Lower Interaction Energy Research Articles

Quantitative investigations of intermolecular interactions in 2-amino-3-nitropyridine polymorphs: Inputs from quantum mechanical calculations

Two polymorphic forms (Form–I and Form–II) of 2-amino-3-nitropyridine are structurally characterized by single crystal X-ray diffraction analysis and compared with another polymorphic form (Form–III, retrieved from CSD) with a detailed analysis of the Hirshfeld surfaces and fingerprint plots facilitating a comparison of intermolecular interactions. X-ray crystallography exposes that the polymorphs generate completely different network structures through hydrogen bonding interactions. Polymorphic Form–I exhibit a layer assembly through the cooperative face-to-face π⋯π and lone pair⋯π interactions, whereas Form–II, and Form–III displays hydrogen bonds only. A detailed investigation of Hirshfeld surface analysis reveals much more detailed scrutiny of intermolecular interactions experienced by the polymorphic forms of 2-amino-3-nitropyridine. The quantitative analysis of the interaction energies involving various noncovalent interactions was computed and compared to get a deeper insight into the role of such interactions in stabilizing the polymorphs. The interaction energies of non-covalent interactions are calculated through theoretical DFT calculations as well as the PIXEL method. The PIXEL method provides us precise interaction energy calculation with an energy decomposition scheme. Higher electrostatic interaction shows higher interaction energy while the lower interaction energy corresponds to the higher dispersive interaction. The lattice energies of the polymorphs are also obtained via the PIXEL method. The nature and strength of these interactions have been studied using Bader's quantum theory of atoms in molecules. The topological analysis unequivocally establishes the presence of (3, −1) bond critical point, suggesting that the intermolecular interactions are closed-shell interactions. The NCI (Non-covalent Interaction) plots are further employed to identify and characterize the non-covalent interactions of the polymorphs.

New insight into the structure nature for Pb-starch colloidal depressant from experiments and DFT calculations

Starch is a traditional depressant for fine minerals, whilst this depressant difficultly inhibits fine calcite and chlorite. This study presents that the chelation of starch with lead ions could significantly increase the inhibiting ability, which effectively decrease the recovery of fine calcite and chlorite to 28.81 % and 20.11 %. When the starch coordinates with lead ions, the particle size and the surface charge are increased obviously. Meanwhile, the Fourier transform infrared spectroscopy illustrate the shift of initial functional group, and the O-Pb functional group appears at wavelength of 3513.72 cm−1. The X-ray photoelectron spectroscopy determine the Pb atoms concentration increases to 9.59 %, and the Pb-group characteristic peaks generate at binding energy of 138.23 eV and 143.11 eV. Furthermore, the cluster calculation presents the trans-glucose of single starch molecule is easier chelated with lead ions than the cis-glucose. And the optimal configuration of Pb-starch is the lead ions chelate the O6 and O1 atoms of trans-glucose structure to form the O1-Pb-O6 structure with a shortest average band length and a lowest interaction energy. Besides, during the chelation, the Pb contributes empty orbitals to accept the donated electrons of glucose. Therefore, this study deeply determines the structure nature of Pb-starch colloidal depressant.

Crystal facet-dependent reduction behavior of α-Fe2O3 in hydrogen atmosphere

The reduction of α-Fe2O3 is significant in heterogeneous catalysis. However, due to the changeable crystal phase and the transformation of crystal facet, its reduction mechanism still needs further clarification. In this work, α-Fe2O3 rhombohedra, hexagonal-plate and pseudo-cubic with the facets of (104), (001) and (102) respectively were synthesized, and the evolutions of α-Fe2O3 structures during H2 reduction were investigated by multiple means including in-situ XRD. It found that the reduction of α-Fe2O3 showed a facet-dependent behavior in H2 atmosphere, that is different facets exhibited completely different rates and phase transition pathways. Specifically, the Fe2O3 (104) and Fe3O4 (220) had the fastest reduction rate in α-Fe2O3 → Fe3O4 and Fe3O4 → α-Fe, respectively, which was attributed to the higher concentration of oxygen vacancies on the corresponding crystal facets. The phase transition paths for Fe2O3 (102) and Fe2O3 (104) were α-Fe2O3 → Fe3O4 → α-Fe, while Fe2O3 (001) was α-Fe2O3 → Fe3O4 → FeO → α-Fe. Additionally, DFT calculations further revealed that Fe2O3 (104) and Fe3O4 (220) had lower interaction energy between O and Fe atoms and easily formed oxygen vacancy. Consequently, these facets presented different formation rates of H2O, leading to significant differences in the phase transition process.

In silico characterization of ligand-receptor interactions for U-47700, N,N-didesmethyl-U-47700, U-50488 at mu- and kappa-opioid receptors.

The increasing misuse of novel synthetic opioids (NSOs) represents a serious public health concern. In this regard, U-47700 (trans-3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide) and related "U-compounds" emerged on recreational drug markets as synthetic substitutes for illicit heroin and constituents of counterfeit pain medications. While the pharmacology of U-compounds has been investigated using in vitro and in vivo methods, there is still a lack of understanding about the details of ligand-receptor interactions at the molecular level. To this end, we have developed a molecular modeling protocol based on docking and molecular dynamics simulations to assess the nature of ligand-receptor interactions for U-47700, N,N-didesmethyl U-47700, and U-50488 at the mu-opioid receptor (MOR) and kappa-opioid receptor (KOR). The evaluation of ligand-receptor and ligand-receptor-membrane interaction energies enabled the identification of subtle conformational shifts in the receptors induced by ligand binding. Interestingly, the removal of two key methyl groups from U-47700, to form N,N-didesmethyl U-47700, caused a loss of hydrogen bond contact with tryptophan (Trp)229, which may underlie the lower interaction energy and reduced MOR affinity for the compound. Taken together, our results are consistent with the reported biological findings for U-compounds and provide a molecular basis for the MOR selectivity of U-47700 and KOR selectivity of U-50488.

Quinolinones Alkaloids with AChE Inhibitory Activity from Mangrove Endophytic Fungus Penicillium citrinum YX-002.

Acetylcholinesterase (AChE) inhibitory activity-guided studies on the mangrove-derived endophytic fungus Penicillium citrinum YX-002 led to the isolation of nine secondary metabolites, including one new quinolinone derivative, quinolactone A (1), a pair of epimers quinolactacin C1 (2) and 3-epi-quinolactacin C1 (3), together with six known analogs (4-9). Their structures were elucidated based on extensive mass spectrometry (MS) and 1D/2D nuclear magnetic resonance (NMR) spectroscopic analyses, and compared with data in the literature. The absolute configurations of compounds 1-3 was determined by combination of electronic circular dichroism (ECD) calculations and X-Ray single crystal diffraction technique using CuKα radiation. In bioassays, compounds 1, 4 and 7 showed moderate AChE inhibitory activities with IC50 values of 27.6, 19.4 and 11.2 μmol/L, respectively. The structure-activity relationships (SARs) analysis suggested that the existence of carbonyl group on C-3 and the oxygen atom on the five-membered ring were beneficial to the activity. Molecular docking results showed that compound 7 had a lower affinity interaction energy (-9.3 kcal/mol) with stronger interactions with different sites in AChE activities, which explained its higher activities.

Diethylenetriamine and serine as synergists used in FA/OII based alkaline solution to realize enhanced cleaning efficiency of the organic corrosion inhibitor

In industrial chemical mechanical polishing (CMP), 5-methyl benzotriazole (MBTA) as a substitute organic inhibitor of benzotriazole has shown great effect in low usage compared to other benzo derivatives. However, it also brings considerable challenges to subsequent post-CMP cleaning due to its hydrophobic property. In this work, diethylenetriamine (DETA) and serine were used as synergists in FA/OII-based alkaline solutions to achieve enhanced removal of MBTA. Contact angle and electrochemical tests proved the weak cleaning performance of FA/OII was generally improved after adding DETA or serine. Especially, 400 ppm serine displayed its superiority with the lowest contact angle and the highest corrosion current density of 24.2° and 1.023 μA/cm2. Then, static observation and X-ray photoelectron spectra analysis confirmed they could break Cu(I)-MBTA and form precipitates like DETA/serine-MBTA. Copper loss after cleaning was also measured by an atomic force microscope and the corresponding surface morphology still needed to be improved by adding proper surfactants. Finally, with the assistance of density functional theory calculation and molecular dynamic simulation, the active sites and reactivity of both reagents were concluded by comparing their intrinsic properties and interaction configurations. Serine turned out to work better than DETA with a lower interaction energy of − 724.83 Kcal/mol.

Nitric acid oxidation and urea modification of carbon fibres as biofilm carriers

ABSTRACT Carbon fibres (CF) are commonly used as carriers in biofilm-based wastewater treatment. The surface properties of the CF are herein modified using a combination of nitric acid oxidation and urea to optimise the carrier to immobilise bacterial cells. The capacity of the CF carriers to immobilise bacterial cells and activated sludge is evaluated using bacterial cell adhesion and sludge immobilisation tests. The total interaction energy profiles between the CF supports and bacterial cells were calculated according to the Derjaguin–Landau–Verwey–Overbeek (DLVO) theory to explain the mechanism by which these modifications enhance this immobilisation capacity. CF-U has a high capacity for immobilising bacterial cells and activated sludge (3.7 g-sludge/g-CF supports) owing to its low total interaction energy. Nitric acid oxidation reduced the diiodomethane contact angle of CF from 55.1° to 38.5°, which reduced the Lifshitz-van der Waals interaction energy, while urea modification further increased the zeta potential of CF from 12.8 mV to −0.7 mV, thereby reducing the electrostatic interaction energy. Experiments and DLVO theory both determined that a combination of nitric acid oxidation and urea modification significantly enhanced the ability of CF to immobilise microorganisms.

Fine tuning rigid body docking results using the Dreiding force field: A computational study of 36 known nanobody-protein complexes.

This paper aims to understand the binding strategies of a nanobody-protein pair by studying known complexes. Rigid body protein-ligand docking programs produce several complexes, called decoys, which are good candidates with high scores of shape complementarity, electrostatic interactions, desolvation, buried surface area, and Lennard-Jones potentials. However, the decoy that corresponds to the native structure is not known. We studied 36 nanobody-protein complexes from the single domain antibody database, sd-Ab DB, http://www.sdab-db.ca/. For each structure, a large number of decoys are generated using the Fast Fourier Transform algorithm of the software ZDOCK. The decoys were ranked according to their target protein-nanobody interaction energies, calculated by using the Dreiding Force Field, with rank 1 having the lowest interaction energy. Out of 36 protein data bank (PDB) structures, 25 true structures were predicted as rank 1. Eleven of the remaining structures required Ångstrom size rigid body translations of the nanobody relative to the protein to match the given PDB structure. After the translation, the Dreiding interaction (DI) energies of all complexes decreased and became rank 1. In one case, rigid body rotations as well as translations of the nanobody were required for matching the crystal structure. We used a Monte Carlo algorithm that randomly translates and rotates the nanobody of a decoy and calculates the DI energy. Results show that rigid body translations and the DI energy are sufficient for determining the correct binding location and pose of ZDOCK created decoys. A survey of the sd-Ab DB showed that each nanobody makes at least one salt bridge with its partner protein, indicating that salt bridge formation is an essential strategy in nanobody-protein recognition. Based on the analysis of the 36 crystal structures and evidence from existing literature, we propose a set of principles that could be used in the design of nanobodies.

Revealing mechanism of non-Arrhenius viscosity change in metal melts based on Wulff cluster model

In some metal melts, like Pb and Al, viscosity as a function of temperature does not obey Arrhenius law in some temperature range, so called non-Arrhenius viscosity change. In this paper, the Wulff cluster model combined with phonon calculations is used to investigate the relation between the structural characteristic and the non-Arrhenius viscosity change in metallic melts. Although the surface energy of the Wulff clusters in melts does not change significantly with temperature, the Wulff shape changed evidently. For both Pb and Al, one surface of the Wulff shape disappears (Pb(321) and Al(100)) when the non-Arrhenius viscosity change occurs upon heating. The trend of the non-Arrhenius viscosity change is strongly related to the properties of the disappeared surface. The non-Arrhenius viscosity drop corresponds to the disappearance of the surface with the highest interaction energy between surface and free atoms (Pb(321) surface), while the non-Arrhenius viscosity rise corresponds to the disappearance of surface with the lowest interaction energy (Al(100) surface). All evidence indicates that the viscosity anomaly and the change of Wulff shape is closely related. The non-Arrhenius viscosity change in metallic melts is caused by the appearance/disappearance of certain surfaces of clusters, while the interaction strength of these surfaces determines the different features (non-Arrhenius drop/rise) of corresponding viscosity change.

Herb-symptom analysis of Erchen decoction combined with Xiebai powder formula and its mechanism in the treatment of chronic obstructive pulmonary disease.

Background: In recent years, the incidence and mortality rates of chronic obstructive pulmonary disease (COPD) have increased significantly. Erchen Decoction combined with Xiebai Powder (ECXB) formula is mainly used to treat lung diseases in traditional Chinese medicine (TCM). However, the active ingredients of ECXB formula, COPD treatment-related molecular targets, and the mechanisms are still unclear. To reveal its underlying action of mechanism, network pharmacology, molecular docking, and molecular dynamic (MD) simulation approaches were used to predict the active ingredients and potential targets of ECXB formula in treating COPD. As a result, Herb-Symptom analysis showed that the symptoms treated by both TCM and modern medicine of ECXB formula were similar to the symptoms of COPD. Network pharmacology identified 170 active ingredients with 137 targets, and 7,002 COPD targets was obtained. 120 targets were obtained by intersection mapping, among which the core targets include MAPK8, ESR1, TP53, MAPK3, JUN, RELA, MAPK1, and AKT1. Functional enrichment analysis suggested that ECXB formula might exert its treat COPD pharmacological effects in multiple biological processes, such as cell proliferation, apoptosis, inflammatory response, and synaptic connections, and ECXB formula treated COPD of the KEGG potential pathways might be associated with the TNF signaling pathway, cAMP signaling pathway, and VEGF signaling pathway. Molecular docking showed that ECXB formula treatment COPD core active ingredients can bind well to core targets. MD simulations showed that the RELA-beta-sitosterol complex and ESR1-stigmasterol complex exhibited higher conformational stability and lower interaction energy, further confirming the role of ECXB formula in the treatment of COPD through these core components and core targets. Our study analyzed the medication rule of ECXB formula in the treatment of COPD from a new perspective and found that the symptoms treated by both TCM and modern medicine of ECXB formula were similar to the symptoms of COPD. ECXB formula could treat COPD through multi-component, multi-target, and multi-pathway synergistic effects, providing a scientific basis for further study on the mechanism of ECXB formula treatment of COPD. It also provides new ideas for drug development.

In Silico Molecular Docking Simulation of Chromolaena Odorata Phytoconstituents Against Matrix Metalloproteinase Proteins – 9 (MMP-9)

The purpose of this study is to investigate the potential ligands of Chromolaena Odorata plants which contributes to the wound healing process. The ligands involved were phytol, ß-Caryophyllene, and 3,3-Dimethyl-1,2,4-cyclopentanetrione. This work addressed molecular docking simulations between the chosen ligands and Matrix Metalloproteinases (MMP) as the primary viral protein/receptor. The binding modes of the protein-ligand interactions were analysed. 9 poses of docking modes were obtained from the simulation. The ligand-receptor with the lowest interaction energy is the potential candidate for wound healing treatment. In summary, 3,3-Dimethyl-1,2,4-cyclopentanetrionehas been chosen to be the best docked complexes as it shows the lowest energy among the other ligands with value of -7.1 kcal/mol.

Unraveling the Role of Scutellaria baicalensis for the Treatment of Breast Cancer Using Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation.

Scutellaria baicalensis is often used to treat breast cancer, but the molecular mechanism behind the action is unclear. In this study, network pharmacology, molecular docking, and molecular dynamics simulation are combined to reveal the most active compound in Scutellaria baicalensis and to explore the interaction between the compound molecule and the target protein in the treatment of breast cancer. In total, 25 active compounds and 91 targets were screened out, mainly enriched in lipids in atherosclerosis, the AGE-RAGE signal pathway of diabetes complications, human cytomegalovirus infection, Kaposi-sarcoma-associated herpesvirus infection, the IL-17 signaling pathway, small-cell lung cancer, measles, proteoglycans in cancer, human immunodeficiency virus 1 infection, and hepatitis B. Molecular docking shows that the two most active compounds, i.e., stigmasterol and coptisine, could bind well to the target AKT1. According to the MD simulations, the coptisine-AKT1 complex shows higher conformational stability and lower interaction energy than the stigmasterol-AKT1 complex. On the one hand, our study demonstrates that Scutellaria baicalensis has the characteristics of multicomponent and multitarget synergistic effects in the treatment of breast cancer. On the other hand, we suggest that the best effective compound is coptisine targeting AKT1, which can provide a theoretical basis for the further study of the drug-like active compounds and offer molecular mechanisms behind their roles in the treatment of breast cancer.

Small, Electron-Donating Substituents Give CO2 Activation by Permethylpentalene Zirconium Amido Complexes the Upper Hand: A DFT Study of Distortion and Interaction

An insight into factors controlling CO2 activation is necessary to develop molecular systems that utilize CO2 as a chemical feedstock. Two permethylpentalene zirconium cyclopentadienyl (mono)amido complexes, Pn*ZrCp(NR2), were previously assessed for CO2 activation, and a strong dependence on the amido substituent was observed. The R = Me analogue reacted rapidly and quantitatively at room temperature to form the carbamato complex, while the R = Ph species was inert. Here, we investigate the origin of this reactivity difference using DFT and the distortion-interaction model to characterize steric and electronic contributions to the activation barrier. We find that the barrier for CO2 insertion with R = Me (19.1 kcal/mol) is lower than with R = Ph (36.6 kcal/mol), explaining the inertness of the Ph-substituted analogue. The distortion energy trend follows the steric bulk of the amido substituents, and the bulkier Ph-substituted complex has a consistently higher distortion energy along its potential energy surface than that of the Me-substituted complex. The interaction energy trend follows the electronics, and a more electron-donating Me-substituted complex shows a consistently lower interaction energy. The balance of these effects at the corresponding TS gives a reduced activation barrier. Small, electron-donating substituents therefore facilitate CO2 activation in these complexes.

Enhancing effect of choline chloride-based deep eutectic solvents with polyols on the aqueous solubility of curcumin–insight from experiment and theoretical calculation

The development of green solvents for enhancing aqueous solubility of drug curcumin remains a challenge. This study explores the enhancing effect of deep eutectic solvents (DESs) on the aqueous solubility of curcumin (CUR) via experiment and theoretical calculation. Choline chloride-based DESs with polyols 1,2-propanediol (1,2-PDO), 1,3-propanediol, ethylene glycol, and glycerol as hydrogen bond donors were prepared and used as co-solvents. The CUR aqueous solubility increased with increasing the DESs content at temperature of 303.15–318.15 K, especially in aqueous ChCl/1,2-PDO (mole ratio 1:4) solutions. The positive apparent molar volume values and reduced density gradient analysis confirmed the existence of strong interactions between CUR and solvent. The van der Waals interactions and hydrogen bonding coexisted in DESs monomer retained the stability of DESs structure after introducing CUR. Moreover, the lower interaction energy of DESs⋅⋅⋅CUR system than that of the counterpart DESs further proved the strong interaction between CUR and DESs. The lowest interaction energy of ChCl/1,2-PDO⋅⋅⋅CUR system indicated that this system was the most stable and ChCl/1,2-PDO was promising for CUR dissolution. This work provides efficient solvents for utilizing curcumin, contributing to a deep insight into the interactions between DES and CUR at the molecular level, and the role of DESs on enhancing drugs solubility.

Investigation of Oil–Water Separation on an F-SiO2/TiO2-Based Superhydrophobic/Superoleophilic Surface: Experiment Evaluation and MD Simulation

Experiment evaluation and mechanism analysis of separation performance are crucial for oily wastewater treatment. In this work, a fluorinated superhydrophobic/superoleophilic (F-SHPB/SOPL) surface was fabricated on a steel mesh substrate by double depositions of SiO2-TiO2 nanoparticles for high-roughness improvement and composite modification of fluorine-alkyl groups for low-energy achievement. Measurements of SEM, XPS, FTIR, laser scanning confocal microscope (LSCM), and excitation-emission matrix (EEM) were carried out for surface property characterization. The oil-water separation performances at the prepared F-SHPB/SOPL surface were investigated from experimental and simulation aspects. Separation tests, flux tests, and anti-contamination tests were performed by experimental methods. The results indicated that the surface showed excellent separation efficiencies (>99.2%) for oil-water mixture and oil-in-water emulsion, high permeate flux (>3000 L·m-2·h-1) for organic oils, and perfect anti-pollution/self-cleaning capacity for liquid and solid contaminations. The interaction energies and interaction distances were measured by ab initio molecular dynamics simulation (AIMD) simulations. With lower interaction energy (Eoil = -456.52∼-1044.22 eV) than that of water molecules (Ewater = -172.73 eV) and shorter distance (Doil = 4.42∼5.13 Å) than that of water molecules (Dwater = 11.49 Å), oil molecules showed higher interaction stability than water molecules on the F-SHPB/SOPL surface. The calculation revealed the essence of the oil-water separation phenomenon. This work not only proposes the fabrication methodology of the SHPB/SOPL material but also elucidates the intermolecular interaction for oil-water separation. The results can provide a fundamental basis for separation operation and removal treatment in industrial and domestic applications.

Phosphate-solubilizing microorganisms regulate the release and transformation of phosphorus in biochar-based slow-release fertilizer

Coupling phosphate-solubilizing microorganisms (PSM) can improve the availability of phosphorous (P) in biochar-based slow-release P fertilizers (BPF). However, the mechanism in release and transformation of P in BPF regulated by PSM is still unclear. Herein, the biocompatibility and the adhesion behaviors of BPF and PSM (Enterobacter hormaechei Rs-198) in soil were firstly studied, and a 90 days' laboratory-scale soil incubation experiment of BPF and Rs-198 was performed to study the transformation of P of BPF. The results show that BPF has a good biocompatibility for Rs-198 due to its low aromaticity, graphitization and free radicals' content (0.084 mg/g). Rs-198 are adhered to the surface of BPF in soil due to the high negative secondary energy minimum and low total interaction energy between Rs-198 and BPF. Available P in the incubation of BPF and Rs-198 (BR treatment) is significantly higher than that of the incubation of BPF (BF treatment) at initial 60 days. However, the content of available P in BR treatment is much lower compared with that in BF treatment on day 90, which is attributed to the entrapment of released P from BPF by Rs-198 and the formation of polyphosphate (polyP) rather than bound with soil mineral. Overall, this study presents new insights into the transformation of P in BPF regulated by PSM.

Exploring π-π interactions and electron transport in complexes involving a hexacationic host and PAH guest: a promising avenue for molecular devices.

Single isolated molecules and supramolecular host-guest systems, which consist of π-π stacking interactions, are emerging as promising building blocks for creating molecular electronic devices. In this article, we have investigated the noncovalent π-π interaction and intermolecular electron charge transport involved in a series of host-guest complexes formed between a cage-like host (H6+) and polycyclic aromatic hydrocarbon (PAH) guests (G1-G7) using different quantum chemical approaches. The host (H6+) consists of two triscationic π-electron-deficient trispyridiniumtriazine (TPZ3+) units that are bridged face-to-face by three ethylene-triazole-ethylene. Our theoretical calculations show that the perylene and naphthalene inclusion complexes G7⊂H and G1⊂H have the highest and lowest interaction energies, respectively. In addition, energy decomposition analysis (EDA) indicated that the dispersion interaction term, ΔEdisp, significantly contributes to the host-guest interaction and is correlated with the existence of π-π van der Waals interaction. Using the nonequilibrium Greens function (NEGF) method in combination with density functional theory (DFT), the current-voltage (I-V) curves of the complexes were estimated. The conductance values increased when the guests were embedded inside the host cavity. Notably, the complex G7⊂H has the maximum conductance value. Overall, this study provided the electron transport of the PAH inclusion host-guest complex through π-π interaction and provided a direction for the fabrication of future supramolecular molecular devices.

Quantum dot (Aun/Agn, n = 3-8) capped single lipids: interactions and physicochemical properties.

Realizing the potential of nano-hybrid biomaterials in various applications (nanoprobes to drug delivery), special attention has been devoted towards their synthesis and development. Nonetheless, several questions pertaining to the interface chemistry between the constituent entities (biomolecules and organic/inorganic part) of these hybrids, still remain unresolved. Keeping these unsolved issues in mind, the present theoretical investigation focuses on determining the electronic/physicochemical properties and interactions within gold and silver quantum dot-capped single lipid molecules. Quantum dots of varying sizes and shapes have been chosen and then coupled with lipid molecules (1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE), 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol, sodium salt (DMPG)), at the choline/glycerol, carboxylate and phosphate site. It has been identified that Au Qds interact strongly as compared to Ag clusters. In addition to the type, the shape and size of the Qd also influences their attachment with lipids. Among various sites, the phosphate site provides a considerably stronger platform for the coupling of Qds. On the other hand, attachment at the choline site leads to significantly lower interaction energies. The trend noted in interaction energies coincides with the structure-electronic property analysis (interatomic bond distances, charge transfer, PO2- stretching frequencies), which further helps in deducing the nature of interactions. The molecular dynamics simulations performed on selected Qd-lipid complexes established that the Qd interacting with lipids at the phosphate site remains fairly stable at room temperature without undergoing fragmentation into individual components. On the other hand, at the choline site, the Qd-to-lipid coupling is unstable and therefore they experience disintegration at 300 K temperature. Additionally, a unique glycerol-to-phosphate site crossover is evidenced, which reaffirms that the phosphate site is selectively preferred by Qds for binding with lipid molecules.

ZIM, a Norbornene Derived from 4-Aminoantipyrine, Induces DNA Damage and Cell Death but in Association Reduces the Effect of Commercial Chemotherapeutics

Cancer incidence is increasing, and the drugs are not very selective. These drugs cause adverse effects, and the cells become resistant. Therefore, new drugs are needed. Here, we evaluated the effects of ZIM, a candidate for chemotherapy, and 4-AA alone and in association with commercial chemotherapeutic agents. Subsequently, the results of ZIM and 4-AA were compared. Male Swiss mice were treated with doses of 12, 24, or 48 mg/kg ZIM or 4-AA alone or in association with cisplatin (6 mg/kg), doxorubicin (16 mg/kg), and cyclophosphamide (100 mg/kg). Biometric parameters, DNA damage (comet and micronuclei), cell death, and splenic phagocytosis were evaluated. DNA docking was also performed to confirm the possible interactions of ZIM and 4-AA with DNA. 4-AA has been shown to have low genotoxic potential, increase the frequency of cell death, and activate phagocytosis. ZIM causes genomic and chromosomal damage in addition to causing cell death and activating phagocytosis. In association with chemotherapeutical agents, both 4-AA and ZIM have a chemopreventive effect and, therefore, reduce the frequency of DNA damage, cell death, and splenic phagocytosis. The association of 4-AA and ZIM with commercial chemotherapeutic agents increased the frequency of lymphocytes compared to chemotherapeutic agents alone. Molecular docking demonstrated that ZIM has more affinity for DNA than 4-AA and its precursors (1 and 2). This was confirmed by the lower interaction energy of the complex (-119.83 kcal/mol). ZIM can break the DNA molecule and, therefore, its chemotherapeutic effect can be related to DNA damage. It is considered that ZIM has chemotherapeutic potential. However, it should not be used in combination with cisplatin, doxorubicin, and cyclophosphamide as it reduces the effects of these drugs.

Efficient in vivo and in silico assessments of antiandrogenic potential in zebrafish

This study aimed to establish zebrafish-based in vivo and in silico assay systems to evaluate the antiandrogenic potential of environmental chemicals. Zebrafish embryos were exposed to 17α-methyltestosterone (TES) alone or coexposed to TES and representative antiandrogens including flutamide, p,p′-DDE, vinclozolin, fenitrothion, and linuron. We assessed the transcript expression of the androgen-responsive gene sulfotransferase family 2, cytosolic sulfotransferase 3 (sult2st3). The expression of sult2st3 was significantly induced by TES in the later stages of embryonic development. However, the TES-induced expression of sult2st3 was inhibited by flutamide in a concentration-dependent manner (IC50: 5.7 μM), suggesting that the androgen receptor (AR) plays a role in sult2st3 induction. Similarly, p,p′-DDE, vinclozolin, and linuron repressed the TES-induced expression of sult2st3 (IC50s: 0.35, 3.9, and 52 μM, respectively). At the highest concentration tested (100 μM), fenitrothion also suppressed sult2st3 expression almost completely. Notably, p,p′-DDE and linuron did not inhibit sult2st3 induction due to higher concentrations of TES; instead, they potentiated TES-induced sult2st3 expression. Fenitrothion and linuron, which had relatively low antiandrogenic potentials in terms of sult2st3 inhibition, induced broader toxicities in zebrafish embryos; thus, the relationship between developmental toxicities and antiandrogenic potency was unclear. Additionally, an in silico docking simulation showed that all five chemicals interact with the zebrafish AR at relatively low interaction energies and with Arg702 as a key amino acid in ligand binding. Our findings suggest that a combination of zebrafish-based in vivo and in silico assessments represents a promising tool to assess the antiandrogenic potentials of environmental chemicals.