Exposure to Microplastics Made of Plasmix-Based Materials at Low Amounts Did Not Induce Adverse Effects on the Earthworm Eisenia foetida.

The implementation of recycling techniques represents a potential solution to the plastic pollution issue. To date, only a limited number of plastic polymers can be efficiently recycled. In the Italian plastic waste stream, the residual, non-homogeneous fraction is called 'Plasmix' and is intended for low-value uses. However, Plasmix can be used to create new materials through mechanical recycling, which need to be tested for their eco-safety. This study aimed to investigate the potential toxicity of two amounts (0.1% and 1% MPs in soil weight) of microplastics (MPs) made of naïve and additivated Plasmix-based materials (Px and APx, respectively) on the earthworm Eisenia foetida. Changes in oxidative status and oxidative damage, survival, gross growth rate and reproductive output were considered as endpoints. Although earthworms ingested both MP types, earthworms did not suffer an oxidative stress condition or growth and reproductive impairments. The results suggested that exposure to low amounts of both MPs can be considered as safe for earthworms. However, further studies testing a higher amount or longer exposure time on different model species are necessary to complete the environmental risk assessment of these new materials.

Comparison of the potential toxicity induced by microplastics made of polyethylene terephthalate (PET) and polylactic acid (PLA) on the earthworm Eiseniafoetida.

A growing number of studies have demonstrated that microplastic (MP) contamination is widespread in terrestrial ecosystems. A wide array of MPs made of conventional, fossil-based polymers differing in size and shape has been detected in soils worldwide. Recently, also MPs made of bioplastics have been found in soils, but there is a dearth of information concerning their toxicity on soil organisms. This study aimed at exploring the potential toxicity induced by the exposure for 28 days to irregular shaped and differently sized MPs made of a fossil-based (polyethylene terephthalate - PET) and a bioplastic (polylactic acid - PLA) polymer on the earthworm Eisenia foetida. Two amounts (1 g and 10 g/kg of soil, corresponding to 0.1% and 1% of soil weight) of both MP types were administered to the earthworms. A multi-level approach was used to investigate the MP-induced effects at sub-individual and individual level. Changes in the activity of antioxidant and detoxifying enzymes, as well as in lipid peroxidation levels, were investigated at specific time-points (i.e., 7, 14, 21 and 28 days) as sub-individual responses. Histological analyses were performed to assess effects at tissue level, while the change in digging activity was considered as a proxy of behavioral effects. Earthworms ingested MPs made of both the polymers. MPs made of PET did not induce any adverse effect at none of the biological levels. In contrast, MPs made of PLA caused the modulation of earthworms' oxidative status as showed by a bell-shaped activity of superoxide dismutase coupled with an increase in glutathione peroxidase activity. However, neither oxidative and tissue damage, nor behavioral alteration occurred. These findings suggest that the exposure to bio-based MPs can cause higher toxicity compared to fossil-based MPs.

Unveiling the multilevel impact of four water-soluble polymers on Daphnia magna: From proteome to behaviour (a case study).

The ubiquitous presence of water-soluble polymers (WSPs) in freshwater environments raises concerns regarding potential threats to aquatic organisms. This study investigated, for the first time, the effects of widely used WSPs -polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), polyacrylic acid (PAA), and polyethylene glycol (PEG)- using a multi-level approach in the freshwater biological model Daphnia magna. This integrated assessment employed a suite of biomarkers, evaluation of swimming behaviour, and proteomic analysis to investigate the effects of three environmentally relevant concentrations (0.001, 0.5, and 1 mg/L) of the tested WSPs from molecular to organismal levels, assessing both acute and chronic effects. Our findings reveal that exposure to different WSPs induces specific responses at each biological level, with PEG being the only WSP inducing lethal effects at 0.5 mg/L. At the physiological level, although all WSPs impacted both swimming performance and heart rate of D. magna specimens, PAA exhibited the greatest effects on the measured behavioural parameters. Furthermore, proteomic analyses demonstrated altered protein profiles following exposure to all WSPs, with PVA emerging as the most effective.

Assessment of behavioural effects of three water-soluble polymers in zebrafish embryos.

The water-soluble polymers (WSPs) are widely used in many industrial applications and are present in several commonly used products due to their physical-chemical characteristics: as their name indicates, despite being synthetic polymers, they are able to solubilize in water. Because of this peculiar property, both the qualitative-quantitative evaluation in aquatic ecosystems and their potential (eco)toxicological effects have been neglected until now. The aim of this study was to evaluate the possible effects of three of the most widely used WSPs as polyacrylic acid (PAA), polyethylene glycol (PEG) and polyvinyl pyrrolidone (PVP) on the swimming behaviour of zebrafish (Danio rerio) embryos after the exposure to different concentrations (0.001, 0.5, 1 mg/L). The exposure lasted from the eggs' collection up to 120 h post fertilization (hpf) also using three different light intensity (300 lx, 2200 lx, 4400 lx) to better evaluate any effects related to different gradients of light/dark transitions. In order to analyze individual behavioural changes in embryos, their swimming movements were tracked and a number of parameters for locomotion and directionality were quantified. The main results showed that all three WSPs resulted in significant (p ≤ 0.05) variations in different movement parameters, suggesting a possible toxicity scale: PVP > PEG â‰« PAA.

Synthesis and Characterization of Curcumin-Loaded Nanoparticles of Poly(Glycerol Sebacate): A Novel Highly Stable Anticancer System.

The research for alternative administration methods for anticancer drugs, towards enhanced effectiveness and selectivity, represents a major challenge for the scientific community. In the last decade, polymeric nanostructured delivery systems represented a promising alternative to conventional drug administration since they ensure secure transport to the selected target, providing active compounds protection against elimination, while minimizing drug toxicity to non-target cells. In the present research, poly(glycerol sebacate), a biocompatible polymer, was synthesized and then nanostructured to allow curcumin encapsulation, a naturally occurring polyphenolic phytochemical isolated from the powdered rhizome of Curcuma longa L. Curcumin was selected as an anticancer agent in virtue of its strong chemotherapeutic activity against different cancer types combined with good cytocompatibility within healthy cells. Despite its strong and fascinating biological activity, its possible exploitation as a novel chemotherapeutic has been hampered by its low water solubility, which results in poor absorption and low bioavailability upon oral administration. Hence, its encapsulation within nanoparticles may overcome such issues. Nanoparticles obtained through nanoprecipitation, an easy and scalable technique, were characterized in terms of size and stability over time using dynamic light scattering and transmission electron microscopy, confirming their nanosized dimensions and spherical shape. Finally, biological investigation demonstrated an enhanced cytotoxic effect of curcumin-loaded PGS-NPs on human cervical cancer cells compared to free curcumin.

Microplastic contamination of supraglacial debris differs among glaciers with different anthropic pressures.

Microplastic (MP) contamination is ubiquitous and widespread in terrestrial and aquatic ecosystems, including remote areas. However, information on the presence and distribution of MPs in high-mountain ecosystems, including glaciers, is still limited. The present study aimed at investigating presence, spatial distribution, and patterns of contamination of MPs on three glaciers of the Ortles-Cevedale massif (Central Alps, Northern Italy) with different anthropic pressures, i.e., the Forni, Cedec and Ebenferner-Vedretta Piana glaciers. Samples of supraglacial debris were randomly collected from the glaciers and MPs were isolated. The mean amount (±SE) of MPs measured in debris from Forni, Cedec and Ebenferner-Vedretta Piana glaciers was 0.033 ± 0.007, 0.025 ± 0.009, and 0.265 ± 0.027 MPs g-1 dry weight, respectively. The level and pattern of MP contamination from the Ebenferner-Vedretta Piana glacier were significantly different from those of the other glaciers. No significant spatial gradient in MP distribution along the ablation areas of the glaciers was observed, suggesting that MPs do not accumulate toward the glacier snout. Our results confirmed that local contamination can represent a relevant source of MPs in glacier ecosystems experiencing high anthropic pressure, while long-range transport can be the main source on other glaciers.

Approaches for Management and Valorization of Non-Homogeneous, Non-Recyclable Plastic Waste.

The environmental accumulation of plastic wastes has become one of the most discussed topics in the scientific community. The development of new strategies to tackle this issue is of crucial importance, and different approaches are being investigated to effectively reduce plastic waste generated by improper or inefficient disposal. In addition to the efforts addressing the development of biodegradable plastics, the research is currently focused on the development of innovative recycling approaches. Indeed, although most plastic materials are potentially recyclable, only 15% of the worldwide plastic waste is currently recycled, while the remaining 85% is usually incinerated to recover thermal energy or landfilled. The hurdles to efficient recycling come from improper management of end-of-life plastic goods. Moreover, the highly heterogeneous nature and versatility of plastic and polymeric materials have led to the development of multilayered materials, composites, blends and many other different species, whose management and/or reprocessing to yield high-value products is extremely challenging. Thus, although these materials are extremely valuable from an industrial point of view, they add a high degree of complexity to the recycling process because each one of them is different from the other, but they cannot be separated efficiently. The aim of the present review is to return a comprehensive overview of environmental and management issues related to the complex and heterogeneous mixture of plastic waste that is generated at the end of the sorting procedures in Italian plastic recycling plants, the so-called 'Plasmix'. This review lists the difficulties and limitations related to the management of non-recyclable Plasmix and highlights the strategies for the proper, sustainable and valuable use of this plastic waste.

Are "liquid plastics" a new environmental threat? The case of polyvinyl alcohol.

Despite the pollution induced by plastics become a well-known and documented problem, bringing many countries to adopt restrictions about their production, commercialization and use, the impact of another emerging category of synthetic polymers, represented by the Water-Soluble Polymers (WSPs), also known as "liquid plastics", is overlooked by scientific community. WSPs are produced in large quantities and used in a wide plethora of applications such as food packaging, pharmaceuticals and personal care products, cosmetics and detergents, with a consequent continuous release in the environment. The aim of this study was the investigation of the possible toxicity induced by polyvinyl alcohol (PVA), one of the main produced and used WSPs, on two freshwater model organisms, the crustacean Daphnia magna and the teleost Danio rerio (zebrafish). We evaluated the effects of solubilized standard PVA powder and PVA-based commercial bags for carp-fishing, at 3 different concentrations (1 µg/L, 0.5 mg/L and 1 mg/L), through the exposures for 14 days of D. magna (daphnids; age < 24 h) and for 5 days of zebrafish embryos (up to 120 h post fertilization - hpf). As acute effects we evaluated the immobilization/mortality of specimens, while for chronic toxicity we selected several endpoints with a high ecological relevance, as the behavioural alteration on swimming performance, in real-time readout, and the activity of monoamine oxidase (MAO), a neuro-enzyme with a potential implication in the organism movement. The results showed the lack of significant effects induced by the selected substances, at all tested concentrations and in both model organisms. However, considering the wide plethora of available WSPs, other investigations are needed to provide the initial knowledge of risk assessment of these compounds contained in some consumer products.

Highly diastereoselective entry to chiral oxindole-based ß-amino boronic acids and spiro derivatives.

We here describe the first Cu-catalysed, diastereoselective 1,2-addition of 1,1-diborylmethane to chiral ketimines for the synthesis of quaternary stereocenters and spiro compounds. The method provides easy access to a range of chiral, highly functionalized compounds, namely oxindole-based ß,ß'-disubstituted ß-amino boronates, boron-containing peptidomimetics and six-, seven-membered spirocyclic hemiboronic esters. Such unprecedented compounds are mostly obtained in high yields and easily isolated as single diastereoisomers, paving the way to a more intense exploitation of boron-containing compounds in diversity-oriented chemistry and drug-discovery programs. Concerning stereochemistry, the application of Ellman's auxiliary strategy allows in principle to access both steric series of target compounds.

1,3-Dioxolan-4-Ones as Promising Monomers for Aliphatic Polyesters: Metal-Free, in Bulk Preparation of PLA.

The first example of solvent-free, organocatalyzed, polymerization of 1,3-dioxolan-4-ones, used as easily accessible monomers for the synthesis of polylactic acid (PLA), is described here. An optimization of reaction conditions was carried out, with p-toluensulfonic acid emerging as the most efficient Brønsted acid catalyst. The reactivity of the monomers in the tested conditions was studied following the monomer conversion by 1H NMR and the molecular weight growth by SEC analysis. A double activation polymerization mechanism was proposed, pointing out the key role of the acid catalyst. The formation of acetal bridges was demonstrated, to different extents depending on the nature of the aldehyde or ketone employed for lactic acid protection. The polymer shows complete retention of stereochemistry, as well as good thermal properties and good polydispersity, albeit modest molecular weight.

Interactive effects between sinking polyethylene terephthalate (PET) microplastics deriving from water bottles and a benthic grazer.

The information concerning the toxicity of sinking microplastics (MPs) on benthic marine animals, particularly benthic grazers, is still scant. No study focused on biological weathering of sinked MPs operated by benthic organisms. This study aims at investigating the ingestion and the effects induced by 7-days dietary exposure to environmentally relevant amount (8, 80 and 800 particles/g of food) of irregular shaped and sized (diameter 12.6-1,065 µm; mean diameter 316 ± 12 µm) polyethylene terephthalate microplastics (PET-MPs) on a common marine benthic grazer, the sea urchin Paracentrotus lividus. Adverse effects were investigated on digestive tract at biochemical (oxidative stress biomarkers) and tissue level (histopathological analyses). Potential alteration of MP structure/surface and PET macromolecules due to the ingestion of PET-MPs within the sea urchin digestive tract were investigated. Results showed that PET-MPs were efficiently egested by sea urchins without producing histological alterations on digestive tract tissues, only inducing a slight modulation of oxidative status. Sea urchin grazing activity and the related transit of PET-MPs within animal digestive tract slightly affected MP structure and PET composition. These findings suggest that PET-MPs might represent an hazard for benthic grazer organisms, which can partially contribute to the degradation of PET in marine ecosystems.

Synthesis of Polylactic Acid Initiated through Biobased Antioxidants: Towards Intrinsically Active Food Packaging.

Polylactide (PLA)-based polymers, functionalized with biobased antioxidants, were synthesized, to develop an intrinsically active, biobased and potentially biodegradable material for food packaging applications. To achieve this result, phenolic antioxidants were exploited as initiators in the ring opening polymerization of l-lactide. The molecular weight, thermal properties and in vitro radical scavenging activity of the polymers obtained were compared with the ones of a PLA Natureworks 4043D, commonly used for flexible food packaging applications. The most promising synthesized polymer, bearing vanillyl alcohol as initiator (PLA-VA), was evaluated for active food packaging applications. Packaging with PLA-VA films reduced color and fat oxidation of salami during its shelf life.

Isonitrile-Based Multicomponent Synthesis of ß-Amino Boronic Acids as ß-Lactamase Inhibitors.

The application of various isonitrile-based multicomponent reactions to protected (2-oxoethyl)boronic acid (as the carbonyl component) is described. The Ugi reaction, both in the four components and in the four centers-three components versions, and the van Leusen reaction, proved effective at providing small libraries of MIDA-protected ß-aminoboronic acids. The corresponding free ß-aminoboronic acids, quantitatively recovered through basic mild deprotection, were found to be quite stable and were fully characterized, including by 11B-NMR spectroscopy. Single-crystal X-ray diffraction analysis, applied both to a MIDA-protected and a free ß-aminoboronic acid derivative, provided evidence for different conformations in the solid-state. Finally, the antimicrobial activities of selected compounds were evaluated by measuring their minimal inhibitory concentration (MIC) values, and the binding mode of the most promising derivative on OXA-23 class D ß-lactamase was predicted by a molecular modeling study.

Oxidative stress-related effects induced by micronized polyethylene terephthalate microparticles in the Manila clam.

Microplastic (MP) contamination represents a serious threat for marine organisms. Several lab studies demonstrated adverse effects induced by exposure to different MP polymers toward diverse marine species. However, the information regarding toxicity of polyethylene terephthalate (PET) MPs is largely unknown. The present study was aimed at investigating the adverse effects induced by 7-day exposure to two concentrations (0.125 or 12.5 µg/ml) micronized, irregular shaped and variable size PET microparticles (PET-MPs) toward Manila clam (Ruditapes philippinarum). Histological analyses were performed to assess tissue damage on digestive glands, gonads, gut and gills, whereas oxidative stress-related effects, including the concentration of pro-oxidant molecules, activity of antioxidant (superoxide dismutase - SOD, catalase - CAT and glutathione peroxidase - GPx) and detoxifying (glutathione S-transferase - GST) enzymes, as well as levels of lipid peroxidation, were determined in gills and digestive gland. Our results showed that clams ingest and egest micronized PET-MPs, but no marked histological alterations to bivalve tissues occurred. Although PET-MPs did not produce oxidative stress in the digestive gland, these materials significantly altered oxidative status of gills, leading to lipid peroxidation. No apparent clear indication of a weakness of bivalve health status was obtained in this study.

Fast Production of Cellulose Nanocrystals by Hydrolytic-Oxidative Microwave-Assisted Treatment.

In contrast to conventional approaches, which are considered to be energy- and time-intensive, expensive, and not green, herein, we report an alternative microwave-assisted ammonium persulfate (APS) method for cellulose nanocrystals (CNCs) production, under pressurized conditions in a closed reaction system. The aim was to optimize the hydrolytic-oxidative patented procedure (US 8,900,706), replacing the conventional heating with a faster process that would allow the industrial scale production of the nanomaterial and make it more appealing to a green economy. A microwave-assisted process was performed according to different time-temperature programs, varying the ramp (from 5 to 40 min) and the hold heating time (from 60 to 90 min), at a fixed reagent concentration and weight ratio of the raw material/APS solution. Differences in composition, structure, and morphology of the nanocrystals, arising from traditional and microwave methods, were studied by several techniques (TEM, Fourier transform infrared spectroscopy (FTIR)-attenuated total reflectance (ATR), dynamic light scattering (DLS), electrophoretic light scattering (ELS), thermogravimetric analysis (TGA), X-ray diffraction (XRD)), and the extraction yields were calculated. Fine tuning the microwave treatment variables, it was possible to realize a simple, cost-effective way for faster materials' preparation, which allowed achieving high-quality CNCs, with a defined hydrodynamic diameter (150 nm) and zeta potential (-0.040 V), comparable to those obtained using conventional heating, in only 90 min instead of 16 h.

Exploitation of the Ugi-Joullié reaction in drug discovery and development.

Introduction: Multicomponent reactions are paramount in drug discovery for their ability to achieve high levels of diversity within the chemical space, generating complex structures from simple building blocks. Among them, the isocyanide-based Ugi-Joulliè reaction is particularly suited for the rapid synthesis of peptidomimetics and nitrogen-containing compounds. Areas covered: The latest achievements in drug discovery and synthetic chemistry regarding the application of the Ugi-Joulliè reaction in the field of natural compounds, peptidomimetics and small molecules, are reported in this article. All relevant literature was disclosed applying most common web-based literature searching tools, namely Web of Science, PubMed, SciFinder and Google Scholar. Expert opinion: The Ugi-Joulliè reaction represents an extremely versatile and simple synthetic methodology, useful for designing efficiently new molecular frameworks. Particularly relevant to drug discovery is the Ugi-Joulliè-based synthesis of conformationally constrained peptidomimetics and antibacterial depsipeptides. On the other hand, the many syntheses of new, nitrogen-containing heterocycles are not always followed by biological evaluation, losing opportunities for the disclosure of unprecedented lead compounds.

Allylation of isatin-derived N-Boc-hydrazones followed by Pd-catalyzed carboamination reaction: an entry to 3-spiro-pyrazolidyl-oxindoles.

The indium-mediated allylation of novel 3-(2-Boc-hydrazono)indolin-2-one derivatives, followed by a palladium-catalysed carboamination reaction, is described to afford unprecedented spirocyclic oxindoles in good yields. The method provides an efficient access to both cis and trans diastereoisomers of highly functionalized compounds, bearing an N-Boc, 5-substituted pyrazolidine ring at the C3-oxindole spiro junction. The versatility of the method is fully demonstrated starting from a series of substituted isatins and employing a variety of aryl halides in the key cyclization step.