Excellent Binding Affinity Research Articles

Computational Analysis of Bacopa monnieri (L.) Wettst. Compounds for Drug Development against Neurodegenerative Disorders.

With several experimental studies establishing the role of Bacopa monnieri as an effective neurological medication, less focus has been employed to explore how effectively Bacopa monnieri brings about this property. The current work focuses on understanding the molecular interaction of the phytochemicals of the plant against different neurotrophic factors to explore their role and potential as potent anti-neurodegenerative drugs. Neurotrophins play a crucial role in the development and regulation of neurons. Alterations in the functioning of these Neurotrophins lead to several Neurodegenerative Disorders. Albeit engineered medications are accessible for the treatment of Neurodegenerative Disorders, due to their numerous side effects, it becomes imperative to formulate and synthesize novel drug candidates. This study aims to investigate the potential of Bacopa monnieri phytochemicals as potent antineurodegenerative drugs by inspecting the interactions between Neurotrophins and target proteins. The current study employs molecular docking and molecular dynamic simulation studies to examine the molecular interactions of phytochemicals with respective Neurotrophins. Further inspection of the screened phytochemicals was performed to analyze the ADME-Tox properties in order to classify the screened phytochemicals as potent drug candidates. The phytochemicals of Bacopa monnieri were subjected to in-silico docking with the respective Neurotrophins. Vitamin E, Benzene propanoic acid, 3,5-bis (1,1- dimethylethyl)- 4hydroxy-, methyl ester (BPA), Stigmasterol, and Nonacosane showed an excellent binding affinity with their respective Neurotrophins (BDNF, NT3, NT4, NGF). Moreover, the molecular dynamic simulation studies revealed that BPA and Stigmasterol show a very stable interaction with NT3 and NT4, respectively, suggesting their potential role as a drug candidate. Nonacosane exhibited a fluctuating binding behavior with NGF which can be accounted for by its long linear structure. ADME-Tox studies further confirmed the potency of these phytochemicals as BPA violated no factors and Vitamin E, Stigmasterol and Nonacosane violated 1 factor for Lipinski's rule. Moreover, their high human intestinal absorption and bioavailability score along with their classification as non-mutagen in the Ames test makes these compounds more reliable as potent antineurodegenerative drugs. Our study provides an in-silico approach toward understanding the anti-neurodegenerative property of Bacopa monnieri phytochemicals and establishes the role of four major phytochemicals which can be utilized as a replacement for synthetic drugs against several neurodegenerative disorders.

Bio-Oriented Synthesis and Molecular Docking Studies of 1,2,4-Triazole Based Derivatives as Potential Anti-Cancer Agents against HepG2 Cell Line.

Triazole-based acetamides serve as important scaffolds for various pharmacologically active drugs. In the present work, structural hybrids of 1,2,4-triazole and acetamides were furnished by chemically modifying 2-(4-isobutylphenyl) propanoic acid (1). Target compounds 7a-f were produced in considerable yields (70-76%) by coupling the triazole of compound 1 with different electrophiles under different reaction conditions. These triazole-coupled acetamide derivatives were verified by physiochemical and spectroscopic (HRMS, FTIR, 13CNMR, and 1HNMR,) methods. The anti-liver carcinoma effects of all of the derivatives against a HepG2 cell line were investigated. Compound 7f, with two methyl moieties at the ortho-position, exhibited the highest anti-proliferative activity among all of the compounds with an IC50 value of 16.782 µg/mL. 7f, the most effective anti-cancer molecule, also had a very low toxicity of 1.190.02%. Molecular docking demonstrates that all of the compounds, especially 7f, have exhibited excellent binding affinities of -176.749 kcal/mol and -170.066 kcal/mol to c-kit tyrosine kinase and protein kinase B, respectively. Compound 7f is recognized as the most suitable drug pharmacophore for the treatment of hepatocellular carcinoma.

Design, synthesis, bioactivity and mechanism of action of novel myricetin derivatives containing amide and hydrazide

A series of myricetin derivatives containing amide and hydrazide were designed and synthesized. All the compounds were characterized by NMR and HRMS. Bioactivity test showed that some of the target compounds had excellent anti-tobacco mosaic virus (TMV) activity. In particular, the median effective concentration (EC50) values of the anti-TMV curative and protective activities of N-(2-(2-(2-((5,7-dimethoxy-4-oxo-2-(3,4,5-trimethoxyphenyl)-4H-chromen-3-yl)oxy)acetyl)hydrazineyl)-2-oxoethyl)-4-(trifluoromethyl)benzamide (G9) were 202.3 and 164.0 μg/mL respectively, superior to ningnanmycin (329.1, 230.3 μg/mL). Microscale thermophoresis (MST) and molecular docking showed that G9 had an excellent binding affinity with tobacco mosaic virus coat protein (TMV-CP) (Kd = 0.158 ± 0.024 μM), which was better than that of ningnanmycin (Kd = 2.074 ± 0.818 μM). Moreover, there were many interaction forces between G9 and the key amino acid residues of TMV-CP. The chlorophyll content and peroxidase (POD) activity of tobacco leaves treated with G9 increased significantly, indicating that G9 could improve the photosynthesis of tobacco leaves and stimulate the resistance of tobacco leaves to TMV. The insecticidal activity of G9 against Mythimna separata (M. separate) was found to be 95.2% at 200 μg/mL, which was close to bufenozide (100%). The insecticidal activity of myricetin was significantly improved after the introduction of active groups of amide and hydrazide, which could be further explored.

Cellular mechanism of action of forsythiaside for the treatment of diabetic kidney disease.

Background: Diabetic kidney disease (DKD) becomes the leading cause of death for end-stage renal disease, whereas the potential mechanism is unclear and effective therapy is still rare. Our study was designed to investigate the cellular mechanism of Forsythiaside against DKD. Materials and Methods: The targets of Forsythiaside and the DKD-related targets were obtained from databases. The overlapping targets in these two sets were regarded as potential targets for alleviation of DKD by Forsythiaside. The targets of diabetic podocytopathy and tubulopathy were also detected to clarify the mechanism of Forsythiaside ameliorating DKD from the cellular level. Results: Our results explored that PRKCA and RHOA were regarded as key therapeutic targets of Forsythiaside with excellent binding affinity for treating DKD podocytopathy. Enrichment analysis suggested the underlying mechanism was mainly focused on the oxidative stress and mTOR signaling pathway. The alleviated effects of Forsythiaside on the reactive oxidative species accumulation and PRKCA and RHOA proteins upregulation in podocytes were also confirmed. Conclusion: The present study elucidates that Forsythiaside exerts potential treatment against DKD which may act directly RHOA and PRKCA target by suppressing the oxidative stress pathway in podocytes. And Forsythiaside could be regarded as one of the candidate drugs dealing with DKD in future experimental or clinical researches.

Exploring the binding effects and inhibiting mechanism of hyperoside to lipase using multi-spectroscopic approaches, isothermal titration calorimetry, inhibition kinetics and molecular dynamics.

Hyperoside (HYP) is a flavonoid with various physiological activities. The present study examined the interaction mechanism between HYP and lipase using multi-spectrum and computer-aided techniques. Results demonstrated that the force type of HYP on lipase was mainly hydrogen bond, hydrophobic interaction force, and van der Waals force, and HYP had an excellent binding affinity with lipase at 1.576 × 105 M-1. HYP dose-dependently inhibited lipase in the inhibition experiment, and its IC50 value was 1.92 × 10-3 M. Moreover, the results suggested that HYP could inhibit the activity by binding to essential groups. Conformational studies indicated that the conformation and microenvironment of lipase were slightly changed after the addition of HYP. Computational simulations further confirmed the structural relationships of HYP to lipase. The interaction between HYP and lipase can provide ideas for the development of functional foods related to weight loss. The results of this study help comprehend the pathological significance of HYP in biological systems, as well as its mechanism.

Virtual screening of novel pyridine derivatives as effective inhibitors of DNA gyrase (GyrA) of salmonella typhi

In a bid to discovering novel antibiotics to combat growing trend of multi-drug resistance strains of Salmonella typhi, 48 new pyridine derivatives with significant inhibitory activities against the aforementioned bacterium were subjected to molecular docking against DNA gyrase protease of the bacterium, drug likeness evaluation and pharmacokinetics profiling. All the 48 leads displayed better binding affinity values when compared with Amoxicillin, Ciprofloxacin, Ceftriaxone, Ampicillin, and chloramphenicol, the standard antibiotics used herein for quality assurance. Furthermore, the majority of the compounds were, however, screened out due to their poor pharmacokinetics profiles and drug-likeness. Only five compounds emerged as the most promising leads and they include C4 with binding affinity of -8.0 kcal/mol, C8 (-8.6 kcal/mol), C9 (-8.1 kcal/mol), C26 (-8.3 kcal/mol), and C27 (-8.0 kcal/mol). These compounds not only displayed better binding affinity when compared with the reference antibiotics but also exhibit different modes of interactions with the target protease of the bacterium making them more potent and drug like. Toxicity evaluation of the leads also revealed that the compounds are neither tumorigenic nor mutagenic. In view of the excellent binding affinity, high pharmacokinetics profile and positive drug-likeness of the novel ligands, we recommend these promising compounds for in vitro and in vivo studies in order to discover novel antibiotics that could curb the dangerous trend of multiple drug resistance by Salmonella typhi.

Design and Synthesis of Conformationally Flexible Scaffold as Bitopic Ligands for Potent D3-Selective Antagonists.

Previous studies have confirmed that the binding of D3 receptor antagonists is competitively inhibited by endogenous dopamine despite excellent binding affinity for D3 receptors. This result urges the development of an alternative scaffold that is capable of competing with dopamine for binding to the D3 receptor. Herein, an SAR study was conducted on metoclopramide that incorporated a flexible scaffold for interaction with the secondary binding site of the D3 receptor. The alteration of benzamide substituents and secondary binding fragments with aryl carboxamides resulted in excellent D3 receptor affinities (Ki = 0.8-13.2 nM) with subtype selectivity to the D2 receptor ranging from 22- to 180-fold. The β-arrestin recruitment assay revealed that 21c with 4-(pyridine-4-yl)benzamide can compete well against dopamine with the highest potency (IC50 = 1.3 nM). Computational studies demonstrated that the high potency of 21c and its analogs was the result of interactions with the secondary binding site of the D3 receptor. These compounds also displayed minimal effects for other GPCRs except moderate affinity for 5-HT3 receptors and TSPO. The results of this study revealed that a new class of selective D3 receptor antagonists should be useful in behavioral pharmacology studies and as lead compounds for PET radiotracer development.

Anti-proliferative activity, molecular docking study of novel synthesized ethoxyphenylbenzene sulfonamide with computational calculations

In this elucidation, we synthesized novel benzenesulfonamide and examined its biological evaluation. Firstly, the reaction of 2-allylphenol(1) with 1,2-dibromoethane(2) to afford the corresponding 1-allyl-2-(2-bromoethoxy)benzene(3) which easily isomerized with PdCl2 to afford the (E)-1-(2-bromoethoxy)-2-(prop-1-en-1-yl)benzene (4). Moreover, using the Williamson reaction of compound 4 with o-acetamidophenol gives different acetamide derivatives 6. Furthermore, the acid hydrolysis of compound 6 to afford the corresponding 2-[2-(2-Propenyl-phenoxy)-ethoxy]-phenylamine (8) which reacts with p-toluene sulphonyl chloride to afford the corresponding (E)-4-methyl-N-(2-(2-(2-(prop-1-en-1-yl)phenoxy)ethoxy)phenyl) benzene sulfonamide (10). The reactivity of compound 10 with bromo derivatives utilized microwave irradiation at 100°C to afford the corresponding benzenesulfonamide derivatives 11a-c. The benzenesulfonamide derivatives 11a-c exhibited in-vitro antitumor activity against HepG2 and MCF-7 tumor cells. Additionally, molecular docking simulation on these benzenesulfonamides with (PDB ID: 4hdq) and (PDB ID: 5H38) proteins to know their hydrogen bond interaction with different amino acids and showed the excellent binding affinity energy of compound 11a with -12.621, -10.621kcal/mol and the shortage bond length with 1.32-2.62 Å and attached mostly with different amino acids and this stability revealed to delocalization of benzene rind which attached with two moieties. Furthermore, the computational calculation studies of synthesized compounds were optimized using the DFT/ B3LYP/6-311G(d) basis set to confirm stabilities through physical descriptors, MEP, ESP, and band energy gap.

Structural Analysis and In-Silico Inhibitor Interaction Studies of Leishmania donovani Heat-Shocked Proteins 83 (HSP83)

Leishmaniasis is a parasite disease prevalent in 88 nations worldwide, causing high morbidity and mortality in most developing countries. Since no vaccine or pharmaceutical treatment with the best therapeutic window is available, the World Health Organization has listed Leishmaniasis as a priority disease. The enzyme heat shock protein 83 (Hsp83), which is frequently found in cells, catalyzes cellular biological pathways to carry out tasks such as protein folding, intracellular protein trafficking, acquired thermotolerance, differentiation, adaptability, pathogenicity, persistence in the host cell and preventing proteins from being damaged by heat and other stresses. Therefore, HSP actively rewires cellular functions and signalling pathways, which is crucial for cell survival. Inhibition of HSP may interfere with pathogenesis and virulence by impairing several processes. Therefore, L. donovani heat shock protein 83 (LdHsp83) has been suggested as a potential leishmaniasis therapeutic target. Thus, in this study, we built the structure of HSP83 by homology modelling. We used Leishmania primary HSP90 crystal structure (PDB ID 3HJCA) as a template for constructing 3D models of LdHSP83 by comparative modelling approach using SWISS-MODEL, Phyre, GENO 3D program server and Prime 2.1 (Maestro 9.1, Schrodinger 2010) program tool. Based on overall stereochemical quality (PROCHECK, DOPE, Verify 3D), the best model was selected and further used for structural analysis. The energy-minimized, refined and characterized model was further investigated for antileishmanial activity with currently available antileishmanial drugs and enumerated virtual library of chemical compounds through a docking approach. A few combinations, including oxmetidine, had an excellent binding affinity with the Hsp83, as indicated by Glide Score (G Score) and Gold Fitness Score. These potential inhibitors were further studied for SAR and ADMET properties, respectively, by TSAR 3.3 and Qikprop 2.3, indicating the safety and efficacy of these compounds. Once preclinically and clinically examined, these compounds may further be implemented in leishmaniasis therapy.

Three on Three: Universal and High-Affinity Molecular Recognition of the Symmetric Homotrimeric Spike Protein of SARS-CoV-2 with a Symmetric Homotrimeric Aptamer.

Our previously discovered monomeric aptamer for SARS-CoV-2 (MSA52) possesses a universal affinity for COVID-19 spike protein variants but is ultimately limited by its ability to bind only one subunit of the spike protein. The symmetrical shape of the homotrimeric SARS-CoV-2 spike protein presents the opportunity to create a matching homotrimeric molecular recognition element that is perfectly complementary to its structural scaffold, causing enhanced binding affinity. Here, we describe a branched homotrimeric aptamer with three-fold rotational symmetry, named TMSA52, that not only possesses excellent binding affinity but is also capable of binding several SARS-CoV-2 spike protein variants with picomolar affinity, as well as pseudotyped lentiviruses expressing SARS-CoV-2 spike protein variants with femtomolar affinity. Using Pd-Ir nanocubes as nanozymes in an enzyme-linked aptamer binding assay (ELABA), TMSA52 was capable of sensitively detecting diverse pseudotyped lentiviruses in pooled human saliva with a limit of detection as low as 6.3 × 103 copies/mL. The ELABA was also used to test 50 SARS-CoV-2-positive and 60 SARS-CoV-2-negative patient saliva samples, providing sensitivity and specificity values of 84.0 and 98.3%, respectively, thus highlighting the potential of TMSA52 for the development of future rapid tests.

D1018 with higher stability and excellent lipopolysaccharide binding affinity has potent anti-bacterial and anti-inflammatory activity.

Escherichia coli (E. coli) infection and LPS-induced inflammation are still of severe threat to human health. With the increasing problem of antibiotic resistance, there is a desperate need to develop new approaches to solve the problem. Antimicrobial peptide (AMP) IDR-1018 exhibited potential antimicrobial and immunoregulation activity. However, moderate antimicrobial efficiency and susceptibility to protease cleavage limited its therapeutic application. Therefore, the derived 1018M which has better activity against MRSA and whole sequence D-amino acids substitution peptides (D1018 and D1018M) were synthesized in this study. The resistance of D1018 and D1018M against tested proteases increased (2-4 times), particularly in D1018. The antibacterial activity of D1018 was the same as that of the parent peptide IDR-1018, but the antimicrobial activity of D1018M was slightly increased (2-fold). Though the hemolysis of IDR-1018 and D1018 was about 2%, at the concentration of 8×MIC, the cytotoxicity of IDR-1018, D1018, and 1018M was negligible. The peptides could interact with E. coli cell wall and cytoplasmic membrane, penetrate the membrane, cause leakage of contents, and disrupt genomic DNA. Among them, D1018 is the most prominent one. In addition, IDR-1018 and D1018 showed potent binding ability to LPS, thus leading to excellent inhibition capacity to LPS-induced proinflammation response. Taken together, these data demonstrate that D1018 is a promising peptide candidate for the treatment of E. coli infection.

Exploration of Chemopreventive Potential of Linalool in Targeting Lung Cancer Biomarkers.

Phytochemicals are used to treat lung cancer in contemporary and traditional medicine. The limitations of known chemotherapeutic drugs such as non-specificity, resistance, and toxicity restrict their use for lung cancer treatment. Therefore, the search for target-specific novel entities is required continuously. Linalool, a monoterpene alcohol that possesses antiviral, anti-inflammatory, and antibacterial properties, is present in sweet basil, laurel, jasmine, rosewood, and lavender. Previous reports revealed its anticancer potential against colon, breast, and liver cancer. In this study, linalool's efficacy in targeting biomarkers associated with different lung cancer stages has been investigated. The in silico molecular docking analysis was used to explore drug-receptor interaction, and further, linalools cytotoxicity potential was evaluated on lung adenocarcinoma cell line (A549). The toxicity profiling of linalool was done by ADMET analysis. In the results, Linalool revealed an excellent binding affinity with the selected targets. It showed the highest interaction with BRAF with the binding energy of -5.6 kcal/mol. Furthermore, it successfully interacts within the binding pocket of BRAF, similar to its inhibitor (Sorafenib). In MTT analysis, linalool significantly reduces the percent viability IC30 474.94 ± 43.12, 379.33 ± 49.5, and 183.77 ± 66.7 μM in A549 cell lines for 24, 48, and 72 h, respectively. These results concluded that linalool possesses chemopreventive potential against lung cancer by interacting or modulating selected biomarkers associated with a lung cancer diagnosis, progression, and proliferation.

Peptide-anchored biomimetic interface for electrochemical detection of cardiomyocyte-derived extracellular vesicles.

Cardiomyocyte-derived extracellular vesicles (EVs) are a promising class of biomarkers that can advance the diagnosis of many kinds of cardiovascular diseases. Herein, we develop a new electrochemical method for the feasible detection of cardiomyocyte-derived EVs in biological fluids. The core design of the method is the fabrication of a peptide-anchored biomimetic interface consisting of a lipid bilayer and peptide probes. On the one hand, the lipid bilayer provides excellent antifouling ability to the electrode interface and facilitates the anchoring of peptide probes. On the other hand, the peptide probes equip the electrode interface with excellent binding capability and affinity to CD172a, a specific marker of cardiomyocyte-derived EVs, thus enabling the efficient and selective detection of target EVs. Taking EVs derived from the heart myoblast cells H9C2 as the model target, the method displays a wide linear detection range from 1 × 103 to 1 × 108 particles/mL with a desirable detection limit of 132 particles/mL. Furthermore, the method shows good performance in biological fluids such as serum, and thus may have great potential for practical use in the diagnosis of cardiovascular diseases.

In-situ polymerization of polycarbazole-zinc oxide nanocomposite: An in silico docking model and in vitro antibacterial biomaterial

The current study focuses on the synthesis of polycarbazole-zinc oxide (PCz/ZnO) nanocomposite and its application as an in vitro antibacterial biomaterial as well as an in silico docking model. The synthesized pristine polymer, polycarbazole (PCz) and its nanocomposite PCz/ZnO were characterized by Fourier transform infrared (FT-IR), Thermo-gravimetry/Differential Thermo-gravimetry (TG-DTG), X-ray diffraction (XRD), Field Emission Scanning Electron Microscopy (FE-SEM), Brunauer-Emmett-Teller (BET), Energy-dispersive X-ray (EDX), Raman and X-ray photoelectron spectroscopic (XPS) techniques. FT-IR, XRD, FE-SEM, and XPS studies revealed that the polymerization of Cz has been successfully achieved on the surfaces of ZnO nanoparticles, indicating the strong interfacial interaction between PCz and ZnO nanoparticles. However, TG-DTG studies revealed that the nanocomposite, PCz/ZnO, proved thermally more stable compared to the pristine polymer, PCz. Further, the pristine PCz and PCz/ZnO nanocomposite were evaluated for antibacterial activity against Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Staphylococcus aureus. The nanocomposite PCz/ZnO showed the highest zone of inhibition against K. Pneumoniae (17 mm), followed by P. aeruginosa (16 mm), then S. aureus (14 mm) and E. coli (19 mm) at 80 mg ml−1. Significantly, the in silico molecular docking predicts the modes of interactions of PCz and PCz/ZnO with B-DNA. Briefly, the results obtained from in silico molecular docking studies of the pristine PCz and PCz/ZnO nanocomposite with negative free binding energies (-7.1 kcal mol−1 of PCz and −6.23 kcal mol−1 of PCz/ZnO) imply an excellent and favourable binding affinity vis-à-vis interaction modes of both pristine PCz and PCz/ZnO nanocomposite (drugs) with B-DNA bases (target).

Potential Epha2 Receptor Blockers Involved in Cerebral Malaria from Taraxacum officinale, Tinospora cordifolia, Rosmarinus officinalis and Ocimum basilicum: A Computational Approach.

Cerebral malaria (CM) is a severe manifestation of parasite infection caused by Plasmodium species. In 2018, there were approximately 228 million malaria cases worldwide, resulting in about 405,000 deaths. Survivors of CM may live with lifelong post-CM consequences apart from an increased risk of childhood neurodisability. EphA2 receptors have been linked to several neurological disorders and have a vital role in the CM-associated breakdown of the blood-brain barrier. Molecular docking (MD) studies of phytochemicals from Taraxacum officinale, Tinospora cordifolia, Rosmarinus officinalis, Ocimum basilicum, and the native ligand ephrin-A were conducted to identify the potential blockers of the EphA2 receptor. The software program Autodock Vina 1.1.2 in PyRx-Virtual Screening Tool and BIOVIA Discovery Studio visualizer was used for this MD study. The present work showed that blocking the EphA2 receptor by these phytochemicals prevents endothelial cell apoptosis by averting ephrin-A ligand-expressing CD8+ T cell bioadhesion. These phytochemicals showed excellent docking scores and binding affinity, demonstrating hydrogen bond, electrostatic, Pi-sigma, and pi alkyl hydrophobic binding interactions when compared with native ligands at the EphA2 receptor. The comparative MD study using two PDB IDs showed that isocolumbin, carnosol, luteolin, and taraxasterol have better binding affinities (viz. -9.3, -9.0, -9.5, and -9.2 kcal/mol, respectively). Ocimum basilicum phytochemicals showed a lower docking score but more binding interactions than native ligands at the EphA2 receptor for both PDB IDs. This suggests that these phytochemicals may serve as potential drug candidates in the management of CM. We consider that the present MD study provides leads in drug development by targeting the EphA2 receptor in managing CM. The approach is innovative because a role for EphA2 receptors in CM has never been highlighted.

Imidazole-pyridine hybrids as potent anti-cancer agents

In the current investigation, fifteen novel imidazole-pyridine-based molecules were synthesized and tested against cell lines of the lung (H1299) and colon (HCT116) adenocarcinomas by proliferation assay. The results demonstrated that compounds 5a, 5d, 5e, and 5f were the most active (IC50<30 µM). Based on recent literature and the current results, the glycogen synthase kinase-3β (GSK-3β) protein was investigated in-silico as a possible target. The molecular docking and QSAR revealed an excellent binding affinity of the selected imidazole-pyridine compounds to GSK-3β. Notably, GSK-3β protein levels were significantly upregulated in hepatocellular liver carcinoma (LIHCs) tissues and negatively affected patient prognosis. Consequently, the compounds were evaluated on liver cancer cell lines (HepG2, HUH-7, and PLC/PRF/5) by the MTT assay, and 5d showed the highest antitumor activity. This study offers new compounds with interesting biological activity on GSK-3β as a target, exhibiting a potential therapeutic impact for hepatocellular carcinoma patients.

Deep fluoride removal from the sulfate leaching solution of spent LIBs by complexation extraction with Al3+ loaded solvent

Fluoride contained in the leaching solution of spent lithium-ion batteries (LIBs) not only decreased product quality, but also led to severe equipment corrosion and potential environmental hazards. Therefore, a coordination extraction system using di-(2-ethylhexyl) phosphoric acid (D2EHPA) loaded with aluminum ions (Al3+) as extractant was designed to deeply remove fluoride from the sulfate leaching solution of spent LIBs that combined the excellent binding affinity of Al3+ to fluoride and the perfect chemical efficiency of solvent extraction. The effects of D2EHPA concentration, loaded Al3+ concentration, equilibrium pH and shaking time on the extraction efficiency of fluoride were investigated. Experimental results indicated that over 99 % of fluoride was selectively extracted and the fluoride concentration in the leaching solution of spent LIBs was reduced from 210 mg/L to 2 mg/L by single-stage extraction, meeting the requirement of fluoride content in the battery grade Ni/Co/Mn sulfate solution and the wastewater discharge standards. The loaded organic phase was scrubbed and stripped by diluted H2SO4, and fluoride could be fully stripped into the stripping solution. Further characterization studies revealed that Al3+ and D2EHPA may mainly coordinate in the form of AlL3·HL in the Al-loaded organic phase (HL denotes D2EHPA). After the Al-loaded organic phase was contacted with solution containing fluoride, a structure of AlFL2·HL coordinated with F- was formed. This study provides a novel technical approach to improve product quality and reduce fluoride wastewater pollution for the recycling process of spent LIBs.

Synthesis, evaluation and mechanism exploration of 2-(N-(3-nitrophenyl)-N-phenylsulfonyl)aminoacetohydroxamic acids as novel urease inhibitors

Thirteen 2-(N-(3-nitrophenyl)-N-phenylsulfonyl)aminoacetohydroxamic acids which were reported for the first time were designed and synthesized as novel urease inhibitors. Most of them showed higher potency than the positive control acetohydroxamic acid, with 2-(N-(3-nitrophenyl)-N-(4-bromophenylsulfonyl)aminoacetohydroxamic acid (d7) being the most active (IC50 = 0.13 ± 0.01 μM). Compound d7 reversibly inhibits urease with mixed mechanism showing excellent binding affinity to urease active site (KD = 0.34 nM, Ki=0.065 ± 0.003 µM andKi′ = 1.20 ± 0.09 µM) and very low cytotoxicity against mammalian cells (cell viability of 91.4 % against HepG2 at 250 μg/mL). These positive results indicated that d7 may be used as the lead for further research to develop urease inhibitors with promising properties.

Experimental, DFT, molecular docking and in silico ADMET studies of cadmium-benzenetricarboxylates

The structure of the polymer [Cd(BTC)(H2O)2]n was identified by X-ray single-crystal crystallography. The complex’s stability and overall reactivity were examined at the B3LYP/6-311++G (d,p) level of theory whereas the lighter elements (H, C, and O) were studied using the LanL2DZ basis set. The electron distribution in the complex’s highest occupied molecular orbital is solely concentrated in a small area, with no electrons distributed over the cadmium. Consequently, the electrons in the complex’s lowest unoccupied molecular orbital (LUMO) were dispersed equally. The Cd atom is partially obscured by charge delocalization in the LUMO. The natural bond orbital analysis supports the result for reactivity studies. The rate of absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the complex evaluated by molecular docking in a bid allowed comprehend the biological applicability. The [Cd(BTC)(H2O)2]n exhibited excellent binding affinity with proteins 1D7U and 2XCS, while by ADMET it is suggested that cytotoxicity and carcinogenicity were inactive. It is clearly shown that the complex has strong biological uses, notably for the treatment of microbial diseases.

Experimental, DFT, molecular docking and in silico ADMET studies of cadmium-benzenetricarboxylates

The structure of the polymer [Cd(BTC)(H2O)2]n was identified by X-ray single-crystal crystallography. The complex’s stability and overall reactivity were examined at the B3LYP/6-311++G (d,p) level of theory whereas the lighter elements (H, C, and O) were studied using the LanL2DZ basis set. The electron distribution in the complex’s highest occupied molecular orbital is solely concentrated in a small area, with no electrons distributed over the cadmium. Consequently, the electrons in the complex’s lowest unoccupied molecular orbital (LUMO) were dispersed equally. The Cd atom is partially obscured by charge delocalization in the LUMO. The natural bond orbital analysis supports the result for reactivity studies. The rate of absorption, distribution, metabolism, excretion, and toxicity (ADMET) of the complex evaluated by molecular docking in a bid allowed comprehend the biological applicability. The [Cd(BTC)(H2O)2]n exhibited excellent binding affinity with proteins 1D7U and 2XCS, while by ADMET it is suggested that cytotoxicity and carcinogenicity were inactive. It is clearly shown that the complex has strong biological uses, notably for the treatment of microbial diseases.