Search Results (93)

The extraction of rare earth elements is becoming increasingly essential due to their many applications in current and emerging advanced material technologies. However, in many rare earth deposits, rare earth minerals are associated with radionuclides; specifically, thorium and uranium. The radioactive nature of these elements is a major concern during processing. Techniques such as solvent extraction and precipitation have been employed in this regard to minimize the radioactivity levels and address any related processing or environmental concerns. However, they face various challenges such as high chemical reagent consumption, secondary waste generation, and limited selectivity, which hinder either their scalability or sustainability. The current study provides a literature review about these technologies to provide critical insights on their applications and discuss the challenges hampering their extensive use in the mining industry. Biotechnology is also evaluated and highlighted as a promising, cost-effective, and low-environmental-impact option for the selective recovery of radionuclides from rare earth elements. Specifically, pyoverdine siderophores were discussed due to their catecholates and hydroxamate moieties which have high affinity for radionuclides to enhance selective recovery during rare earth processing. Conversely, integration of this approach into existing mineral processing flowsheets is a constraint. Hence, future studies should focus on optimizing the kinetics of siderophore synthesis and explore a hybrid approach to combine the biotechnological and conventional techniques. Full article

Urinary tract infections (UTIs) are common and create significant clinical challenges. Most UTIs are caused by uropathogenic Escherichia coli (UPEC) and affect 50 to 70% of women at some point in their lives. Of this population, 25% will have a recurrent urinary tract infection (rUTI) within 3 to 12 months of the first episode. High rates of rUTIs may occur because UPEC can enter a non-proliferative or quiescent state within the urothelium of the bladder. This state allows UPEC to evade the host’s immune response and antibiotic treatment. We utilized a library of plant extracts derived from the URI Heber W. Youngken Jr. Medicinal Garden to determine if they reversed UPEC quiescence with a novel in vitro quiescence assay using the classic UPEC endemic lineage ST73 strain CFT073. We found an overall active extract hit rate of 69% (79/114 active) and that active extracts contained high levels of polyphenolic compounds. Further testing showed that polyphenols with adjacent hydroxyl groups on a benzene ring (catechol moiety) were the most effective and potent in reversing quiescence. The ability to reverse quiescence was also linked to the compound’s ability to bind iron (e.g., epigallocatechin gallate and rosmarinic acid were the most potent reversing agents—0.1 mM—and they both had the strongest iron-binding activity as determined via CAS assay). These findings reveal a new class of metabolites that can reverse quiescence in UPEC strains. Full article

A series of rivastigmine hybrids, incorporating rivastigmine fragments (RIV) and a set of different antioxidant scaffolds, were designed, synthesized, and evaluated as multifunctional agents for the potential therapy of Alzheimer’s disease (AD). In vitro bioactivity assays indicated that some compounds have very good antioxidant (radical-scavenging) activity. The compounds also displayed good inhibitory activity against cholinesterases, though the bigger-sized hybrids showed higher inhibitory ability for butyrylcholinesterase (BChE) than for acetylcholinesterase (AChE), due to the larger active site cavity of BChE. All the hybrids exhibited an inhibition capacity for self-induced amyloid-β (Aβ_1–42) aggregation. Furthermore, cell assays demonstrated that some compounds showed capacity for rescuing neuroblastoma cells from toxicity induced by reactive oxygen species (ROS). Among these RIV hybrids, the best in vitro multifunctional capacity was found for the caffeic acid derivatives enclosing catechol moieties (4AY5, 4AY6), though the Trolox derivatives (4AY2, 4BY2) presented the best cell neuroprotective activity against oxidative damage. Molecular-docking studies provided structural insights into the binding modes of RIV-based hybrids to the cholinesterases, revealing key interaction patterns despite some lack of correlation with inhibitory potency. Overall, the balanced multifunctional profiles of these hybrids render them potentially promising candidates for treating AD, thus deserving further investigation. Full article

Novel lipophilic hydroxyalkyl esters were synthetized by Fischer esterification in good to excellent yields (60–96%) from a panel of hydroxyphenylacetic acids and increasing chain length (2 to 8 carbon atoms) α,ω-diols. The in vitro antioxidant activity of these compounds was evaluated by DPPH and ABTS assays. Hydroxybutyl esters and hydroxyphenylacetic acids were used as starting materials for the synthesis of novel lipophilic diesters (butyl diarylacetates) using Mitsunobu reaction. The final products were isolated in moderate to good yields (40–78%), and their structure–antioxidant activity relationships are discussed. Compounds bearing the catechol moiety on one of the two aromatic rings and high lipophilicity proved to be the strongest antioxidants and were selected for testing as antibacterials against Staphylococcus aureus and Escherichia coli, obtaining preliminary and promising results. Full article

Metal chelation to bioactive small molecules is a well-established strategy to enhance the biological activity of the resulting complexes. Among the widely explored structural motifs, the combination of prominent metal centers with naturally inspired derivatives has attracted considerable attention. One such promising platform is the flavone scaffold, derived from flavonoids and studied since ancient times. Flavones are plant-derived compounds known for their diverse biological activities and health benefits. They exhibit significant structural variability, primarily through backbone modifications such as hydroxylation. Importantly, coordination of metal ions to hydroxylated flavone cores often improves their natural bioactivities, including anticancer and antimicrobial effects. In this review, we summarize transition metal complexes incorporating hydroxyflavone (OH–F) ligands reported over the past 15 years. We provide a concise overview of synthetic approaches and structural characterization, with a particular emphasis on coordination modes (e.g., maltol-type, acetylacetonate-type, catechol-type, and others). Furthermore, we discuss biological evaluation results, especially anticancer and antimicrobial studies, to highlight the therapeutic potential of these complexes. Finally, we suggest directions for the future development of metal-based agents bearing hydroxyflavone moieties through several critical points in terms of the accuracy, reproducibility, and relevance of biological studies involving metal-based compounds. Full article

Retinal degenerative processes such as age-related macular degeneration are at the center of many ongoing research studies, as their impact on the general population is significant, with severe visual impairment and even irreversible vision loss if left untreated. Currently, there are few efficient treatments available to stop or limit its progression. In the present paper, a molecular hybridization approach was employed to develop novel compounds that address this issue. By adding either 2-butenal or a β-ionone-derived residue to the hydrazone-catechol-thiazole scaffold, two compounds were designed and synthesized: 5a and 5b. After being characterized by mass spectrometry and nuclear magnetic resonance, and proving potent antioxidant activity in the in vitro assays, the cytotoxicity evaluation using the ARPE-19, BJ, and A549 cell lines revealed a surprisingly low-dose effect of 5a and the unexpected cytotoxic activity of 5b, despite its β-ionone moiety, known for its significant therapeutic properties. Full article

Reactive oxygen species play a significant role in various pathological conditions, driving the need for novel, potent antioxidants. While polyphenols are known for their antioxidant properties, their limited stability and bioavailability present challenges for therapeutic applications. To address these limitations, a series of novel thiazolyl-polyphenolic compounds was synthesized via a multi-step synthetic route incorporating Hantzsch heterocyclization in the final step. The synthesized compounds 7a–k were structurally characterized using spectroscopic techniques, including NMR, MS, and IR. In silico thermodynamic calculations, including HOMO–LUMO gap and bond dissociation enthalpy (BDE) calculations, revealed a promising antioxidant profile for these compounds and indicated that the substitution in position 2 of the thiazole ring does not substantially influence the antioxidant activity conferred by the catechol moiety in position 4. The antioxidant capacity of the synthesized compounds was experimentally validated using a panel of six distinct assays: two radical scavenging assays (ABTS and DPPH) and four electron transfer-based assays (RP, TAC, FRAP, and CUPRAC). The in vitro evaluation demonstrated that compounds 7j and 7k exhibited significantly enhanced antioxidant activity compared to the established antioxidant standards, ascorbic acid and Trolox. These findings suggest that the strategic modifications in position 2 of the thiazole scaffold represent a promising direction for future research aimed at developing novel therapeutic agents with enhanced antioxidant properties. The present study is limited to the in vitro evaluation of compounds based on the N-methyl substituted thiazole scaffold, but future studies can include modifications such as changing the substituent on the thiazole nitrogen, the hydrazone linker or possible insertion of substituents in position 5 of thiazole ring of substituents with various electronic or physico-chemical properties. Full article

The key challenge in polymer science is developing sustainable synthesis methods using renewable feedstocks. This study explores plant-derived diarylheptanoids with various structures as the building blocks for polyurethane (PU) materials. Diarylheptanoid glucosides isolated from black alder (Alnus glutinosa) bark were hydrolyzed and fractionated to remove sugar moieties. The resulting diarylheptanoids, along with unhydrolyzed analogues and curcumin, were used as biomass-based polyols to synthesize model PU films. Incorporating diarylheptanoids enhanced the mechanical strength and reduced the flexibility of PU due to increased crosslinking, with effects proportional to the OH functionality of the biomass-based polyols. Weight loss, FTIR, and Py-GC-MS/FID analyses revealed that the catechol moieties and the glucosidic bonds are biodegradable structural subunits of diarylheptanoids incorporated into PU films. Rigid polyurethane foams (PURs) incorporating high-OH-functionality diarylheptanoid glucosides such as oregonin demonstrated significantly higher compression strength and less weight loss during non-isothermal thermal analysis in air compared to those of commercial polyol-based foams. A cone calorimeter test showed that the PUR foam with diarylheptanoid derivatives had a lower degradation rate, a longer flame-burning time, 30% less heat emission, and 25% less smoke, indicating improved flame retardancy. Adding 1–2% oregonin-enriched black alder bark extracts to commercial Elastopir 1132/509/0 PUR foam significantly improved its resistance to thermal oxidative aging, outperforming the commercial antioxidant Irganox. Full article

The bioaccessibility of flavonoids is of paramount importance in determining their bioavailability and biological effects. Bioaccessibility is influenced by several aspects, comprising the food matrix and the structure of flavonoids. In the present study, the bioaccessibility of different classes of flavonoids (flavanones, flavones, and flavonols) was investigated after in vitro gastro-intestinal digestion of beverages and vegetables. O-glycosylated flavanones were stable during in vitro digestion and easily released from the food matrix. Otherwise, C-glycosylated flavanones displayed a lower bioaccessibility index. Similarly, flavones exhibited a high bioaccessibility index in beverages and vegetables, with the O-glycosylated forms being more stable than the C-glycosylated. Flavonols displayed different stability under gastro-intestinal conditions depending on their structure. The presence of a catechol moiety in the B-ring, as observed in 3-O-glycosylated quercetins, negatively impacted flavonol stability in comparison with kaempferol derivatives that lack the catechol moiety. Indeed, the presence of more than one sugar or the glycosylation of the OH group in the B-ring improved the digestive stability of quercetin derivatives. For flavonols, a clear food matrix effect was observed by comparing the bioaccessibility in beverages and vegetable foods. These findings may aid in improving the comprehension of the biological effects of flavonoids and flavonoid-rich foods. Full article

A current trend in healthcare research is to discover multifunctional compounds, able to interact with multiple biological targets, in order to simplify multi-drug therapies and improve patient compliance. The aim of this work was to outline the growing demand for innovative multifunctional compounds, achieved through the synthesis, characterisation and SAR evaluation of a series of 2-styrylbenzothiazole derivatives. The six synthesised compounds were studied for their potential as photoprotective, antioxidant, antiproliferative, and anti-inflammatory agents. In order to profile antioxidant activity against various radical species, in vitro DPPH, FRAP and ORAC assays were performed. UV-filtering activity was studied, first in solution and then in formulation (standard O/W sunscreen containing 3% synthesised molecules) before and after irradiation. Compound BZTst6 proved to be photostable, suitable for broad-spectrum criteria, and is an excellent UVA filter. In terms of antioxidant activity, only compound BZTst4 can be considered a promising candidate, due to the potential of the catechol moiety. Both also showed exceptional inhibitory action against the pro-inflammatory enzyme 5-lipoxygenase (LO), with IC₅₀ values in the sub-micromolar range in both activated neutrophils and under cell-free conditions. The results showed that the compounds under investigation are suitable for multifunctional application purposes, underlining the importance of their chemical scaffolding in terms of different biological behaviours. Full article

Nanoparticles (NPs) are receiving increasing interest in biomedical applications. However, due to their large surface area, in physiological environments, they tend to interact with plasma proteins, inducing their agglomeration and ultimately resulting in a substantial efficiency decrease in diagnostic and therapeutic applications. To overcome such problems, NPs are typically coated with a layer of hydrophilic and biocompatible polymers, such as PEG chains. However, few examples exist in which this property could be systematically fine-tuned and combined with added properties, such as emission. Herein, we report a novel mussel-inspired catechol-based strategy to obtain biocompatible and multifunctional coatings, using a previously developed polymerization methodology based on the formation of disulfide bridges under mild oxidative conditions. Two families of NPs were selected as the proof of concept: mesoporous silica NPs (MSNPs), due to their stability and known applications, and magnetite NPs (Fe₃O₄ NPs), due to their small size (<10 nm) and magnetic properties. The PEG coating confers biocompatibility on the NPs and can be further functionalized with bioactive molecules, such as glucose units, through the end carboxylic acid moieties. Once we demonstrated the feasibility of our approach to obtaining PEG-based coatings on different families of NPs, we also obtained multifunctional coatings by incorporating fluorescein functionalities. The resulting coatings not only confer biocompatibility and excellent cell internalization, but also allow for the imaging and tracking of NPs within cells. Full article

We describe the antioxidant capability of scavenging the superoxide radical of several tea and yerba mate samples using rotating ring–disk electrochemistry (RRDE). We directly measured superoxide concentrations and detected their decrease upon the addition of an antioxidant to the electrochemical cell. We studied two varieties of yerba mate, two varieties of black tea from Bangladesh, a sample of Pu-erh tea from China, and two components, caffeic acid and chlorogenic acid. All of these plant infusions and components showed strong antioxidant activities, virtually annihilating the available superoxide concentration. Using density functional theory (DFT) calculations, we describe a mechanism of superoxide scavenging via caffeic and chlorogenic acids. Superoxide can initially interact at two sites in these acids: the H4 catechol hydrogen (a) or the acidic proton of the acid (b). For (a), caffeic acid needs an additional π–π superoxide radical, which transfers electron density to the ring and forms a HO₂⁻ anion. A second caffeic acid proton and HO₂⁻ anion forms H₂O₂. Chlorogenic acid acts differently, as the initial approach of superoxide to the catechol moiety (a) is enough to form the HO₂⁻ anion. After an additional acidic proton of chlorogenic acid is given to HO₂⁻, three well-separated compounds arise: (1) a carboxylate moiety, (2) H₂O₂, and a (3) chlorogenic acid semiquinone. The latter can capture a second superoxide in a π–π manner, which remains trapped due to the aromatic ring, as for caffeic acid. With enough of both acids and superoxide radicals, the final products are equivalent: H₂O₂ plus a complex of the type [X-acid–η–O₂], X = caffeic, chlorogenic. Chlorogenic acid (b) is described by the following reaction: 2 O₂^•− + 2 chlorogenic acid → 2 chlorogenic carboxylate + O₂ + H₂O₂, and so, it acts as a non-enzymatic superoxide dismutase (SOD) mimic, as shown via the product formation of O₂ plus H₂O₂, which is limited due to chlorogenic acid consumption. Caffeic acid (b) differs from chlorogenic acid, as there is no acidic proton capture via superoxide. In this case, approaching a second superoxide to the H4 polyphenol moiety forms a HO₂⁻ anion and, later, an H₂O₂ molecule upon the transfer of a second caffeic acid proton. Full article

Background: Electrodeposition of functional films from polyphenol-containing solutions has emerged as a new field of surface functionalization from bio-sourced molecules. There is, however, almost no knowledge about the chemical structure of such complex films. It is the aim of this research to use the known electrodeposition of films made from catechol and resorcinol, two isomers of dihydroxybenzene, to understand the electrodeposition of a more complex polyphenol, quercetin, which is constituted from a fused catechol and resorcinol moiety. The aim of this article is hence to introduce some methodology in the interpretation of the electrochemical behavior of complex polyphenols starting from their building blocks. Methods: Cyclic voltammetry (CV) is used to deposit films from quercetin and from equimolar blends of catechol and resorcinol on amorphous carbon and gold working electrodes. The main experimental parameter was the potential sweep rate used during the CVs. Results: The CV of quercetin is not the exact sum of the CV of the catechol + resorcinol blends, but the major features are conserved, namely the presence of two main oxidation peaks affiliated to those of catechol and resorcinol but shifted to less anodic potentials. In addition, the anodic electron transfer coefficients of the two oxidation waves of quercetin are higher than those measured in the catechol resorcinol blend. However, film deposition ability is reduced with quercetin compared to catechol + resorcinol blend in probable relationship to steric hindrance occurring during the non-electrochemical crosslinking of the deposit. The quercetin-based films deposited at 10 mV·s⁻¹ on gold electrodes are conformal and display some antioxidant activity. Full article

A series of novel organogermanium(IV) catecholates 1–9 of the general formula R’₂Ge(Cat), where R’ = Ph, Et, have been synthesized. Compounds were characterized by ¹H, ¹³C NMR, IR spectroscopy, and elemental analysis. The molecular structures of 1–3, 6, and 8 in crystal state were established using single-crystal X-ray analysis. The complexes are tetracoordinate germanium(IV) compounds containing a dioxolene ligand in a dianion (catecholato) form. Electrochemical transformations of target germanium(IV) complexes have been studied by cyclic voltammetry. The electro-oxidation mechanism of complexes 1–5, 7, and 10 (the related complex Ph₂Ge(3,5-Cat) where 3,5-Cat is 3,5-di-tert-butylcatecholate) involves the consecutive formation of mono- and dicationic derivatives containing the oxidized forms of redox-active ligands. The stability of the generated monocations depends both on the hydrocarbon groups at the germanium atom and on the substituents in the catecholate ring. Compounds 6, 8, and 9 are oxidized irreversibly under the electrochemical conditions with the formation of unstable complexes. The radical scavenging activity and antioxidant properties of new complexes were estimated in the reaction with DPPH radical, ABTS radical cation, and CUPRAC_TEAC assay. It has been found that compounds 8 and 9 with benzothiazole or phenol fragments are more active in DPPH test. The presence of electron-rich moieties in the catecholate ligand makes complexes 5 and 7–9 more reactive to ABTS radical cation. The value of CUPRAC_TEAC for organogermanium(IV) catecholates varies from 0.23 to 1.45. The effect of compounds 1–9 in the process of lipid peroxidation of rat liver (Wistar) homogenate was determined in vitro. It was found that most compounds are characterized by pronounced antioxidant activity. A feature of complexes 1, 3, and 5–9 is the intensification of the antioxidant action with the incubation time. In the presence of additives of complexes 3, 5, 6, and 8, an induction period was observed during the process of lipid peroxidation. Full article

Phosphodiesterase 4 (PDE4) enzymes catalyze cyclic adenosine monophosphate (cAMP) hydrolysis and are involved in a variety of physiological processes, including brain function, monocyte and macrophage activation, and neutrophil infiltration. Among different PDE4 isoforms, Phosphodiesterases 4D (PDE4Ds) play a fundamental role in cognitive, learning and memory consolidation processes and cancer development. Selective PDE4D inhibitors (PDE4Dis) could represent an innovative and valid therapeutic strategy for the treatment of various neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, Huntington’s, and Lou Gehrig’s diseases, but also for stroke, traumatic brain and spinal cord injury, mild cognitive impairment, and all demyelinating diseases such as multiple sclerosis. In addition, small molecules able to block PDE4D isoforms have been recently studied for the treatment of specific cancer types, particularly hepatocellular carcinoma and breast cancer. This review overviews the PDE4DIsso far identified and provides useful information, from a medicinal chemistry point of view, for the development of a novel series of compounds with improved pharmacological properties. Full article