in removal of highly relevant toxic mercury (Hg2+) from water. The polymer shows an exceptional, record-high uptake efficiency of 1686 mg g-1 and the fastest initial adsorption rate of 278 mg g-1 min-1. Remarkably, S-CX4P can effectively remove Hg2+ from high concentration (5 ppm) to below the acceptable limit for drinking water (2 ppb) even in the presence of other competitive metals at high concentrations. In addition, the polymer can be easily regenerated at room temperature and reused multiple times with negligible loss in uptake rate and efficiency. The results demonstrate the potential of rationally designed thioether-crown-rich polymers for high performance mercury removal.

Redox-Responsive Covalent Organic Nanosheets from Viologens and Calix[4]arene for Iodine and Toxic Dye Capture.

Owing to their chemical and thermal stabilities, high uptake capacities, and easy recyclability, covalent organic polymers (COPs) have shown promise as pollutant sponges. Herein, we describe the use of diazo coupling to synthesize two cationic COPs, COP1++ and COP2++ , that incorporate a viologen-based molecular switch and an organic macrocycle, calix[4]arene. The COPs form nanosheets that have height profiles of 6.00 nm and 8.00 nm, respectively, based on AFM measurements. The sheets remain morphologically intact upon one- or two-electron reductions of their viologen subunits. MD simulations of the COPs containing dicationic viologens indicate that the calix[4]arenes adopt a partial cone conformation and that, in height, the individual 2D polymer layers are 5.48 Šin COP1++ and 5.65 Šin COP2++ , which, together with the AFM measurements, suggests that the nanosheets are composed of 11 and 14 layers, respectively. Whether their viologens are in dicationic, radical cationic, or neutral form, the COPs exhibit high affinity for iodine, reaching up to 200 % mass increase when exposed to iodine vapor at 70 °C, which makes the materials among the best-performing nanosheets for iodine capture reported in the literature. In addition, the COPs effectively remove Congo red from solution in the pH range of 2-10, reaching nearly 100 % removal within 15 minutes at acidic pH.

Palladium-Loaded Cucurbit[7]uril-Modified Iron Oxide Nanoparticles for C-C Cross-Coupling Reactions.

Cucurbit[7]uril modified iron oxide nanoparticles (CB[7]NPs) were loaded with palladium to form nano-catalysts (Pd@CB[7]NPs) that, with microwave heating, catalysed Suzuki-Miyaura, Sonogashira, and Mizoroki-Heck cross-coupling reactions. Reactions were run in environmentally benign 1:1 ethanol/water solvent under convenient aerobic conditions. In a preliminary screening, conversions and yields were uniformly high with turn over frequencies (TOF) ranging from 64 to 7360 h-1 . The nano-catalysts could be recovered with a magnet and reused several times (6 times for Suzuki-Miayura reaction) without loss of activity.

Sequential Delivery of Doxorubicin and Zoledronic Acid to Breast Cancer Cells by CB[7]-Modified Iron Oxide Nanoparticles.

Drug-loaded magnetic nanoparticles were synthesized and used for the sequential delivery of the antiresorptive agent zoledronic acid (Zol) and the cytotoxic drug doxorubicin (Dox) to breast cancer cells (MCF-7). Zol was attached to bare iron oxide nanoparticles (IONPs) via phosphonate coordination to form Z-NPs. The unbound imidazole of Zol was then used to complex the organic macrocycle CB[7] to obtain CZ-NPs. Dox was complexed to the CZ-NPs to form the fully loaded particles (DCZ-NPs), which were stable in solution at 37 °C and physiological pH (7.4). Fluorescence spectroscopy established that Dox is released in solution from DCZ-NPs suddenly (i) when the particles are subjected to magnetically induced heating to 42 °C at low pH (5.0) and (ii) in the presence of glutathione (GSH). Mass spectrometry indicated that Zol is released slowly in solution at low pH after Dox release. Magnetic measurements with a magnetic reader revealed that DCZ-NPs are internalized preferentially by MCF-7 cells versus nonmalignant cells (HEK293). Zol and Dox acted synergistically when delivered by the particles. DCZ-NPs caused a decrease in the viability of MCF-7 cells that was greater than the net decrease caused when the drugs were added to the cells individually at concentrations equivalent to those delivered by the particles. MCF-7 cells were treated with DCZ-NPs and subjected to an alternating magnetic field (AMF) which, with the nanoparticles present, raised the temperature of the cells and triggered the intracellular release of Dox, as indicated by fluorescence activated cell sorting (FACS). The cytotoxic effects of the DCZ-NPs on MCF-7 cells were enhanced 10-fold by AMF-induced heating. DCZ-NPs were also able to completely inhibit MCF-7 cell adhesion and invasion in vitro, indicating the potential of the particles to act as antimetastatic agents. Together these results demonstrate that DCZ-NPs warrant development as a system for combined chemo- and thermo-therapeutic treatment of cancer.

Macrocyclic cell penetrating peptides: a study of structure-penetration properties.

Arginine-rich cell penetrating peptides are short cationic peptides able to cross biological membranes despite their peptidic character. In order to optimize their penetration properties and further elucidate their mechanisms of cellular entry, these peptides have been intensively studied for the last two decades. Although several parameters are simultaneously involved in the internalization mechanism, recent studies suggest that structural modifications influence cellular internalization. Particularly, backbone rigidification, including macrocyclization, was found to enhance proteolytic stability and cellular uptake. In the present work, we describe the synthesis of macrocyclic arginine-rich cell penetrating peptides and study their cellular uptake properties using a combination of flow cytometry and confocal microscopy. By varying ring size, site of cyclization, and stereochemistry of the arginine residues, we studied their structure-uptake relationship and showed that the mode and site of cyclization as well as the stereochemistry influence cellular uptake. This study led to the identification of a hepta-arginine macrocycle as efficient as its linear nona-arginine congener to enter cells.

Multiple hydrogen bond interactions in the processing of functionalized multi-walled carbon nanotubes.

In a set of unprecedented experiments combining "bottom-up" and "top-down" approaches, we report the engineering of patterned surfaces in which functionalized MWCNTs have been selectively adsorbed on polymeric matrices as obtained by microlithographic photo-cross-linking of polystyrene polymers bearing 2,6-di(acetylamino)-4-pyridyl moieties (PS1) deposited on glass or Si. All patterned surfaces have been characterized by optical, fluorescence, and SEM imaging techniques, showing the local confinement of the CNTs materials on the polymeric microgrids. These results open new possibilities toward the controlled manipulation of CNTs on surfaces, using H-bonding self-assembly as the main driving force.

Modular engineering of H-bonded supramolecular polymers for reversible functionalization of carbon nanotubes.

A H-bond-driven, noncovalent, reversible solubilization/functionalization of multiwalled carbon nanotubes (MWCNTs) in apolar organic solvents (CHCl(3), CH(2)Cl(2), and toluene) has been accomplished through a dynamic combination of self-assembly and self-organization processes leading to the formation of supramolecular polymers, which enfold around the outer wall of the MWCNTs. To this end, a library of phenylacetylene molecular scaffolds with complementary recognition sites at their extremities has been synthesized. They exhibit triple parallel H-bonds between the NH-N-NH (DAD) functions of 2,6-di(acetylamino)pyridine and the CO-NH-CO (ADA) imidic groups of uracil derivatives. These residues are placed at 180° relative to each other (linear systems) or at 60°/120° (angular modules), in order to tune their ability of wrapping around MWCNTs. Molecular Dynamics (MD) simulations showed that the formation of the hybrid assembly MWCNT•[X•Y](n) (where X = 1a or 1b -DAD- and Y = 2, 3, or 4 -ADA-) is attributed to π-π and CH-π interactions between the graphitic walls of the carbon materials and the oligophenyleneethynylene polymer backbones along with its alkyl groups, respectively. Addition of polar or protic solvents, such as DMSO or MeOH, causes the disruption of the H-bonds with partial detachment of the polymer from the CNTs, followed by precipitation. Taking advantage of the chromophoric and luminescence properties of the molecular subunits, the solubilization/precipitation processes have been monitored by UV-vis absorption and luminescence spectroscopies. All hybrid MWCNTs-polymer materials have been also structurally characterized via thermogravimetric analysis (TGA), transmission electron microscopy (TEM), atomic force microscopy (AFM), scanning tunneling microscopy (STM), and X-ray photoelectron spectroscopy (XPS).

Electrostatically-driven assembly of MWCNTs with a europium complex.

Luminescent carbon-based materials have been prepared by electrostatic self-assembly of negatively-charged luminescent Eu(III)-complex with imidazolium-functionalized MWCNTs.