Search Results (246)

In order to explore the essence of the anticoccidiosis of anticoccidial drugs under bioelectric currents, the intermolecular double-proton transfer and conformational transformation of 4-pyridone-3-carboxylic acid were investigated by quantum chemistry calculations (at the M06-2X/6-311++G**, M06-2X/aug-cc-pVTZ and CCSD(T)/aug-cc-pVTZ levels) and finite temperature string (FTS) under external electric fields. The solvent effect of H₂O on the double-proton transfer was evaluated by the integral equation formalism polarized continuum model. The results indicate that the influences of the external electric fields along the direction of the dipole moment on double-proton transfer are significant. The corresponding products are controlled by the direction of the external electric field. Due to the first-order Stark effect, some good linear relationships form between the changes of the structures, atoms in molecules (AIMs) results, surface electrostatic potentials, barriers of the transition state, and the external electric field strengths. From the gas to solvent phase, the barrier heights increased. The spatial order parameters (ϕ, ψ) of the conformational transformation could be quickly converged through the umbrella sampling and parameter averaging, and thus the free-energy landscape for the conformational transformation was obtained. Under the external electric field, there is competition between the double-proton transfer and conformational transformation. The external electric field greatly affects the cooperativity transfer, while it has little effect on the conformational transformation. This study is helpful in the selection and updating of anticoccidial drugs. Full article

The title compound, C₂₆H₂₁BrN₂O₅ (Compound 4), was obtained via our previously described procedure with modifications, i.e., via a facile one-pot three component reaction starting from commercially available materials. Compound 4 was crystallized from nitromethane. It crystalized in a triclinic crystal system, in the P-$\overline{1}$ space group. The crystal structure of 4 is described herein. Hirsfeld surface analysis, generated by the Crystal Explorer 21 software, was used to visualize the intermolecular close contacts in the title compound. The electrostatic, dispersion, and total energies in the crystal structure were calculated using the same program. Full article

This research represents the first application of the MOLS method to characterize the conformational energy landscape of an antimicrobial peptide within a solvent environment, providing a novel approach to understanding peptide behavior in solution. This method’s exhaustive nature ensures that all minimum-energy conformations for a given amino acid sequence are sampled. In this work, we employed a combination of MOLS and VMD software to generate structural models of a cyclic peptide, both solvated and non-solvated, and then utilized the CHARMM force field to conduct energy calculations throughout the sampling process. In the presence of a solvent, this method predicted a structure close to the experimental crystal structure. A significant reduction was observed in gamma turn motifs in the presence of water. The solvent molecules also favored different hydrogen bonding patterns in the peptide by orchestrating an intermolecular interaction with the peptide atoms. This intermolecular interaction involves an ARG side chain and further stabilizes the backbone. It is evident that solvent interactions are key in designing antimicrobial peptides. This study will help in designing and understanding peptides for use as therapeutic agents like antibacterial or antimicrobial peptides. Each conformer obtained from the MOLS method would be one of the best starting points for molecular dynamic simulation to further explore the landscape. Full article

The substituent effects on crystal stacking topology and stability of the 5,5-dinitro-2H,2H-3,3-bi-1,2,4-triazole (DNBT) and its three energetic cocrystals with 1,3,5-trinitrobenzene (TNB), 2,4,6-trinitrotoluene (TNT), and picric acid (PA) were systematically investigated through combined density functional theory (DFT) calculations and classical molecular dynamics (MD) simulations. The interaction mechanism and detonation performance of the three energetic cocrystals were implemented to the electrostatic potential (ESP), Hirshfeld surface analysis, radial distribution function (RDF), binding energy, and detonation parameters. In contrast to N-H⋯O interactions in DNBT, three cocrystals exhibited more distinctly weak C-H⋯O intermolecular hydrogen bonds and NO₂-π stacking interactions to stabilize the lattice. Notably, the highest binding energy of PA/DNBT shows the largest stability and lowest impact sensitivity is related to the more intermolecular interactions. Although the introduction of substituents slightly affects the crystal density of DNBT crystals, it significantly reduces the impact sensitivity. Moreover, the balanced detonation performance and impact sensitivity of DNBT-based cocrystals make it a candidate to expand the applications of DNBT crystals. These findings contribute to a broadened understanding of construction and design strategies for the energy release mechanisms of energetic compounds with the azoles ring family. Full article

A brief summary of the effect of nonspecific interactions upon chemical equilibria in solutions containing a high total concentration of macromolecular solutes comparable to that found in biological fluid media is presented. Analyses of experimental measurements permitting relatively direct quantitation of the free energy of nonspecific intermolecular interaction in solutions of one or two macrosolutes are described, and a table listing published experimental studies of both homo- and hetero-interactions is provided. Methods for calculating the free energy of nonspecific interaction via theory and computer simulation are described. Recommendations for further progress in both measurement and calculation of interaction free energies are presented. Full article

Dormancy occurs when Mycobacterium tuberculosis (Mtb) enters a non-replicating and metabolically inactive state in response to hostile environment. During this state, it is highly resistant to conventional antibiotics, which increase the urgency to develop new potential drugs against dormant bacilli. In view of this, the dormancy survival regulator (DosR) protein is thought to be an essential component that plays a key role in bacterial adaptation to dormancy during hypoxic conditions. Herein, the NP-lib database containing natural product compounds was screened virtually against the binding site of the DosR protein using the MTiopen screen web server. A series of computational analyses were performed, including redocking, intermolecular interaction analysis, and MDS, followed by binding free energy analysis. Through screening, 1000 natural product compounds were obtained with docking energy ranging from −8.5 to −4.1 kcal/mol. The top four lead compounds were then selected for further investigation. On comparative analysis of intermolecular interaction, dynamics simulation and MM/GBSA calculation revealed that M3 docked with the DosR protein (docking score = −8.1 kcal/mol, RMSD = ~7 Å and ΔG Bind = −53.51 kcal/mol) exhibited stronger stability than reference compound Ursolic acid (docking score = −6.2 kcal/mol, RMSD = ~13.5 Å and ΔG Bind = −44.51 kcal/mol). Hence, M3 is recommended for further validation through in vitro and in vivo studies against latent tuberculosis infection. Full article

The avian influenza virus, particularly the highly pathogenic H5N1 subtype, represents a significant public health threat due to its interspecies transmission potential and growing resistance to current antiviral therapies. To address this, the identification of novel and effective neuraminidase (NA) inhibitors is critical. In this study, an integrated in silico strategy was employed, beginning with the generation of an energy-optimized pharmacophore model (e-pharmacophore, ADDN) based on the reference inhibitor Zanamivir. A virtual screening of 47,781 natural compounds from the PubChem database was performed, followed by molecular docking validated through an enrichment assay. Promising hits were further evaluated via ADMET predictions, density functional theory (DFT) calculations to assess chemical reactivity, and molecular dynamics (MD) simulations to examine the stability of the ligand–protein complexes. Three lead compounds (C1: CID 102209473, C2: CID 85692821, and C3: CID 45379525) demonstrated strong binding affinity toward NA. Their ADMET profiles predicted favorable bioavailability and low toxicity. The DFT analyses indicated suitable chemical reactivity, particularly for C2 and C3. The MD simulations confirmed the structural stability of all three ligand–NA complexes, supported by robust and complementary intermolecular interactions. In contrast, Zanamivir exhibited limited hydrophobic interactions, compromising its binding stability within the active site. These findings offer a rational foundation for further experimental validation and the development of next-generation NA inhibitors derived from natural sources. Full article

Measurements of the surface tension of aqueous solutions of some trisiloxane surfactants containing various polyether groups (HOL7, HOL9, and HOL12) at 293 K, 303 K, and 313 K were performed. The studied surfactants were synthesized by hydrosilylation reaction and their structural analysis was carried out by the ¹H NMR, ¹³C NMR, ²⁹Si NMR, as well as FT-IR techniques. The thermal stability of HOL7, HOL9, and HOL12, as well as their molecular weight distributions, were also studied. On the basis of the obtained experimental results of the surface tension of aqueous solutions of HOL7, HOL9, and HOL12, the activity of the studied surfactants at the water–air interface was determined and discussed in the light of intermolecular interactions. Using the measured values of the surface tension, the Gibbs surface excess concentration, the area occupied by the surfactant molecule in the adsorption layer, and the standard Gibbs free energy of adsorption of the studied surfactants at the water–air interface were also calculated. Based on the obtained thermodynamic parameters of adsorption of the studied surfactants at the water–air interface, temperature, as well as a number of polyether groups in the hydrophilic part of surfactant, impact on particular surfactant adsorption was deduced. In general, the changes in the standard Gibbs free energy of adsorption of the studied surfactants at the water–air interface indicate that their adsorption tendency decreases with decreasing temperature. In addition, that tendency also diminishes as the number of the polyether groups in the hydrophilic part of the surfactant increases. Full article

This article discloses the synthesis of four new positional isomeric zwitterionic ligands exhibiting semi-flexible and flexible characteristics—n-pyridinium-1,2,3-triazole-4-carboxy-5-Acetate (n-PTCA), and n-methylpyridinium-1,2,3-triazole-4-carboxy-5-Acetate (n-MPTCA; where n = 3, 4)—which were derived from an aqueous solution of the corresponding sodium salts in an acidic medium (HCl). These compounds are successfully synthesized and characterized with FT-IR and multinuclear NMR spectroscopy; likewise, proper single crystals are obtained for each compound. All compounds adopt zwitterionic forms in the solid state, which are stabilized via intermolecular proton transfer processes involving HCl and solvent molecules. A single-crystal X-ray analysis revealed how positional isomerism and molecular flexibility influence the supramolecular topology. Specifically, 3-PTCA and 4-PTCA exhibit isomorphic hydrogen bond networks, while 3-MPTCA and 4-MPTCA display distinct packing motifs, attributed to the presence of a methylene spacer between the pyridinium and triazole rings. The Hirshfeld surface analysis quantitatively confirmed the dominance of O···H/H···O and N···H/H···N interactions in the solid-state architecture. These strong hydrogen-bonding networks are indicative of the potential proton-conductive behavior in the crystalline state, positioning these compounds as promising candidates for applications in proton-conducting materials. The structural insights gained underscore the pivotal role of molecular topology in tailoring crystal packing, with implications for the rational design of zwitterionic ligands in functional materials, including MOFs and coordination polymers. The calculated HOMO-LUMO energy gaps reveal a significant electronic variability among the ligands, influenced primarily by the positional isomerism and structural flexibility introduced by the methylene spacer. Full article

Background: Casein kinase 1 epsilon (CK1ε) plays a critical role in cancer progression by activating oncogenic signaling pathways, making it a target for cancer therapy. However, no inhibitors are currently available for clinical use, highlighting the need for novel therapeutic candidates. Methods: This study aimed to identify potential CK1ε inhibitors. To achieve this, a modified version of a previously reported pharmacophore model was applied to an ultra-large database of over 100 million compounds for virtual screening. Hits were filtered based on drug-likeness and pH-dependent pharmacophore compliance and then grouped according to their structural core. A representative compound from each structural group underwent molecular dynamic (MD) simulations and binding free energy calculations to predict its stability and affinity, allowing extrapolation of the results to the entire set of candidates. Results: Pharmacophore matching initially identified 290 compounds. After energy minimization, and an assessment of drug-likeness and pharmacophore compliance, we selected 29 structurally related candidates. MD simulations showed that most of the compounds representative of structural groups had stable binding modes, favorable intermolecular interactions, and free energies comparable to those of previously reported CK1ε inhibitors. An analysis of additional members of the most promising structural group showed that two 2,4-diaminopyrimidine-based compounds likely inhibit CK1ε. Conclusions: These findings provide structural insights into the design of CK1ε inhibitors, supporting compound optimization and the eventual development of targeted cancer therapeutics. Full article

Laccases are versatile enzymes capable of oxidizing a wide variety of antibiotics. In this study, the mechanism of catalytic oxidation of first-generation tetracyclines, namely, oxytetracycline, tetracycline, and chlortetracycline, by the Melanocarpus albomyces laccase enzyme was investigated using molecular docking and DFT calculations. Molecular docking studies revealed that all three substrates exhibit negative interaction energies, indicating stable enzyme–substrate complexes, with tetracycline and chlortetracycline showing the highest binding affinities. Global reactivity indices obtained by DFT confirmed the high electrophilicity of the enzyme active site, particularly the aminoacidic residues Glu235 and His508, favoring electron transfer from the substrates. In addition, NBO analysis allowed quantification of the energy of hydrogen bonds in enzyme–substrate interactions, evidencing their key role in the stabilization of the complex. Proton transfer analysis suggested two possible mechanisms: (1) a direct concerted transfer and (2) a process mediated by water molecules. The results provide insights into the thermodynamics, electronic structure, and nature of intermolecular interactions governing the oxidation of tetracyclines by the enzyme, highlighting their potential in bioremediation strategies for antibiotic degradation. Full article

In this study, we employed density functional theory (DFT), a standard method in quantum chemistry, to investigate the structural intricacies of thioether-linked naphthalene-based liquid-crystal dimers. The theoretical analysis included the calculation of the molecular bend angle, a crucial factor influencing the formation of the twist–bend nematic (N_TB) phase, as well as other molecular parameters such as transition dipole moments, bond lengths, and bond energies. These calculations allowed for the determination of the probable conformations and the computation of their vibrational spectra, which are essential for interpreting experimental spectra. Connecting these insights, we identified stable conformations and observed differences in the spectra between the conventional nematic (N) and N_TB phases. The combined DFT calculations and infrared absorbance measurements allowed us to investigate the structure and intermolecular interactions of molecules in the N and N_TB phases of the dimers. Notably, significant changes in average absorbance were detected in the experimental spectra in the N_TB phase. During the transition from the N phase to the N_TB phase, a clear decrease in absorbance for longitudinal dipoles and an increase for transverse dipoles were observed. This phenomenon suggests that longitudinal dipoles are antiparallel, while transverse dipoles are parallel. To verify the influence of nearest-neighbor interactions, DFT calculations were conducted on a system comprising several neighboring molecules. Full article

Dicyanovinyl (DCV)-substituted oligothiophenes consist of both electron donor and acceptor ligands, which makes them promising materials for organic electronics. Here, we studied the structural and electronic properties of methyl-substituted dicyanovinyl-quinquethiophenes (DCV5T-Me₂) adsorbed on different metal surfaces, namely Au(111), Ag(111), and Cu(111), by using low-temperature scanning tunneling microscopy/spectroscopy (STM/STS). It is found that the assembled structures of DCV5T-Me₂ and the corresponding electronic properties vary depending on the underlying substrates. On Au(111) and Ag(111), compact organic islands are formed through intermolecular hydrogen bonding and electrostatic interactions. The lowest unoccupied molecular orbital (LUMO) and LUMO+1 of DCV5T-Me₂ are lower in energy on Ag(111) than those on Au(111), due to the stronger molecule–surface interaction when adsorbed on Ag(111). Moreover, orbital distributions of the LUMO and LUMO+1 in dI/dV maps on Au(111) and Ag(111) are the same as the DFT-calculated orbital distributions in gas phase, which indicates physisorption. In contrast, chemisorption dominates on Cu(111), where no ordered assemblies of DCV5T-Me₂ could be formed and resonances from the LUMO and LUMO+1 vanish. The present study highlights the key role of molecule–substrate interactions in determining the properties of organic nanostructures and provides valuable insights for designing next-generation organic electronics. Full article

Bio-hybrid fuels, chemically derived from sustainable raw materials and green energies, offer significant potential to reduce carbon dioxide emissions in the transport sector. However, when these fuels are used as drop-in replacements in internal combustion engines, material compatibility with common sealing materials is not always given. Within the cluster of excellence, “The Fuel Science Center (FSC)” at RWTH Aachen, experimental immersion tests were conducted on a limited set of fuel and sealing material combinations. Given the extensive range of possible fuel and sealing combinations, a data-based machine learning prediction framework was developed and validated to pre-select promising fuel candidates. Due to the limited number of samples, preliminary results indicate a need to expand the database. Since experimental investigations are time-consuming and costly, this work explores faster physics-motivated data generation approaches by modeling molecular interactions between fuel and sealing materials. Two modeling scales are employed. One calculates the intermolecular distance using density functional theory. The other uses Hansen solubility parameters, representing an abstract modeling of intermolecular forces. Both approaches are compared, and their limitations are assessed. Including the generated data in the prediction framework improves its accuracy. Full article

Two-dimensional (2D) metal-halide perovskites with highly efficient room-temperature phosphorescence (RTP) are rare due to their complex structures and intricate intermolecular interactions. In this study, by varying the alkyl chain length in organic amines, we synthesized two 2D metal-halide perovskites, namely 4-POMACC and 4-POEACC, both of which exhibit significant RTP emission. Notably, 4-POMACC demonstrates a stronger green RTP emission with a significantly longer lifetime (254 ms) and a higher photoluminescence quantum yield (9.5%) compared to 4-POEACC. A thorough investigation of structural and optical properties reveals that shorter alkyl chains can enhance the optical performance due to reduced molecular vibrations and more effective exciton recombination. Computational calculations further show that the smaller energy gap between S₁ and T_n in 4-POMA facilitates intersystem crossing, thereby improving RTP performance. Based on their remarkable phosphorescence properties, we demonstrated their applications in information encryption. This work offers a novel design strategy that could inspire the development of next-generation RTP materials. Full article