Design, Synthesis, Anti-Inflammatory Activity, DFT Modeling and Docking Study of New Ibuprofen Derivatives.

A new ibuprofen derivative, (E)-2-(4-isobutylphenyl)-N'-(4-oxopentan-2-ylidene) propane hydrazide (IA), was synthesized, along with its metal complexes with Co, Cu, Ni, Gd, and Sm, to investigate their anti-inflammatory efficacy and COX-2 inhibition potential. Comprehensive characterization, including 1H NMR, MS, FTIR, UV-vis spectroscopy, and DFT analysis, were employed to determine the structural configurations, revealing unique motifs for Gd/Sm (capped square antiprismatic/tricapped trigonal prismatic) and Cu/Ni/Co (octahedral) complexes. Molecular docking with the COX-2 enzyme (PDB code: 5IKT) and pharmacokinetic assessments through SwissADME indicated that these compounds have superior binding energies and pharmacokinetic profiles, including BBB permeability and gastrointestinal absorption, compared to the traditional ibuprofen standalone. Their significantly lower IC50 values further suggest a higher efficacy as anti-inflammatory agents and COX-2 inhibitors. These research findings not only introduce promising ibuprofen derivatives for therapeutic applications but also set the stage for future validation and exploration of this new generation of ibuprofen compounds.

Alginate-based hydrogel platform embedding silver nanoparticles and cisplatin: characterization of the synergistic effect on a breast cancer cell line.

Introduction: Breast cancer is a significant cause of mortality in women globally, and current treatment approaches face challenges due to side effects and drug resistance. Nanotechnology offers promising solutions by enabling targeted drug delivery and minimizing toxicity to normal tissues. Methods: In this study, we developed a composite platform called (Alg-AgNPs-CisPt), consisting of silver nanoparticles coated with an alginate hydrogel embedding cisplatin. We examined the effectiveness of this nanocomplex in induce synergistic cytotoxic effects on breast cancer cells. Results and Discussion: Characterization using various analytical techniques confirmed the composition of the nanocomplex and the distribution of its components. Cytotoxicity assays and apoptosis analysis demonstrated that the nanocomplex exhibited greater efficacy against breast cancer cells compared to AgNPs or cisplatin as standalone treatments. Moreover, the nanocomplex was found to enhance intracellular reactive oxygen species levels, further validating its efficacy. The synergistic action of the nanocomplex constituents offers potential advantages in reducing side effects associated with higher doses of cisplatin as a standalone treatment. Overall, this study highlights the potential of the (Alg-AgNPs-CisPt) nanocomplex as a promising platform embedding components with synergistic action against breast cancer cells.

Terbium Removal from Aqueous Solutions Using a In2O3 Nanoadsorbent and Arthrospira platensis Biomass.

Terbium is a rare-earth element with critical importance for industry. Two adsorbents of different origin, In2O3 nanoparticles and the biological sorbent Arthrospira platensis, were applied for terbium removal from aqueous solutions. Several analytical techniques, including X-ray diffraction, Fourier-transform infrared spectroscopy, and scanning electron microscopy, were employed to characterize the adsorbents. The effect of time, pH, and terbium concentration on the adsorption efficiency was evaluated. For both adsorbents, adsorption efficiency was shown to be dependent on the time of interaction and the pH of the solution. Maximum removal of terbium by Arthrospira platensis was attained at pH 3.0 and by In2O3 at pH 4.0-7.0, both after 3 min of interaction. Several equilibrium (Langmuir, Freundlich, and Temkin) and kinetics (pseudo-first order, pseudo-second order, and Elovich) models were applied to describe the adsorption. The maximum adsorption capacity was calculated from the Langmuir model as 212 mg/g for Arthrospira platensis and 94.7 mg/g for the In2O3 nanoadsorbent. The studied adsorbents can be regarded as potential candidates for terbium recovery from wastewater.

Efficient Dual-Function Catalyst: Palladium-Copper Nanoparticles Immobilized on Co-Cr LDH for Seamless Aerobic Oxidation of Benzyl Alcohol and Nitrobenzene Reduction.

Layered double hydroxides (LDHs) present exciting possibilities across various industries, ranging from catalytic applications to water remediation. By immobilizing nanoparticles, LDHs' characteristics and functionality can be enhanced, allowing for synergetic interactions that further expand their potential uses. A simple chemical method was developed to produce well-dispersed Pd-Cu NPs on a Co-Cr LDH support using a combination of in situ coprecipitation/hydrothermal and sol-immobilization techniques. The Pd-Cu@Co-Cr LDH catalysts was obtained, showing its catalytic activity in promoting the aerobic oxidation of alcohols and enabling the reduction of nitro-compounds through NaBH4 mediation. The physicochemical properties of the prepared catalyst were comprehensively investigated utilizing a range of analytical techniques, comprising FTIR, XRD, XPS, TGA, nitrogen adsorption isotherm, FESEM, and HRTEM-EDX. The findings showed the significance of immobilizing the bimetallic Pd-Cu nanoparticles on the Co-Cr LDH via an exceptional performance in the aerobic oxidation of benzyl alcohol (16% conversion, 99.9% selectivity to benzaldehyde) and the reduction of nitrobenzene (98.2% conversion, rate constant of 0.0921 min-1). The improved catalytic efficacy in benzyl alcohol oxidation and nitrobenzene reduction on the Pd-Cu@Co-Cr LDH catalyst is attributed to the uniform distribution and small size of the Pd-Cu NPs as active sites on the Co-Cr LDH surface. The prepared catalyst demonstrated exceptional stability during repeated runs. This study paves the way for multiple opportunities in tailoring, producing, and precisely controlling catalysts for various organic transformation reactions.

Efficient nitrophenol reduction with Noria-GO nanocomposite decorated with Pd-Cu nanoparticles.

We report a facile approach to synthesize Pd-Cu nanoparticles immobilized on a Noria-GO nanocomposite for efficient nitrophenol reduction. The unique architecture of the Noria and the hydrophilic nature of GO contribute to the improved performance and structure of the resulting nanocomposite. The simple sol-immobilization approach employed NaBH4 as a reductant and polyvinyl alcohol as a capping agent to evenly decorate small Pd-Cu nanoparticles with a diameter of 1.4 nm on the Noria-GO surface. The prepared Pd-Cu@Noria-GO nanocomposite was utilized as a nanocatalyst in converting of nitrophenol to aminophenol using NaBH4 solution. Our Pd-Cu@Noria-GO nanocomposite exhibited superior catalytic efficacy with large conversion percentages, Kapp, and KAF values of 95%, 0.225 min-1, and 225 min-1g-1, respectively. X-ray photoemission spectroscopy confirmed the oxidation state of the prepared nanoparticles, and TEM findings demonstrated the homogenous decoration of Pd-Cu NPs on the Noria-GO surface. Additionally, the durability of the Pd-Cu@Noria-GO nanocomposite shown its potential as a robust and promising material for remediating organic contaminants. Our results indicate that Pd-Cu@Noria-GO nanocomposite can be an effective and sustainable approach for mitigating the hazards associated with nitrophenols.

Microspheres with 2D rGO/Alginate Matrix for Unusual Prolonged Release of Cefotaxime.

A synergistic interaction between reduced graphene oxide (rGO) and a biodegradable natural polymer, sodium alginate, was developed to create unique microspheres with protruding spiky features at the surface (spiky microspheres) that act as a super encapsulation and sustained release system for the highly effective antibiotic cefotaxime. Three forms of microspheres, namely alginate (Alg), alginate-cefotaxime (Alg-CTX), and alginate-cefotaxime-reduced graphene (Alg-CTX-rGO) composites, were prepared using calcium chloride as a cross-linking agent. The microspheres were characterized using field emission scanning electron microscopy (FESEM), Fourier-transform infrared (FT-IR) spectroscopy, and X-ray diffraction to investigate their pores, roughness, surface morphology, functional groups, phase formation, purity, and structural properties. The membrane diffusion method was employed to determine the release profile of Cefotaxime from the fabricated microspheres. The antibacterial activities of CTX solution, Alg microspheres, Alg-CTX microspheres, and Alg-CTX-rGO microspheres were investigated against gram-negative bacteria (Escherichia coli) using the agar diffusion method on Muller-Hinton agar. The prepared samples exhibited excellent results, suggesting their potential for enhanced antibiotic delivery. The results demonstrated the potential of the microsphere 2D rGO/alginate matrix for enhancing cefotaxime delivery with an unusual, prolonged release profile.

Inducible Nitric Oxide Synthase Embedded in Alginate/Polyethyleneimine Hydrogel as a New Platform to Explore NO-Driven Modulation of Biological Function.

Nitric oxide (NO), a small free radical molecule, turned out to be pervasive in biology and was shown to have a substantial influence on a range of biological activities, including cell growth and apoptosis. This molecule is involved in signaling and affects a number of physiologic functions. In recent decades, several processes related to cancer, such as angiogenesis, programmed cell death, infiltration, cell cycle progression, and metastasis, have been linked with nitric oxide. In addition, other parallel work showed that NO also has the potential to operate as an anti-cancer agent. As a result, it has gained attention in cancer-related therapeutics. The nitric oxide synthase enzyme family (NOS) is required for the biosynthesis of nitric oxide. It is becoming increasingly popular to develop NO-releasing materials as strong tumoricidal therapies that can deliver sustained high concentrations of nitric oxide to tumor sites. In this paper, we developed NO-releasing materials based on sodium alginate hydrogel. In this regard, alginate hydrogel discs were modified by adsorbing layers of polyethyleneimine and iNOS-oxygenase. These NO-releasing hydrogel discs were prepared using the layer-by-layer film building technique. The iNOS-oxygenase is adsorbed on the positively charged polyethyleneimine (PEI) matrix layer, which was formed on a negatively charged sodium alginate hydrogel. We show that nitric oxide is produced by enzymes contained within the hydrogel material when it is exposed to a solution containing all the components necessary for the NOS reaction. The electrostatic chemical adsorption of the layer-by-layer process was confirmed by FTIR measurements as well as scanning electron microscopy. We then tested the biocompatibility of the resulting modified sodium alginate hydrogel discs. We showed that this NOS-PEI-modified hydrogel is overall compatible with cell growth. We characterized the NOS/hydrogel films and examined their functional features in terms of NO release profiles. However, during the first 24 h of activity, these films show an increase in NO release flux, followed by a gradual drop and then a period of stable NO release. These findings show the inherent potential of using this system as a platform for NO-driven modulation of biological functions, including carcinogenesis.

Rapid Detection of Recurrent Non-Muscle Invasive Bladder Cancer in Urine Using ATR-FTIR Technology.

Non-muscle Invasive Bladder Cancer (NMIBC) accounts for 80% of all bladder cancers. Although it is mostly low-grade tumors, its high recurrence rate necessitates three-times-monthly follow-ups and cystoscopy examinations to detect and prevent its progression. A rapid liquid biopsy-based assay is needed to improve detection and reduce complications from invasive cystoscopy. Here, we present a rapid spectroscopic method to detect the recurrence of NMIBC in urine. Urine samples from previously-diagnosed NMIBC patients (n = 62) were collected during their follow-up visits before cystoscopy examination. Cystoscopy results were recorded (41 cancer-free and 21 recurrence) and attenuated total refraction Fourier transform infrared (ATR-FTIR) spectra were acquired from urine samples using direct application. Spectral processing and normalization were optimized using parameter grid searching. We assessed their technical variability through multivariate analysis and principal component analysis (PCA). We assessed 35 machine learning models on a training set (70%), and the performance was evaluated on a held-out test set (30%). A Regularized Random Forests (RRF) model achieved a 0.92 area under the receiver operating characteristic (AUROC) with 86% sensitivity and 77% specificity. In conclusion, our spectroscopic liquid biopsy approach provides a promising technique for the early identification of NMIBC with a less invasive examination.

A Novel Ibuprofen Derivative and Its Complexes: Physicochemical Characterization, DFT Modeling, Docking, In Vitro Anti-Inflammatory Studies, and DNA Interaction.

A novel derivative of ibuprofen and salicylaldehyde N'-(4-hydroxybenzylidene)-2-(4-isobutylphenyl) propane hydrazide (HL) was synthesized, followed by its complexation with Cu, Ni, Co, Gd, and Sm. The compounds obtained were characterized by 1HNMR, mass spectrometry, UV-Vis spectroscopy, FT-IR spectroscopy, thermal analysis (DTA and TGA), conductivity measurements, and magnetic susceptibility measurements. The results indicate that the complexes formed were [Cu(L)(H2O)]Cl·2H2O, [Ni(L)2], [Co(L)2]·H2O, [Gd(L)2(H2O)2](NO3)·2H2O and [Sm(L)2(H2O)2](NO3)·2H2O. The surface characteristics of the produced compounds were evaluated by DFT calculations using the MOE environment. The docking was performed against the COX2 targeting protein (PDB code: 5IKT Homo sapiens). The binding energies were -7.52, -9.41, -9.51, -8.09, -10.04, and -8.05 kcal/mol for HL and the Co, Ni, Cu, Sm, and Gd complexes, respectively, which suggests the enhancement of anti-inflammatory behaviors compared with the binding energy of ibuprofen (-5.38 kcal/mol). The anti-inflammatory properties of the new compounds were assessed in vitro using the western blot analysis method and the enzyme-linked immunosorbent assay (ELISA), consistent with the outcomes obtained from docking. The half-maximal inhibitory concentration (IC50) values are 4.9, 1.7, 3.7, 5.6, 2.9, and 2.3 µM for HL and the Co, Ni, Cu, Sm, and Gd complexes, respectively, showing that they are more effective inhibitors of COX2 than ibuprofen (IC50 = 31.4 µM). The brain or intestinal estimated permeation method (BOILED-Egg) showed that HL and its Co complex have high gastrointestinal absorption, while only the free ligand has high brain penetration. The binding constants of Co, Cu, and Gd complexes with DNA were recorded as 2.20 × 104, 2.27 × 106, and 4.46 × 103 M-1, respectively, indicating the intercalator behavior of interaction. The newly synthesized ibuprofen derivative and its metal complexes showed greater anti-inflammatory activity than ibuprofen.

Highly Efficient Photocatalysts for Methylene Blue Degradation Based on a Platform of Deposited GO-ZnO Nanoparticles on Polyurethane Foam.

The demand for reactive dyes in industries has increased rapidly in recent years, and producing a large quantity of dye-containing effluent waste contaminates soils and water streams. Current efforts to remove these harmful dyes have focused on utilizing functionalized nanomaterials. A 3D polyurethane foam loaded with reduced graphene oxide (rGO) and ZnO nanocomposite (PUF/rGO/ZnO) has been proposed as an efficient structural design for dye degradation under the influence of visible light. The proposed structure was synthesized using a hydrothermal route followed by microwave irradiation. The resultant 3D PUF/rGO/ZnO was examined and characterized by various techniques such as XRD, FTIR, SEM, EDAX, BET, and UV-visible spectroscopy. SEM data illustrated that a good dispersion and embedment of the rGO/ZnO NPs within the PUF matrix occurred. The adsorption capacity for neat PUF showed that around 20% of the Methylene blue (MB) dye was only adsorbed on its surface. However, it was found that an exceptional adsorption capacity for MB degradation was observed when the rGO/ZnO NPs inserted into the PUF, which initially deteriorated to ~ 70 % of its initial concentration. Notably, the MB dye was completely degraded within 3 h.

Fast and Reliable Synthesis of Melanin Nanoparticles with Fine-Tuned Metal Adsorption Capacities for Studying Heavy Metal Ions Uptake.

PURPOSE: Adsorption and uptake of heavy metals by polymeric nanoparticles is driven by a variety of physicochemical processes. In this work, we examined heavy metal uptake by synthetic melanin nanoparticles and analyzed physicochemical properties that affect the extent of metal uptake by the nanoparticles. METHODS: Eumelanin nanoparticles were synthesized in a one-pot fast process from a 5,6-diacetoxy indole precursor that is hydrolyzed in situ into dihydroxy indole (DHI). The method allows the possibility of changing the level of sodium ions that ends up in the nanoparticles. Two variants of synthetic DHI-melanin (low-sodium and high sodium variants) were evaluated and demonstrated different relative adsorption efficiencies for heavy metal cations. RESULTS AND DISCUSSION: For the low-sodium DHI-melanin and in terms of percentages of metal ion removal, the relative order of extraction from 50 ppm solutions was Zn2+ > Cd2+ > Ni2+ > Co2+ > Cu2+ > Pb2+, with the extraction percentages ranging from 90% down to 76%, for a 30-minute adsorption time before equilibrium. The lower-sodium DHI-melanin consistently removed more Zn2+ than the higher-sodium variant. Electron microscopy (SEM) showed an increase in melanin particle size after metal ions uptake. In addition, X-ray photoelectron spectroscopy (XPS) of DHI-melanin particles with depth profiling after Zn ions uptake supported particle swelling and ion transport within the particles. CONCLUSION: These initial studies showed the potential of this straightforward synthesis to obtain synthetic DHI-melanin nanoparticles similar to those from biological sources with the possibility to fine-tune their metal adsorption capacity. These synthetic nanoparticles can be used either for the removal of a variety of metal ions or to mimic and study mechanisms of metal uptake by melanin deriving from biological sources, with the potential to understand, for instance, differential heavy metal uptake by various melanic pigments.

Synthetic melanin nanoparticles as peroxynitrite scavengers, photothermal anticancer and heavy metals removal platforms.

Melanin is a ubiquitous natural polyphenolic pigment with versatile applications including physiological functions. This polymeric material is found in a diversity of living organisms from bacteria to mammals. The biocompatibility and thermal stability of melanin nanoparticles make them good candidates to work as free radical scavengers and photothermal anticancer substrates. Research studies have identified melanin as an antioxidative therapeutic agent and/or reactive oxygen species (ROS) scavenger that includes neutralization of peroxynitrite. In addition, melanin nanoparticles have emerged as an anticancer photothermal platform that has the capability to kill cancer cells. Recently, melanin nanoparticles have been successfully used as chelating agents to purify water from heavy metals, such as hexavalent chromium. This review article highlights some selected aspects of cutting-edge melanin applications. Herein, we will refer to the recent literature that addresses melanin nanoparticles and its useful physicochemical properties as a hot topic in biomaterial science. It is expected that the techniques of Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), and time-resolved Electron Paramagnetic Resonance (EPR) will have a strong impact on the full characterization of melanin nanoparticles and the subsequent exploration of their physiological and chemical mechanisms.

Functional Layer-by-Layer Thin Films of Inducible Nitric Oxide (NO) Synthase Oxygenase and Polyethylenimine: Modulation of Enzyme Loading and NO-Release Activity.

Nitric oxide (NO) release counteracts platelet aggregation and prevents the thrombosis cascade in the inner walls of blood vessels. NO-release coatings also prevent thrombus formation on the surface of blood-contacting medical devices. Our previous work has shown that inducible nitric oxide synthase (iNOS) films release NO fluxes upon enzymatic conversion of the substrate l-arginine. In this work, we report on the modulation of enzyme loading in layer-by-layer (LbL) thin films of inducible nitric oxide synthase oxygenase (iNOSoxy) on polyethylenimine (PEI). The layer of iNOSoxy is electrostatically adsorbed onto the PEI layer. The pH of the iNOSoxy solution affects the amount of enzyme adsorbed. The overall negative surface charge of iNOSoxy in solution depends on the pH and hence determines the density of adsorbed protein on the positively charged PEI layer. We used buffered iNOSoxy solutions adjusted to pHs 8.6 and 7.0, while saline PEI solution was used at pH 7.0. Atomic force microscopy imaging of the outermost layer shows higher protein adsorption with iNOSoxy at pH 8.6 than with a solution of iNOSoxy at pH 7.0. Graphite electrodes with PEI/iNOSoxy films show higher catalytic currents for nitric oxide reduction mediated by iNOSoxy. The higher enzyme loading translates into higher NO flux when the enzyme-modified surface is exposed to a solution containing the substrate and a source of electrons. Spectrophotometric assays showed higher NO fluxes with iNOSoxy/PEI films built at pH 8.6 than with films built at pH 7.0. Fourier transform infrared analysis of iNOSoxy adsorbed on PEI at pH 8.6 and 7.0 shows structural differences of iNOSoxy in films, which explains the observed changes in enzymatic activity. Our findings show that pH provides a strategy to optimize the NOS loading and enzyme activity in NOS-based LbL thin films, which enables improved NO release with minimum layers of PEI/NOS.

Synthesis and Characterization of Cobalt(II) N,N'-Diphenylazodioxide Complexes.

Removal of chloride from CoCl2 with TlPF6 in acetonitrile, followed by addition of excess nitrosobenzene, yielded the eight-coordinate cobalt(II) complex salt [Co{Ph(O)NN(O)Ph}4](PF6)2, shown by single-crystal X-ray analysis to have a distorted tetragonal geometry. The analogous treatment of the bipyridyl complex Co(bpy)Cl2 yielded the mixed-ligand cobalt(II) complex salt [Co(bpy){Ph(O)NN(O)Ph}2](PF6)2, whose single-crystal X-ray structure displays a trigonal prismatic geometry, similar to that of the iron(II) cation in the previously known complex salt [Fe{Ph(O)NN(O)Ph}3](FeCl4)2. The use of TlPF6 to generate solvated metal complex cations from chloride salts or chlorido complexes, followed by the addition of nitrosobenzene, is shown to be a useful synthetic strategy for the preparation of azodioxide complex cations with the noncoordinating, diamagnetic PF6 - counteranion. Coordination number appears to be more important than d electron count in determining the geometry and metal-ligand bond distances of diphenylazodioxide complexes.