Phenanthrene sorption studies on coffee waste- and diatomaceous earth-based adsorbents, and adsorbent regeneration with cold atmospheric plasma.

Phenanthrene (PHE) is a polycyclic aromatic hydrocarbon categorized as a high priority organic pollutant being toxic for the ecosystem and human health, and its sorption on natural organic or inorganic substances seems a well-promising method for its removal from water streams. The goals of the present work are (i) to assess the capacity of low-cost adsorbents fabricated by treating coffee wastes and diatomaceous earth to remove PHE from water; (ii) to elucidate the role of the pore structure on PHE sorption dynamics; and (iii) to assess the potential to regenerate adsorbents loaded with PHE, by using the novel technology of cold atmospheric plasma (CAP). Diatomaceous earth (DE) and DE pre-treated with sodium hydroxide (NaOH) or phosphoric acid (H3PO4) were chosen as inorganic adsorbents. Coffee waste (CW) and activated carbons (AC) produced from its pyrolysis at 800 °C (CWAC), either untreated (CWAC-800) or pre-treated with NaOH (CWAC-NaOH-800) and H3PO4 (CWAC-H3PO4-800), were chosen as organic adsorbents. The adsorbents were characterized with nitrogen adsorption-desorption isotherms, attenuated total reflectance-Fourier transform infrared spectroscopy, Raman spectroscopy, scanning electron microscopy, and mercury intrusion porosimetry. Based on the PHE sorption capacity and pore structure/surface characteristics, the CWAC-NaOH-800 was chosen as the most efficient adsorbent for further equilibrium and kinetic sorption studies. The multi-compartment model was used to describe the PHE sorption dynamics in CWAC-NaOH-800 by accounting for the pore/surface diffusion and instantaneous sorption. The CWAC-NaOH-800 exhibited remarkable values for (i) the specific surface area (SBET = 676.5 m2/g) and meso- and micro-pore volume determined by nitrogen sorption (VLN2 = 0.415 cm3/g); (ii) the macro- and meso-pore volume determined by mercury intrusion porosimetry (VMIP = 3.134 cm3/g); and (iii) the maximum PHE sorption capacity (qmax = 142 mg/g). The percentage of adsorbent recovery after its regeneration with CAP was found to be ~ 35%. From the simulation of sorption dynamics, it was found that at early times, the sorption kinetics is governed by the film diffusion towards the external surface of grains, but at late times, most of the adsorbed mass is transferred primarily to meso-/macro-pores via diffusion, and secondarily to micro-porosity via surface diffusion. Based on the adsorbent characteristics, effect of pH on sorption efficiency, and numerical analysis of sorption dynamics, it was concluded that probably the dominant adsorption mechanism is the π-π interactions between hydrophobic PHE aromatic rings and CWAC-NaOH-800 graphene layers. The high PHE removal efficiency of CWAC-NaOH-800, the successful interpretation of sorption dynamics with the multi-compartment model, and the potential to regenerate PHE-loaded adsorbents with the green and economic technology of CAP motivate a strategy for testing CWACs towards the adsorption of other PAHs, application of adsorbents to real wastewaters, and scaling-up to pilot units.

Identification of a Dual Inhibitor of Secreted Phospholipase A2 (GIIA sPLA2) and SARS-CoV-2 Main Protease.

The development of novel agents to combat COVID-19 is of high importance. SARS-CoV-2 main protease (Mpro) is a highly attractive target for the development of novel antivirals and a variety of inhibitors have already been developed. Accumulating evidence on the pathobiology of COVID-19 has shown that lipids and lipid metabolizing enzymes are critically involved in the severity of the infection. The purpose of the present study was to identify an inhibitor able to simultaneously inhibit both SARS-CoV-2 Mpro and phospholipase A2 (PLA2), an enzyme which plays a significant role in inflammatory diseases. Evaluating several PLA2 inhibitors, we demonstrate that the previously known potent inhibitor of Group IIA secretory PLA2, GK241, may also weakly inhibit SARS-CoV-2 Mpro. Molecular mechanics docking and molecular dynamics calculations shed light on the interactions between GK241 and SARS-CoV-2 Mpro. 2-Oxoamide GK241 may represent a lead molecular structure for the development of dual PLA2 and SARS-CoV-2 Mpro inhibitors.

N-Acylated and N-Alkylated 2-Aminobenzothiazoles Are Novel Agents That Suppress the Generation of Prostaglandin E2.

The quest for novel agents to regulate the generation of prostaglandin E2 (PGE2) is of high importance because this eicosanoid is a key player in inflammatory diseases. We synthesized a series of N-acylated and N-alkylated 2-aminobenzothiazoles and related heterocycles (benzoxazoles and benzimidazoles) and evaluated their ability to suppress the cytokine-stimulated generation of PGE2 in rat mesangial cells. 2-Aminobenzothiazoles, either acylated by the 3-(naphthalen-2-yl)propanoyl moiety (GK510) or N-alkylated by a chain carrying a naphthalene (GK543) or a phenyl moiety (GK562) at a distance of three carbon atoms, stand out in inhibiting PGE2 generation, with EC50 values ranging from 118 nM to 177 nM. Both GK510 and GK543 exhibit in vivo anti-inflammatory activity greater than that of indomethacin. Thus, N-acylated or N-alkylated 2-aminobenzothiazoles are novel leads for the regulation of PGE2 formation.

Synthesis of benzoxazole-based vorinostat analogs and their antiproliferative activity.

Hydroxamic acid derivatives constitute an interesting novel class of antitumor agents. Three of them, including vorinostat, are approved drugs for the treatment of malignancies, while several others are currently under clinical trials. In this work, we present new vorinostat analogs containing the benzoxazole ring as the cap group and various linkers. The benzoxazole-based analogs were synthesized starting either from 2-aminobenzoxazole, through conventional coupling, or from benzoxazole, through a metal-free oxidative amination. All the synthesized compounds were evaluated for their antiproliferative activity on three diverse human cancer cell lines (A549, Caco-2 and SF268), in comparison to vorinostat. Compound 12 (GK601), carrying a benzoxazole ring replacement for the phenyl ring of vorinostat, was the most potent inhibitor of the growth of three cell lines (IC50 1.2-2.1 µΜ), similar in potency to vorinostat. Compound 12 also inhibited human HDAC1, HDAC2 and HDAC6 like vorinostat. This new analog also showed antiproliferative activity against two colon cancer cell lines genetically resembling pseudomyxoma peritonei (PMP), namely HCT116 GNAS R201C/+ and LS174T (IC50 0.6 and 1.4 µΜ, respectively) with potency comparable to vorinostat (IC50 1.1 and 2.1 µΜ, respectively).

α-Ketoheterocycles Able to Inhibit the Generation of Prostaglandin E2 (PGE2) in Rat Mesangial Cells.

Prostaglandin E2 (PGE2) is a key mediator of inflammation, and consequently huge efforts have been devoted to the development of novel agents able to regulate its formation. In this work, we present the synthesis of various α-ketoheterocycles and a study of their ability to inhibit the formation of PGE2 at a cellular level. A series of α-ketobenzothiazoles, α-ketobenzoxazoles, α-ketobenzimidazoles, and α-keto-1,2,4-oxadiazoles were synthesized and chemically characterized. Evaluation of their ability to suppress the generation of PGE2 in interleukin-1ß plus forskolin-stimulated mesangial cells led to the identification of one α-ketobenzothiazole (GK181) and one α-ketobenzoxazole (GK491), which are able to suppress the PGE2 generation at a nanomolar level.

Photocatalytic Degradation of Dissolved Phenol by Immobilized Zinc Oxide Nanoparticles: Batch Studies, Continuous Flow Experiments, and Numerical Modeling.

In spite of the progress achieved on the photo-catalytic treatment of water streams, there is still a gap of knowledge on the optimization of the performance of continuous-flow photo-reactors. Zinc-oxide (ZnO) nanoparticles were immobilized on Duranit (80% silica + 20% alumina) inert balls with dip-coating and thermal annealing. The immobilized ZnO nanoparticles were characterized by scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), X-ray diffraction (XRD), ultraviolet-visible (UV-Vis) spectroscopy, and Raman spectroscopy. To assess the stability and photocatalytic capacity of immobilized ZnO, degradation tests of phenol were performed in batch mode in a 22 W UV-oven with an emission peak at 375 nm by varying the temperature, the initial phenol concentration, and the ratio of photocatalyst mass to initial phenol mass. Continuous flow tests were conducted on two types of annular photo-reactors, made of poly(methyl)methacrylate (PMMA) and stainless steel (STST), equipped with a 6 W UV-lamp with emission at 375 nm, packed with ZnO-coated Duranit beads. Experiments were conducted by recirculating the phenol solution between the annular space of reactor and an external tank and varying the flow rate and the liquid volume in the tank. A one-dimensional dynamic mathematical model was developed by combining reactive with mass-transfer processes and used to estimate the overall reaction kinetic constant with inverse modeling. The results revealed that the ZnO losses might be discernible in batch mode due to the intense stirring caused by the bubbles of injected air, while an insignificant loss of ZnO mass occurs under continuous flow conditions, even after several cycles of reuse; the order of the overall phenol photodegradation reaction is lower than unity; the pseudo-1st order kinetic constant scales positively with the ratio of photocatalyst mass to the initial phenol mass and Peclet number.

Aldehydes as powerful initiators for photochemical transformations.

Photochemistry, the use of light to promote organic transformations, has been known for more than a century but only recently has revolutionized the way modern chemists are thinking. Except from transition metal-based complexes, small organic molecules have been introduced as catalysts or initiators. In this review, we summarize the potential that (aromatic or aliphatic) aldehydes have as photoinitiators. The photophysical properties and photoreactivity of benzaldehyde are initially provided, followed by applications of aldehydes as initiators for polymerization reactions. Finally, the applications to date regarding aldehydes as photoinitiators in organic synthesis are presented.

Combining experimental techniques with non-linear numerical models to assess the sorption of pesticides on soils.

The risk assessment of groundwater pollution by pesticides may be based on pesticide sorption and biodegradation kinetic parameters estimated with inverse modeling of datasets from either batch or continuous flow soil column experiments. In the present work, a chemical non-equilibrium and non-linear 2-site sorption model is incorporated into solute transport models to invert the datasets of batch and soil column experiments, and estimate the kinetic sorption parameters for two pesticides: N-phosphonomethyl glycine (glyphosate) and 2,4-dichlorophenoxy-acetic acid (2,4-D). When coupling the 2-site sorption model with the 2-region transport model, except of the kinetic sorption parameters, the soil column datasets enable us to estimate the mass-transfer coefficients associated with solute diffusion between mobile and immobile regions. In order to improve the reliability of models and kinetic parameter values, a stepwise strategy that combines batch and continuous flow tests with adequate true-to-the mechanism analytical of numerical models, and decouples the kinetics of purely reactive steps of sorption from physical mass-transfer processes is required.

Soil column experiments used as a means to assess transport, sorption, and biodegradation of pesticides in groundwater.

Soil column experiments are used to investigate the fate of three pesticides of high, intermediate, and low solubility in groundwater: N- phosphonomethyl glycine (glyphosate); O,O-diethyl-S-[(ethylthio)methyl]phosphorodithioate (phorate); (2,4-dichlorophenoxy)acetic acid (2,4-D). Feed solutions are prepared by adding each pesticide (100 mg/L glyphosate, 50 micro g/L phorate, 50 mg/L 2,4-D) along with conservative tracer, KBr, in synthetic groundwater. The concentration of the pesticides in effluents is detected by ion chromatography (glyphosate, 2,4-D) and GC-FID (phorate). The Br(-) breakthrough curves are employed to estimate the dispersion coefficient and mean pore velocity in each column. Solute transport and reactive models accounting for equilibrium/non-equilibrium sorption and biodegradation are coupled with inverse modeling numerical codes to estimate the kinetic parameters for all pesticides.

Thyrotropin-releasing hormone administration does not affect seizure threshold during electroconvulsive therapy.

SUMMARY: Despite the fact that a role for thyrotropin-releasing hormone (TRH) in seizure modulation has been consistently hypothesized, the exact nature of this role remains unclear. In this study, we investigated the effects of TRH administration on seizure threshold and seizure duration in 13 depressed inpatients undergoing electroconvulsive therapy (ECT). In a balanced order crossover design, an intravenous bolus of 0.4 mg TRH or placebo was administered immediately before anesthesia, during the first two sessions, in a series of bilateral ECT. In both of these sessions, a threshold titration procedure was applied by using gradual increments of the electrical charge delivered until seizure elicitation, a procedure that has been safely used in the past. Seizure threshold was defined as the lowest energy level required for induction of a grand mal seizure, by use of this titration procedure. Seizure duration was estimated both by simultaneous EEG recording and by the cuff method. Results showed that neither seizure threshold, nor seizure duration (either by cuff or by EEG) differed between the TRH and the placebo conditions, regardless of the order in which TRH or placebo were administered in the two ECT sessions. This was the case regardless of whether the patients had at baseline a blunted TSH response to TRH or not. Our findings do not support a role for TRH on seizure modulation, at least when TRH is administered exogenously. Such an effect, if it exists, could be obscured, however, by several factors, including pharmacokinetics.