Computational investigations of D-glucofuranose-based derivatives: DFT, MEP, NBO, ADMET, PASS, and molecular docking toward antidiabetic targets

According to reports, the bioactive thiourea derivative was prepared from the ethanol solutions of thiourea and chloro acetic acid in a 1:1 M ratio. DFT calculations of 2-Imino-4-oxo-1,3-thiazolidine hydrochloride (IOTH) were performed with the use of B3LYP and the 6-311+G(2d,p) basis set. Frontier molecular orbitals, mapped electrostatic potential (MEP) map, and nonlinear optical (NLO) properties of the IOTH were all assessed. The compound was tested for drug-likeness using Swiss ADME. UsingB. pasteurii(PDB ID: 4UBP), calculations for molecular docking were then performed on the geometry-optimized structure. In order to determine the complex’s stability and the interactions between ligands and the receptor, the complex was subjected to molecular dynamics (MD) simulations. According to the results, the first hyperpolarizability value (β0) was 7.459 × 10−24 esu. The large first hyper polarization rate theoretically supported its use in the design of NLO materials. The calculated HOMO–LUMO energy gap value of the IOTH was found to be 2.87 eV. The small HOMO–LUMO energy gap suggested that IOTH is a soft molecule with a high degree of chemical reactivity but poor kinetic stability. The molecular docking study showed that the best ligand pose energy for the IOTH was −101.35 kcal/mol whereas the standard drug (acetohydroxamic acid) was −64.29 kcal/mol. The results demonstrated that the ligand–receptor complex remained stable during the MD simulations due to high binding affinity toBacillus pasteurii urease. The Lipinski Rule of Five was not violated in any way in the studied compound. This demonstrated that it is bioavailable. During clinical trials, the compound attrition rates would be lower, and the drug would have a better chance of being commercialized.

In this study, we report the design, synthesis, and comprehensive characterization of (E)-N-((1H-pyrrolo[2,3-b]pyridin-4yl) methylene)-2-fluoro-5- (4H-1,2,4-triazol-4-yl)aniline (PTA), a novel Schiff base integrating three bioactive motifs— pyrrolo[2,3-b]pyridine, 1,2,4-triazole, and fluorinated aniline—linked through a conjugated azomethine group. PTA was synthesized via condensation of 2-fluoro-5-(4H-1,2,4-triazol-4- yl)aniline with 1H-pyrrolo[2,3-b]pyridine-4-carbaldehyde under mild reflux conditions, affording a yellow solid in 81% yield. Its molecular structure was confirmed using Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR), ultraviolet–visible spectroscopy (UV–Vis), and mass spectrometry. Density Functional Theory (DFT) analyses, including frontier molecular orbital (FMO) and molecular electrostatic potential (MEP) studies, revealed a HOMO–LUMO gap of 3.562 eV, indicating moderate kinetic stability, and identified regions favorable for electrophilic and nucleophilic interactions. Molecular docking with the sulfonylurea receptor SUR1 (PDB ID: 6PZI) demonstrated stable binding through hydrogen bonding, π–π stacking, and van der Waals interactions, highlighting PTA’s potential as an antidiabetic lead. The combined experimental and theoretical findings suggest that PTA’s conjugated framework and electronic properties may be exploited in medicinal chemistry and optoelectronic applications.

Repurposing sulfonamide drugs as anticancer ligands and understanding its properties through density functional theory.

Crystal growth, morphological, mechanical, spectroscopic studies, optical properties, molecular docking, ADME/T, Hirshfeld surfaces analysis and theoretical calculations of hybrid organic-inorganic phosphate compound

A macromonomer containing dual-lactone, MMDL, was characterized by thermal degradation kinetics and density functional theory (DFT) calculations. The frontier molecular orbitals, molecular structural geometry, molecular electrostatic potential (MEP) and electrostatic potential (ESP) maps were determined with the help of structure optimizations based on the DFT method with standard 3–21G* as a basis set that has polarization functions on the second row atoms only. The 3–21G* basis set comprises the same number of primitive Gaussian functions. The electronic properties, such as electron affinity, HOMO–LUMO energies, ionization energy, electronegativity, chemical potential, global hardness and softness, global electrophilicity were computed with the help of the DFT method. The MEP and ESP maps were determined to predict the reactive sites of the macromonomer. Finally, the activation energy and thermal degradation mechanism for the initial part of the decomposition process under non-isothermal conditions were determined from the thermogravimetric analysis by integral approximation methods. The decomposition activation energies of the macromonomer were computed with the help of Flynn–Wall–Ozawa, Coats–Redfern and Tang methods. The kinetic equations showed that the reaction mechanism was an R1 mechanism, which is a phase boundary-controlled reaction (one-dimensional movement) solid-state mechanism.

During the present study, the structural, vibrational, electronic and biological properties of the novel antagonist LY2157299 as a transforming growth factor-β (TGF-β) receptor I kinase inhibitor are explored by quantum-mechanical (QM) and molecular docking methods. The characterization of the title compound is done using FT-IR and UV-Vis spectroscopy methods. The above computations were carried out using density functional theory (B3LYP) method with 6-31+G(d,p) basis set. The frontier molecular orbitals (HOMO and LUMO) energies were used to calculate the global reactivity indices of the said compound. The results explored the stability, reactivity and bioactivity of the compound under study. To identify the nucleophilic and electrophilic sites in the said compound, the molecular electrostatic potential (MEP), electron localization function (ELF) and Mulliken charge distribution graphs were generated. The present paper further explains the ligand-protein interactions through molecular docking investigations. The results of the molecular docking studies indicate that the most important interactions between the ligand and protein are related to the residues His 285, Val 341, Lys 342, His 283 and Glu 284.

In this study, the structural, electronic, pharmacokinetic, and biological properties of molecule 2-(6-kloro-2-(4-klorofenil)imidazo[1,2-a]piridin-3-il)-N, N-dipropilasetamid (Alpidem), an imidazopyridine derivative anxiolytic known for its high BZ₁ (benzodiazepine-1) receptor affinity and low adverse effect profile, were comprehensively investigated by density functional theory (DFT) and in-silico methods. The alpidem molecule was optimized using the 6-311G(d, p) basis set with the B3LYP and B3PW91 methods; information on the stability and chemical reactivity of the structure was obtained via the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), molecular electrostatic potential (MEP) maps, natural bonding orbital (NBO) analysis, non-linear optical (NLO) properties, and Mulliken charge distributions. Comparative analysis of two different methods has shown that the results are consistent with each other and provide reliable data. In addition, the drug similarity, bioavailability score, bioactivity values, absorption, distribution, metabolism, and excretion (ADME) profiles of the Alpidem molecule were calculated, and it was determined that the Alpidem molecule has pharmacologically favorable properties. Within the scope of molecular docking analyses, its interactions with two different enzymes (PDB ID: 2Z5X and 4BDT) associated with Alzheimer’s disease were evaluated. The binding energy values obtained were − 8.00 kcal/mol (2Z5X) and − 9.60 kcal/mol (4BDT), respectively, and the strong binding affinity, especially with the 4BDT protein, suggests that Alpidem may be a potential inhibitor candidate in Alzheimer’s disease. This multi-level theoretical study demonstrates that Alpidem is a drug repurposing molecule not only as an anxiolytic but also in neurodegenerative diseases and provides important data that will shed light on experimental studies. The results of this multi-level theoretical study show that Alpidem is a drug repurposing molecule not only as an anxiolytic but also in neurodegenerative diseases and provides important data that will shed light on experimental studies.

In the current study, the molecular geometry, electronic characteristics, nonlinear optical (NLO) properties, and potential biological activity of 1,3-bis(4-methylphenyl)triazene (I) were investigated by a combination of experimental crystallographic data and density functional theory (DFT) calculations at the B3LYP/6-311++G(d,p) level. The optimized molecular geometry was in very good agreement with experimental X-ray data, with a low root-mean-square deviation (RMSD) of 0.106 Å, verifying the computational model. The molecule demonstrated high NLO activity, possessing a first-order hyperpolarizability roughly seven times larger than that of urea, and potential application in optoelectronic and photonic devices. Frontier molecular orbital (FMO) calculation demonstrated HOMO–LUMO energy gap of 5.6015 eV in the gas-phase indicating kinetic stability, and solvent-phase calculation indicated higher reactivity and polarity at high-dielectric conditions. Global reactivity descriptors and molecular electrostatic potential (MEP) mapping identified key electrophilic and nucleophilic sites, with implications for the charge distribution of the molecule and probable modes of interaction. Mulliken and natural population analyses (NPA) also revealed electronic behavior, NPA providing more chemically meaningful charge partitioning. Thermodynamic properties -entropy, enthalpy, and heat capacity- exhibited smooth temperature dependence, which established the thermal stability of the compound. Hirshfeld surface and 2D fingerprint plots of the crystal structure highlighted the dominant role played by van der Waals interactions in crystal packing. Molecular docking studies with the HER2 receptor (PDB ID: 3PP0) showed good binding affinity (-9.8 k cal mol⁻¹) with the aid of supporting hydrogen bonding and hydrophobic interactions with prominent amino acid residues, which reflected potential anticancer activity. Combined, the findings emphasize the exciting multifunctionality of I, whose potential uses range from materials science to being a lead scaffold in drug design, particularly for HER2-targeted anticancer drugs.

This study presents a comprehensive analysis of six isoxazolidine and isoxazoline derivatives, employing a multifaceted approach that integrates Density Functional Theory (DFT), AdmetSAR analysis, and molecular docking simulations to explore their electronic, pharmacokinetic, and anticancer properties. Utilizing DFT analysis with the B3LYP-D3BJ functional and the 6-311++G(d,p) basis set, molecular geometries were optimized, and vibrational frequencies in the IR spectrum were evaluated, offering insights into the molecular structure and stability of the pharmaceutical compounds. Electrostatic potential maps were analyzed to predict functional group reactivity and protein-substrate interactions. Frontier Molecular Orbital (FMO) analysis and Density of States (DOS) plots revealed varying stability levels among the compounds, with 1b, 2b, and 3b exhibiting slightly higher stability. Chemical potential and hardness analyses highlighted stronger binding affinity for compounds 1b and 2b, suggesting stronger potential interactions. AdmetSAR analysis predicted favorable human intestinal absorption (HIA) rates for all compounds, with compound 3b showing superior oral effectiveness. Molecular docking and dynamics simulations were conducted targeting the receptor (PDB: 1JU6). Molecular docking simulations confirmed the high affinity of these compounds towards the target protein 1JU6, particularly compound 3b, which exhibited the most favorable binding energy of -8.50 kcal/mol. Molecular dynamics simulations demonstrated the superior stability of ligand 3b over 1b and 5-FU over 100 ns, suggesting its potential for further study. The 3b-protein complex exhibited stability through hydrophobic and hydrogen bond interactions, with 3b demonstrating reduced solvent exposure compared to 1b and 5-FU. This study underscores the promising role of compound 3b in anticancer treatments, providing a solid foundation for future drug development and optimization efforts.

Nonfullerene acceptors (NFAs) with an acceptor-donor-acceptor-donor-acceptor (A-DA'D-A) molecular framework have attracted much attention due to their excellent performance. However, the modifications of terminal units of asymmetric Y6-based NFA with terminal groups of different orientations are still few, and its effects on photoelectrical properties are still not clear. In this work, based on asymmetric IPC-BEH-IC2F (showing better performance than Y6 in experiment) with terminal groups in different orientations, we systematically designed six new NFAs via halogen and CN substitutions on terminal groups. The molecular planarity, dipole moments, electrostatic potential maps and their fluctuations, frontier molecular orbitals, exciton binding energy, UV-vis spectra, and energy difference between the first singlet and triplet states of these NFAs are predicted using reliable density functional theory (DFT) and time-dependent DFT (T-DFT) calculations. The results show that with respect to prototype CN-F, Br-F, CN-Br, and CN-Cl exhibit comparable energy levels of the lowest unoccupied molecular orbital (LUMO), reduced energy gap (by at least 0.026 eV), Eb (by at least 0.002 eV), and ΔEST (by at least 0.009 eV) values, red shifts (by at least 2 nm) in the wavelengths of the main absorption peaks, and enhanced absorption (by at least 0.05 in total oscillator strength) in the visible to near-infrared regions, indicating their potential as outstanding asymmetric NFAs. This study offers valuable insights into the future design and optimization of NFAs featuring asymmetric terminal groups.

The theoretical molecular structure of Ethyl 2-(2-benzylidenehydrazinyl)-4-methyl-6-phenylpyrimidine-5-carboxylate (DHPM), a pyrimidine derivative containing the Schiff base structure, was investigated using the Gaussian 09 software program. The chemical structure and chemical reactivity of the compound were calculated using Density Functional Theory (DFT). Quantum chemical calculations were performed using DFT(B3LYP/6-311G(d,p)) and DFT(B3PW91/LANL2DZ) methods and basis sets. Using these two methods and basis sets, molecular electrostatic potential (MEP) maps of the DHPM compound were drawn. Charge transfer properties of DHPM compound were analyzed using HOMO and LUMO level energy analysis. The stability of molecules as a consequence of charge delocalization and hyperconjugative interaction was studied using NBO analysis. In this study, the relationship between Alzheimer's disease and Acetylcholinesterase (AChE) (PDB:6WUY) and Butyrylcholinesterase (BChE) (PDB: 6SAM) enzymes was evaluated by molecular docking. The molecular docking scores of in molecular docking analysis were found to be -7.76 (PDB ID: 6WUY) and -7.98 (PDB ID: 6SAM) kcal. Finally in the study, ADME analysis was performed to evaluate DHPM compound as a drug according to Lipinski's rules. As a result of the ADME analysis, we think that DHPM compound will be evaluated as a drug candidate since it complies with Lipinski's rules.

Decoding the new dimensions of leucodelphinidin as a dual antioxidant and anti-diabetic candidate: A DFT, docking and dynamics evaluation.

Synthesis, crystal structure, DFT study, in vitro and in silico molecular docking of novel bis (aroyl selenourea) derivatives

Synthesis, structural elucidation, and antibacterial activities of novel copper(II), cobalt(II), and nickel(II) complexes with a bidentate Schiff base ligand against pathogenic bacteria

Trans-[Cu (quin)2(EtOH)2], a new copper (II) complex, was characterized using a variety of computational techniques to explore its biological role in pharmacological applications. The computational methods included density functional theory (DFT), ADMET and molecular docking. The optimized geometrical parameters revealed that the plane containing the Cu ion and the Quinaldinate ligands was confirmed to be nearly planar. DFT findings suggest that the complex has a stable structure with a moderate band gap of 3.88 eV. Highest Occupied Molecular Orbital (HOMO) and the Lowest Unoccupied Molecular Orbital (LUMO) analysis revealed a planar surface intramolecular charge transfer from its donor sites, in the center, to its ends instead of the vertical plane. Two electron-rich regions were observed around the oxygen ions in the molecular electrostatic potential (MEP) map, which were expected to be the sites of molecular bonding and interactions with target proteins. Drug-likeness and pharmacokinetics parameters were determined to provide insight into the safety level of the studied compound. The ADMET (absorption, distribution, metabolism, excretion, and toxicity) results showed favorable pharmacological features, as evidenced by a high oral bioavailability and a low risk of toxicity. A molecular docking study was performed by fitting the copper complex into the active sites of target proteins for Bacillus cereus, Staphylococcus aureus, and Escherichia coli bacteria. The title complex had the strongest antifungal effect within the inhibitory zone of B. cereus with a strong binding affinity of -9.83 kcal/mol. Also, maximum activity was exhibited against S.aureus (-6.65 kcal/mol) compared to the other recently reported Cu complexes within the limits of the screened references. Docking studies implicated modest inhibitory activity against E. coli bacteria. The findings highlighted the compound's biological activities and identified it as a possible treatment drug for the bacteria B. cereus and S. aureus.