Study on methane degradation by microbial agents based on chelating wetting agent carriers.

Due to the low permeability characteristics of the deep gas-containing coal seam, the conventional prevention and control measures that cannot solve the problems of gas outbursts are unsatisfactory for the prevention and control of the coal and gas outbursts disaster. Therefore, in this study, a strain of methane-oxidizing bacteria M07 with high-pressure resistance, strong resistance, and high methane degradation rate was selected from coal mines. The growth and degradation abilities of M07 in chelating wetting agent solutions to assess its adaptability and find the optimal agent-to-M07 ratio. It provides a new method for integrating the reduction of impact tendency and gas pressure in deep coal mines. The experimental results show that M07 is a Gram-positive bacterium of the genus Bacillus, which has strong resistance and adaptability to high-pressure water injection. By degrading 70 mol of methane, M07 produces 1 mol of carbon dioxide, which can reduce gas pressure and reduce the risk of gas outbursts in coal mines. As the experiment proves, the best effect was achieved when the M07 concentration of the chelating wetting agent was 0.05%. The methane-oxidizing bacteria based on the chelating wetting agent as carriers prove a new prevention and control method for the integrated prevention and control of coal and gas outbursts in coal mines and also provide a new idea for microbial application in coal mine disaster control.

Aquatic assessment of the chelating ability of Silica-stabilized magnetite nanocomposite to lead nitrate toxicity with emphasis to their impact on hepatorenal, oxidative stress, genotoxicity, histopathological, and bioaccumulation parameters in Oreochromis niloticus and Clarias gariepinus.

BACKGROUND: In recent years, anthropogenic activities have released heavy metals and polluted the aquatic environment. This study investigated the ability of the silica-stabilized magnetite (Si-M) nanocomposite materials to dispose of lead nitrate (Pb(NO3)2) toxicity in Nile tilapia and African catfish. RESULTS: Preliminary toxicity tests were conducted and determined the median lethal concentration (LC50) of lead nitrate (Pb(NO3)2) to Nile tilapia and African catfish to be 5 mg/l. The sublethal concentration, equivalent to 1/20 of the 96-hour LC50 Pb(NO3)2, was selected for our experiment. Fish of each species were divided into four duplicated groups. The first group served as the control negative group, while the second group (Pb group) was exposed to 0.25 mg/l Pb(NO3)2 (1/20 of the 96-hour LC50). The third group (Si-MNPs) was exposed to silica-stabilized magnetite nanoparticles at a concentration of 1 mg/l, and the fourth group (Pb + Si-MNPs) was exposed simultaneously to Pb(NO3)2 and Si-MNPs at the same concentrations as the second and third groups. Throughout the experimental period, no mortalities or abnormal clinical observations were recorded in any of the treated groups, except for melanosis and abnormal nervous behavior observed in some fish in the Pb group. After three weeks of sublethal exposure, we analyzed hepatorenal indices, oxidative stress parameters, and genotoxicity. Values of alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), urea, and creatinine were significantly higher in the Pb-intoxicated groups compared to the control and Pb + Si-MNPs groups in both fish species. Oxidative stress parameters showed a significant decrease in reduced glutathione (GSH) concentration, along with a significant increase in malondialdehyde (MDA) and protein carbonyl content (PCC) concentrations, as well as DNA fragmentation percentage in the Pb group. However, these values were nearly restored to control levels in the Pb + Si-MNPs groups. High lead accumulation was observed in the liver and gills of the Pb group, with the least accumulation in the muscles of tilapia and catfish in the Pb + Si-MNPs group. Histopathological analysis of tissue samples from Pb-exposed groups of tilapia and catfish revealed brain vacuolation, gill fusion, hyperplasia, and marked hepatocellular and renal necrosis, contrasting with Pb + Si-MNP group, which appeared to have an apparently normal tissue structure. CONCLUSIONS: Our results demonstrate that Si-MNPs are safe and effective aqueous additives in reducing the toxic effects of Pb (NO3)2 on fish tissue through the lead-chelating ability of Si-MNPs in water before being absorbed by fish.

Copper Chelation Therapy Attenuates Periodontitis Inflammation through the Cuproptosis/Autophagy/Lysosome Axis.

Periodontitis development arises from the intricate interplay between bacterial biofilms and the host's immune response, where macrophages serve pivotal roles in defense and tissue homeostasis. Here, we uncover the mitigative effect of copper chelator Tetrathiomolybdate (TTM) on periodontitis through inhibiting cuproptosis, a newly identified form of cell death which is dependent on copper. Our study reveals concurrent cuproptosis and a macrophage marker within murine models. In response to lipopolysaccharide (LPS) stimulation, macrophages exhibit elevated cuproptosis-associated markers, which are mitigated by the administration of TTM. TTM treatment enhances autophagosome expression and mitophagy-related gene expression, countering the LPS-induced inhibition of autophagy flux. TTM also attenuates the LPS-induced fusion of autophagosomes and lysosomes, the degradation of lysosomal acidic environments, lysosomal membrane permeability increase, and cathepsin B secretion. In mice with periodontitis, TTM reduces cuproptosis, enhances autophagy flux, and decreases Ctsb levels. Our findings underscore the crucial role of copper-chelating agent TTM in regulating the cuproptosis/mitophagy/lysosome pathway during periodontitis inflammation, suggesting TTM as a promising approach to alleviate macrophage dysfunction. Modulating cuproptosis through TTM treatment holds potential for periodontitis intervention.

Targeting Biometals in Alzheimer's Disease with Metal Chelating Agents Including Coumarin Derivatives.

Numerous physiological processes happening in the human body, including cerebral development and function, require the participation of biometal ions such as iron, copper, and zinc. Their dyshomeostasis may, however, contribute to the onset of Alzheimer's disease (AD) and potentially other neurodegenerative diseases. Chelation of biometal ions is therefore a therapeutic strategy against AD. This review provides a survey of natural and synthetic chelating agents that are or could potentially be used to target the metal hypothesis of AD. Since metal dyshomeostasis is not the only pathological aspect of AD, and the nature of this disorder is very complex and multifactiorial, the most efficient therapeutics should target as many neurotoxic factors as possible. Various coumarin derivatives match this description and apart from being able to chelate metal ions, they exhibit the capacity to inhibit cholinesterases (ChEs) and monoamine oxidase B (MAO-B) while also possessing antioxidant, anti-inflammatory, and numerous other beneficial effects. Compounds based on the coumarin scaffold therefore represent a desirable class of anti-AD therapeutics.

Copper-Based Complexes with Adamantane Ring-Conjugated bis(3,5-Dimethyl-pyrazol-1-yl)acetate Ligand as Promising Agents for the Treatment of Glioblastoma.

The new ligand L2Ad, obtained by conjugating the bifunctional species bis(3,5-dimethylpyrazol-1-yl)-acetate and the drug amantadine, was used as a chelator for the synthesis of new Cu complexes 1-5. Their structures were investigated by synchrotron radiation-induced X-ray photoelectron spectroscopy (SR-XPS), near-edge X-ray absorption fine structure (NEXAFS) spectroscopy, and by combining X-ray absorption fine structure (XAFS) spectroscopy techniques and DFT modeling. The structure of complex 3 was determined by single-crystal X-ray diffraction analysis. Tested on U87, T98, and U251 glioma cells, Cu(II) complex 3 and Cu(I) complex 5 decreased cell viability with IC50 values significantly lower than cisplatin, affecting cell growth, proliferation, and death. Their effects were prevented by treatment with the Cu chelator tetrathiomolybdate, suggesting the involvement of copper in their cytotoxic activity. Both complexes were able to increase ROS production, leading to DNA damage and death. Interestingly, nontoxic doses of 3 or 5 enhanced the chemosensitivity to Temozolomide.

Power of Dopamine: Multifunctional Compound Assisted Conversion of the Most Risk Factor into Therapeutics of Alzheimer's Disease.

In Alzheimer's disease (AD), reactive oxygen species (ROS) plays a crucial role, which is produced from molecular oxygen with extracellular deposited amyloid-ß (Aß) aggregates through the reduction of a Cu2+ ion. In the presence of a small amount of redox-active Cu2+ ion, ROS is produced by the Aß-Cu2+ complex as Aß peptide alone is unable to generate excess ROS. Therefore, Cu2+ ion chelators are considered promising therapeutics against AD. Here, we have designed and synthesized a series of Schiff base derivatives (SB) based on 2-hydroxy aromatic aldehyde derivatives and dopamine. These SB compounds contain one copper chelating core, which captures the Cu2+ ions from the Aß-Cu2+ complex. Thereby, it inhibits copper-induced amyloid aggregation as well as amyloid self-aggregation. It also inhibits copper-catalyzed ROS production through sequestering of Cu2+ ions. The uniqueness of our designed ligands has the dual property of dopamine, which not only acts as a ROS scavenger but also chelates the copper ion. The crystallographic analysis proves the power of the dopamine unit. Therefore, dual exploration of dopamine core can be considered as potential therapeutics for future AD treatment.

Customizable Zr-MOF nanoantidote-based multieffective arsenic detoxification and its extended low-toxic therapy.

Arsenic (As) poisoning has become a global public problem threatening human health. Chelation therapy (CT) is the preferred treatment for arsenic poisoning. Nevertheless, efficient and safe arsenic removal in vivo remains a daunting challenge due to the limitations of chelators, including weak affinity, poor cell membrane penetration, and short half-life. Herein, a mercapto-functionalized and size-tunable hierarchical porous Zr-MOF (UiO-66-TC-SH) is developed, which possesses abundant arsenic chemisorption sites, effective cell uptake ability, and long half-life, thereby efficiently removing toxic arsenic in vivo. Moreover, the strong binding affinity of UiO-66-TC-SH for arsenic reduces systemic toxicity caused by off-target effects. In animal trials, UiO-66-TC-SH decreases the blood arsenic levels of acute arsenic poisoning mice to a normal value within 48 h, and the efficacy is superior to clinical drugs 2,3-dimercaptopropanesulfonic acid sodium salt (DMPS). Meanwhile, UiO-66-TC-SH also significantly mitigates the arsenic accumulation in the metabolic organs of chronic arsenic poisoning mice. Surprisingly, UiO-66-TC-SH also accelerates the metabolism of arsenic in organs of tumor-bearing mice and alleviates the side effects of arsenic drugs antitumor therapy. STATEMENT OF SIGNIFICANCE: Arsenic (As) contamination has become a global problem threatening public health. The present clinical chelation therapy (CT) still has some limitations, including the weak affinity, poor cell membrane permeability and short half-life of hydrophilic chelators. Herein, a metal-organic framework (MOF)-based multieffective arsenic removal strategy in vivo is proposed for the first time. Mercapto-functionalized and size-tunable hierarchical porous Zr-MOF nanoantidote (denoted as UiO-66-TC-SH) is accordingly designed and synthesized. After injection, UiO-66-TC-SH can form Zr-O-As bonds and As-S bonds with arsenic, thus enhancing arsenic adsorption capacity, cycling stability and systemic safety simultaneously. The acute arsenic poisoning model results indicate that UiO-66-TC-SH shows superior efficacy to the clinical drug sodium dimercaptopropanesulfonate (DMPS). More meaningfully, we find that UiO-66-TC-SH also accelerates the metabolism of arsenic in organs of tumor-bearing mice and alleviates side effects of arsenic drugs anti-tumor therapy.

5,7-dihydroxy-3',4',5'-trimethoxyflavone mitigates lead induced neurotoxicity in rats via its chelating, antioxidant, anti-inflammatory and monoaminergic properties.

Chronic exposure to lead (Pb) induces neurodegenerative changes in animals and humans. Drugs with strong antioxidant properties are effective against Pb-mediated neurotoxicity. In a prior study, we identified 5,7-dihydroxy-3',4',5'-trimethoxyflavone (TMF) from Ocimum basilicum L. leaves as a potent antioxidant and neuroprotective compound. This research explores TMF's neuroprotective effects against Pb-induced brain toxicity in rats to establish it as a therapeutic agent. Rats received lead acetate (100 mg/kg, orally, once daily) for 30 days to induce brain injury, followed by TMF treatment (5 and 10 mg/kg, oral, once daily) 30 min later. Cognitive and motor functions were assessed using Morris Water Maze and horizontal bar tests. Lead, monoamine oxidase (MAO) A and B enzymes, reduced glutathione (GSH), thiobarbituric acid reactive species (TBARS), Tumor necrosis factor-alpha (TNF-α), and IL-6 levels were measured in the hippocampus and cerebellum. Pb exposure impaired cognitive and motor functions, increased Pb, TBARS, TNF-α, and IL-6 levels, and compromised MAO A & B and GSH levels. TMF reversed Pb-induced memory and motor deficits and normalized biochemical anomalies. TMF's neuroprotective effects against lead involve chelating, antioxidant, anti-inflammatory, and monoaminergic properties, suggesting its potential as a treatment for metal-induced brain injury.

Comparative effects of 17% ethylenediaminetetraacetic acid and 9% etidronic acid applied with different irrigant activation techniques on the release of growth factors from dentin: in vitro study.

BACKGROUND: Growth factors embedded in the extracellular matrix of the dentin play an important role in the migration, proliferation, and differentiation of dental pulp stem cells in regenerative endodontics. In regenerative endodontic treatments, the type of irrigation solution used is crucial for the release of growth factors (GFs) from the dentin matrix. This study evaluated the effectiveness of different irrigant activation techniques (IAT) using two different chelating agents, 17% ethylenediaminetetraacetic acid (EDTA) and 9% etidronic acid (HEDP), in terms of their GF release. METHODS: Seventy-two mandibular premolar teeth were prepared to simulate an open apex. The root fragments were irrigated with 20 ml of 1.5% sodium hypochlorite and 20 ml of saline solution. Eight root fragments were randomly separated for the control group, and the remaining 64 fragments were randomly separated into eight groups based on two different chelating agents (17% EDTA and 9% HEDP) and four different IAT ((conventional needle irrigation (CNI), passive ultrasonic irrigation (PUI), sonic activation with EDDY, and XP-endo Finisher (XPF)). TGF-ß1, VEGF-A, BMP-7 and IGF-1 release levels were determined using an ELISA, and statistical analysis was performed using the Kolmogorov-Smirnov test, ANOVA, and the Tukey test (p < .05). RESULTS: Compared to the control group, the experimental groups showed significantly higher GF release when using EDTA or HEDP. Among the activation groups, the EDDY group triggered the highest GF release, and the CNI group triggered the lowest. CONCLUSIONS: IAT with EDTA and HEDP can increase GF release, with EDDY being the most effective IAT method. Using chelating agents with IAT may be beneficial in regenerative endodontic treatments.

Enhancing antibacterial properties by regulating valence configurations of copper: a focus on Cu-carboxyl chelates.

Optimizing the antibacterial effectiveness of copper ions while reducing environmental and cellular toxicity is essential for public health. A copper chelate, named PAI-Cu, is skillfully created using a specially designed carboxyl copolymer (a combination of acrylic and itaconic acids) with copper ions. PAI-Cu demonstrates a broad-spectrum antibacterial capability both in vitro and in vivo, without causing obvious cytotoxic effects. When compared to free copper ions, PAI-Cu displays markedly enhanced antibacterial potency, being about 35 times more effective against Escherichia coli and 16 times more effective against Staphylococcus aureus. Moreover, Gaussian and ab initio molecular dynamics (AIMD) analyses reveal that Cu+ ions can remain stable in the carboxyl compound's aqueous environment. Thus, the superior antibacterial performance of PAI-Cu largely stems from its modulation of copper ions between mono- and divalent states within the Cu-carboxyl chelates, especially via the carboxyl ligand. This modulation leads to the generation of reactive oxygen species (˙OH), which is pivotal in bacterial eradication. This research offers a cost-effective strategy for amplifying the antibacterial properties of Cu ions, paving new paths for utilizing copper ions in advanced antibacterial applications.

One-step high efficiency separation of prolyl endopeptidase from Aspergillus niger and its application.

Prolyl endopeptidase from Aspergillus niger (An-PEP) is an enzyme that recognizes C-terminal peptide bonds of amino acid chains and cleaves them by hydrolysis. An aqueous two-phase system (ATPS) was used to separate An-PEP from fermentation broth. Through single factor experiments, the ATPS containing 16 % (w/w) PEG2000 and 15 % (w/w) (NH4)2SO4 at pH 6.0 obtained the recovery of 79.74 ± 0.16 % and the purification coefficient of 7.64 ± 0.08. It was then used to produce soy protein isolate peptide (SPIP) by hydrolysis of soy protein isolate (SPI), and SPIP-Ferrous chelate (SPIP-Fe) was prepared with SPIP and Fe2+. The chelation conditions were optimized by RSM, as the chelation time was 30 min, chelation temperature was 25 °C, SPIP mass to VC mass was two to one and pH was 6.0. The obtained chelation rate was 82.56 ± 2.30 %. The change in the structures and functional features of SPIP before and after chelation were investigated. The FTIR and UV-Vis results indicated that the chelation of Fe2+ and SPIP depended mainly on the formation of amide bonds. The fluorescence, SEM and amino acid composition analysis results indicated that Fe2+ could induce and stabilize the surface conformation and change the amino acid distribution on the surfaces of SPIP. The chelation of SPIP and Fe2+ resulted in the enhancement of radical scavenging activities and ACE inhibitory activities. This work provided a new perspective for the further development of peptide-Fe chelates for iron supplement.

A Copper-Selective Sensor and Its Inhibition of Copper-Amyloid Beta Aggregation.

Copper is an essential trace metal for biological processes in humans and animals. A low level of copper detection at physiological pH using fluorescent probes is very important for in vitro applications, such as the detection of copper in water or urine, and in vivo applications, such as tracking the dynamic copper concentrations inside cells. Copper homeostasis is disrupted in neurological diseases like Alzheimer's disease, and copper forms aggregates with amyloid beta (Ab42) peptide, resulting in senile plaques in Alzheimer's brains. Therefore, a selective copper detector probe that can detect amyloid beta peptide-copper aggregates and decrease the aggregate size has potential uses in medicine. We have developed a series of Cu2+-selective low fluorescent to high fluorescent tri and tetradentate dentate ligands and conjugated them with a peptide ligand to amyloid-beta binding peptide to increase the solubility of the compounds and make the resultant compounds bind to Cu2+-amyloid aggregates. The copper selective compounds were developed using chemical scaffolds known to have high affinity and selectivity for Cu2+, and their conjugates with peptides were tested for affinity and selectivity towards Cu2+. The test results were used to inform further improvement of the next compound. The final Cu2+ chelator-peptide conjugate we developed showed high selectivity for Cu2+ and high fluorescence properties. The compound bound 1:1 to Cu2+ ion, as determined from its Job's plot. Fluorescence of the ligand could be detected at nanomolar concentrations. The effect of this ligand on controlling Cu2+-Ab42 aggregation was studied using fluorescence assays and microscopy. It was found that the Cu2+-chelator-peptide conjugate efficiently reduced aggregate size and, therefore, acted as an inhibitor of Ab42-Cu2+ aggregation. Since high micromolar concentrations of Cu2+ are present in senile plaques, and Cu2+ accelerates the formation of toxic soluble aggregates of Ab42, which are precursors of insoluble plaques, the developed hybrid molecule can potentially serve as a therapeutic for Alzheimer's disease.

Trapping mechanism by di-d-psicose anhydride with methylglyoxal for prevention of diabetic nephropathy.

Di-d-psicose anhydride (DPA), derived from functional rare saccharide as d-psicose, is investigated for its strong chelating ability. Methylglyoxal (MGO), an important precursor of advanced glycation end-products (AGEs), promotes obesity, and causes complications such as diabetic nephropathy. On mesangial cells, DPA can substantially reduce the negative effects of MGO. DPA effectively trapping MGO in mesangial cells. The bonding properties of the DPA-MGO adduct were discussed by mass spectrometry and nuclear magnetic resonance (NMR). The NMR spectra of the DPA-MGO adduct provide evidence for chelation bonding. The inhibition of AGE formation and the mass spectrometry results of the DPA-MGO adduct indicate that DPA can scavenge MGO at a molar ratio of 1:1. DPA suppressed 330 % of the up-regulated receptor for an AGEs protein expression to a normal level and restored the suppressed glyoxalase 1 level to 86 % of the normal group. This research provides important evidence and theoretical basis for the development of AGE inhibitors derived from rare saccharide.

Dendritic Pyridine-Imine Copper Complexes as Metallo-Drugs.

Since the discovery of cisplatin in the 1960s, the search for metallo-drugs that are more efficient than platinum complexes with negligible side effects has attracted much interest. Among the other metals that have been examined for potential applications as anticancer agents is copper. The interest in copper was recently boosted by the discovery of cuproptosis, a recently evidenced form of cell death mediated by copper. However, copper is also known to induce the proliferation of cancer cells. In view of these contradictory results, there is a need to find the most suitable copper chelators, among which Schiff-based derivatives offer a wide range of possibilities. Gathering several metal complexes in a single, larger entity may provide enhanced properties. Among the nanometric objects suitable for such purpose are dendrimers, precisely engineered hyperbranched macromolecules, which are outstanding candidates for improving therapy and diagnosis. In this review article, we present an overview of the use of a particular Schiff base, namely pyridine-imine, linked to the surface of dendrimers, suitable for complexing copper, and the use of such dendrimer complexes in biology, in particular against cancers.

Zinc-chelating BET bromodomain inhibitors equally target islet endocrine cell types.

Inhibition of the bromodomain and extraterminal domain (BET) protein family is a potential strategy to prevent and treat diabetes; however, the clinical use of BET bromodomain inhibitors (BETis) is associated with adverse effects. Here, we explore a strategy for targeting BETis to ß cells by exploiting the high-zinc (Zn2+) concentration in ß cells relative to other cell types. We report the synthesis of a novel, Zn2+-chelating derivative of the pan-BETi (+)-JQ1, (+)-JQ1-DPA, in which (+)-JQ1 was conjugated to dipicolyl amine (DPA). As controls, we synthesized (+)-JQ1-DBA, a non-Zn2+-chelating derivative, and (-)-JQ1-DPA, an inactive enantiomer that chelates Zn2+. Molecular modeling and biophysical assays showed that (+)-JQ1-DPA and (+)-JQ1-DBA retain potent binding to BET bromodomains in vitro. Cellular assays demonstrated (+)-JQ1-DPA attenuated NF-ĸB target gene expression in ß cells stimulated with the proinflammatory cytokine interleukin 1ß. To assess ß-cell selectivity, we isolated islets from a mouse model that expresses green fluorescent protein in insulin-positive ß cells and mTomato in insulin-negative cells (non-ß cells). Surprisingly, Zn2+ chelation did not confer ß-cell selectivity as (+)-JQ1-DPA was equally effective in both ß and α cells; however, (+)-JQ1-DPA was less effective in macrophages, a nonendocrine islet cell type. Intriguingly, the non-Zn2+-chelating derivative (+)-JQ1-DBA displayed the opposite selectivity, with greater effect in macrophages compared with (+)-JQ1-DPA, suggesting potential as a macrophage-targeting molecule. These findings suggest that Zn2+-chelating small molecules confer endocrine cell selectivity rather than ß-cell selectivity in pancreatic islets and provide valuable insights and techniques to assess Zn2+ chelation as an approach to selectively target small molecules to pancreatic ß cells.NEW & NOTEWORTHY Inhibition of BET bromodomains is a novel potential strategy to prevent and treat diabetes mellitus. However, BET inhibitors have negative side effects. We synthesized a BET inhibitor expected to exploit the high zinc concentration in ß cells to accumulate in ß cells. We show our inhibitor targeted pancreatic endocrine cells; however, it was less effective in immune cells. A control inhibitor showed the opposite effect. These findings help us understand how to target specific cells in diabetes treatment.

Polymeric Nanozyme with SOD Activity Capable of Inhibiting Self- and Metal-Induced α-Synuclein Aggregation.

Despite decades of research, Parkinson's disease is still an idiopathic pathology for which no cure has yet been found. This is partly explained by the multifactorial character of most neurodegenerative syndromes, whose generation involves multiple pathogenic factors. In Parkinson's disease, two of the most important ones are the aggregation of α-synuclein and oxidative stress. In this work, we address both issues by synthesizing a multifunctional nanozyme based on grafting a pyridinophane ligand that can strongly coordinate CuII, onto biodegradable PEGylated polyester nanoparticles. The resulting nanozyme exhibits remarkable superoxide dismutase activity together with the ability to inhibit the self-induced aggregation of α-synuclein into amyloid-type fibrils. Furthermore, the combination of the chelator and the polymer produces a cooperative effect whereby the resulting nanozyme can also halve CuII-induced α-synuclein aggregation.

Promoting the Anticancer Activity with Multidentate Furan-2-Carboxamide Functionalized Aroyl Thiourea Chelation in Binuclear Half-Sandwich Ruthenium(II) Complexes.

A new set of binuclear arene ruthenium complexes [Ru2(p-cymene)2(k4-N2OS)(L1-L3)Cl2] (Ru2L1-Ru2L3) encompassing furan-2-carboxamide-based aroylthiourea derivatives (H2L1-H2L3) was synthesized and characterized by various spectral and analytical techniques. Single-crystal XRD analysis unveils the N^O and N^S mixed monobasic bidentate coordination of the ligands constructing N, S, Cl/N, O, and Cl legged piano stool octahedral geometry. DFT analysis demonstrates the predilection for the formation of stable arene ruthenium complexes. In vitro antiproliferative activity of the complexes was examined against human cervical (HeLa), breast (MCF-7), and lung (A549) cancerous and noncancerous monkey kidney epithelial (Vero) cells. All the complexes are more efficacious against HeLa and MCF-7 cells with low inhibitory doses (3.86-11.02 µM). Specifically, Ru2L3 incorporating p-cymene and -OCH3 fragments exhibits high lipophilicity, significant cytotoxicity against cancer cells, and lower toxicity on noncancerous cells. Staining analysis indicates the apoptosis-associated cell morphological changes expressively in MCF-7 cells. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) analyses reveal that Ru2L3 can raise ROS levels, reduce MMP, and trigger mitochondrial dysfunction-mediated apoptosis. The catalytic oxidation of glutathione (GSH) to its disulfide form (GSSG) by the complexes may simultaneously increase the ROS levels, alluding to their observed cytotoxicity and apoptosis induction. Flow cytometry determined the quantitative classification of late apoptosis and S-phase arrest in MCF-7 and HeLa cells. Western blotting analysis confirmed that the complexes promote apoptosis by upregulating Caspase-3 and Caspase-9 and downregulating BCL-2. Molecular docking studies unfolded the strong binding affinities of the complexes with VEGFR2, an angiogenic signaling receptor, and BCL2, Cyclin D1, and HER2 proteins typically overexpressed on tumor cells.

Cinnamic Acid: A Low-Toxicity Natural Bidentate Ligand for Uranium Decorporation.

Uranium accumulation in the kidneys and bones following internal contamination results in severe damage, emphasizing the pressing need for the discovery of actinide decorporation agents with efficient removal of uranium and low toxicity. In this work, cinnamic acid (3-phenyl-2-propenoic acid, CD), a natural aromatic carboxylic acid, is investigated as a potential uranium decorporation ligand. CD demonstrates markedly lower cytotoxicity than that of diethylenetriaminepentaacetic acid (DTPA), an actinide decorporation agent approved by the FDA, and effectively removes approximately 44.5% of uranyl from NRK-52E cells. More importantly, the results of the prompt administration of the CD solution remove 48.2 and 27.3% of uranyl from the kidneys and femurs of mice, respectively. Assessments of serum renal function reveal the potential of CD to ameliorate uranyl-induced renal injury. Furthermore, the single crystal of CD and uranyl compound (C9H7O2)2·UO2 (denoted as UO2-CD) reveals the formation of uranyl dimers as secondary building units. Thermodynamic analysis of the solution shows that CD coordinates with uranyl to form a 2:1 molar ratio complex at a physiological pH of 7.4. Density functional theory (DFT) calculations further show that CD exhibits a significant 7-fold heightened affinity for uranyl binding in comparison to DTPA.

Extraction of heavy metals from copper tailings by ryegrass (Lolium perenne L.) with the assistance of degradable chelating agents.

Heavy metal contamination is an urgent ecological governance problem in mining areas. In order to seek for a green and environmentally friendly reagent with better plant restoration effect to solve the problem of low efficiency in plant restoration in heavy metal pollution soil. In this study, we evaluated the effects of three biodegradable chelating agents, namely citric acid (CA), fulvic acid (FA) and polyaspartic acid (PASP), on the physicochemical properties of copper tailings, growth of ryegrass (Lolium perenne L.) and heavy metal accumulation therein. The results showed that the chelating agent application improved the physicochemical properties of copper tailings, increased the biomass of ryegrass and enriched more Cu and Cd in copper tailings. In the control group, the main existing forms of Cu and Cd were oxidizable state, followed by residual, weak acid soluble and reducible states. After the CA, FA or PASP application, Cu and Cd were converted from the residual and oxidizable states to the reducible and weak acid soluble states, whose bioavailability in copper tailings were thus enhanced. Besides, the chelating agent incorporation improved the Cu and Cd extraction efficiencies of ryegrass from copper tailings, as manifested by increased root and stem contents of Cu and Cd by 30.29-103.42%, 11.43-74.29%, 2.98-110.98% and 11.11-111.11%, respectively, in comparison with the control group. In the presence of multiple heavy metals, CA, FA or PASP showed selectivity regarding the ryegrass extraction of heavy metals from copper tailings. PCA analysis revealed that the CA-4 and PASP-7 treatment had great remediation potentials against Cu and Cd in copper tailings, respectively, as manifested by increases in Cu and Cd contents in ryegrass by 90.98% and 74.29% compared to the CK group.

Coordination environment dependence of anticancer activity in cyclometalated bismuth(III) complexes with C,O-chelating ligands.

In this paper, a series of cyclometalated bismuth(III) complexes bearing C,O-bidentate ligands were synthesized and characterized by techniques such as UV-vis, NMR, HRMS, and single crystal X-ray diffraction. Meanwhile, their cytotoxicities against various human cell lines, including colon cancer cells (HCT-116), breast cancer cells (MDA-MB-231), lung cancer cells (A549), gastric cancer cells (SGC-7901), and normal embryonic kidney cells (HEK-293) were assessed in vitro. Compared with the clinical cisplatin, most of the synthesized complexes possessed significantly higher degrees of anticancer activity and selectivity, giving a selectivity index of up to 71.3. The structure-activity relationship study revealed that the anticancer performance of these bismuth(III) species depends on the factors of coordination environment surrounding the metal center, such as coordination number, coordination bonding strength, lone 6s2 electron pair stereoactivity. The Annexin V-FITC/PI double staining assay results suggested that the coordination environment-dependent cytotoxicity is ascribable to apoptosis. Western blot analysis confirmed the proposal, as evidenced by the down-regulating level of Bcl-2 and the activation of caspase-3. Furthermore, the representative complexes Bi1, Bi4, Bi6, and Bi8 exhibited relatively lower inhibitory efficiency on human ovarian cancer cells (A2780) than on its cisplatin-resistant daughter cells (A2780/cis), thus demonstrating that such compounds are capable of circumventing the cisplatin-induced resistance. This investigation elucidated the excellent anticancer performance of C,O-coordinated bismuth(III) complexes and established the correlation between cytotoxic activity and coordination chemistry, which provides a practical basis for in-depth designing and developing bismuth-based chemotherapeutics.