Search Results (762)

In response to recent advances in computer-aided drug discovery (CADD) enabled by high-performance computing, computational approaches were employed to support and rationalize the investigation of a VEGFR-2-targeted anticancer candidate, combining molecular-level modeling with experimental validation. Initial in silico ADMET profiling and molecular docking were conducted to support the evaluation of drug-like properties and target engagement within a series of para-toluidine-based derivatives (1–14). The most biologically active compound was further evaluated through 100 ns molecular dynamics simulations and comprehensive DFT calculations to investigate binding stability and electronic characteristics. Based on a rational design strategy and supported by computational analyses, the compounds were synthesized and fully characterized using IR, MS, ¹H/¹³C NMR, and elemental analysis. Biological evaluation was performed against HepG-2, MCF-7, HCT-116, and normal WI-38 cells. Mechanistic studies included VEGFR-2 inhibition, wound-healing migration assays, cell-cycle distribution analysis, apoptosis assessment, and caspase-3 activation. Several derivatives exhibited micromolar cytotoxic activity, with compound 14 emerging as the most active against HepG-2 cells (IC₅₀ = 7.84 ± 0.5 µM), showing cytotoxic activity comparable to that of sorafenib (IC₅₀ = 9.18 ± 0.6 µM) and demonstrating favorable selectivity toward normal WI-38 cells (IC₅₀ = 67.75 ± 3.6 µM). Compound 14 showed moderate VEGFR-2 inhibitory activity (IC₅₀ = 0.55 µM), significant suppression of cell migration, pronounced G₀/G₁ cell-cycle arrest, and robust apoptosis induction supported by caspase-3 activation. Molecular docking and MD simulations supported a stable binding mode within the VEGFR-2 active site. This integrated framework highlights compound 14 as a selectively active VEGFR-2-oriented anticancer candidate scaffold with a favorable selectivity profile, supported by experimental and computational analyses, warranting further lead optimization. Full article

The utilization and chemical transformation of carbon dioxide remains a pressing problem in modern chemistry. Numerous experimental and theoretical studies have focused on the interaction of CO₂ with amines. In this work, quantum chemical density functional theory (DFT) calculations of equilibrium geometries, energies, electronic and vibrational characteristics of CO₂-sensitive mono-, di-, tris-hydroxyamidines and their associates were carried out by the B3LYP/6-31G(d, p) method. The harmonic vibrational frequencies were scaled and compared with the experimental FTIR spectra for supporting wavenumber assignments. Natural bond orbital (NBO) analysis of the atomic charges and charge delocalization was employed to investigate the nature of hydrogen bonding in hydroxyamidine associates. We also used the intrinsically polarizable continuum model (IEFPCM), and the DFT-D3 method was applied to account for dispersion effects during associate formation. Using the 6-311+G(2d, p) basis set for tris-hydroxyamidine, and its adducts, a comparative analysis of the experimental and calculated ¹H NMR spectra was performed. Here, we considered non-trivial sites of carbon dioxide absorption and hydroxyamidine protonation, which, to our knowledge, have hardly been considered by other authors. Present DFT results agree rather well with the experimental data and support new insight into the formation of the PIL structure. Full article

This study presents the synthesis and electrochemical characterization of meso-tetracyanobutadiene (TCBD)-functionalized diphenylporphyrin (DPP) complexes incorporating copper (Cu) and nickel (Ni) metals. These push–pull metallo diphenylporphyrin–TCBD complexes were synthesized via a [2 + 2] cycloaddition–retroelectrocyclization reaction between 5-bromo-15-formyl-10,20-diphenylporphyrin metal(II) complexes (M = Cu, Ni) and tributyl(phenylethynyl)stannate, followed by tetracyanoethylene (TCNE) addition. The resulting TCBD-functionalized porphyrins were obtained in moderate yields (70–75%) and thoroughly characterized by ¹H and ¹³C NMR, UV-Vis spectroscopy, MALDI-TOF-MS, and single-crystal XRD. Although the single-crystal X-ray structure of NiDPP was solved, DFT calculations were used to determine the structures of the donor–acceptor MDPP-TCBD systems and to visualize their electronic structures. HOMO on the porphyrin π system and LUMO on the TCBD entity were observed, and energy level diagrams clearly laid out the electron donor and acceptor parts of the molecular systems. As expected, these novel donor–acceptor porphyrinoid assemblies exhibited enhanced push–pull properties in both the ground and excited states. Femtosecond transient absorption studies revealed that both NiDPP-TCBD and CuDPP-TCBD populate the charge-transfer state upon photoexcitation, with lifetimes of 383.1 ps and 484.7 ps, respectively, in benzonitrile. The charge-transfer states populated the triplet or doublet states (in the case of CuDPP) before returning to the ground state. Full article

Naphthyridine derivatives have emerged as privileged scaffolds with diverse pharmacological activities, particularly in anticancer and antiviral drug discovery. In this study, a series of naphthyridine-based derivatives (1–10b) was designed, synthesized, and structurally characterized using IR, ¹H/¹³C NMR, and mass spectrometry, and evaluated as dual-function antiproliferative and anti-fowlpox virus agents supported by integrated computational analyses. The synthesized compounds were screened for in vitro antiproliferative activity against HeLa, HCT-116, and MCF-7 cancer cell lines, as well as normal WI-38 lung fibroblasts. Several derivatives exhibited potent cytotoxic activity with enhanced selectivity toward cancer cells. Compound 5b showed the highest activity against HeLa cells, compound 1 was most effective against HCT-116 cells, while compounds 7 and 8 displayed remarkable activity against MCF-7 cells, with compound 7 surpassing doxorubicin and compound 8 demonstrating excellent selectivity toward normal cells. Mechanistic investigations revealed that compounds 7 and 8 acted as dual topoisomerase I/IIβ inhibitors, inducing G2/M cell cycle arrest and intrinsic apoptosis associated with caspase-9 activation and downregulation of topoisomerase II protein expression. Selected derivatives were further evaluated for antiviral activity against fowlpox virus using in ovo and in vivo SPF embryonated chicken egg models, where compounds 2 and 9a exhibited the highest therapeutic indices, comparable to ribavirin, and compound 9a markedly suppressed viral replication and titers in vivo. ADMET profiling, molecular docking, molecular dynamics simulations, and DFT calculations supported the experimental findings and identified compound 10a as the most favorable theoretical candidate. Overall, this integrated experimental–computational approach establishes naphthyridine derivatives as a rationally designed multifunctional chemotype for simultaneous anticancer and antiviral drug development. Full article

In this work, the coordination compound sulfate of aqua{tris(2-pyridylmethyl) amine}zinc(II) ([Zn(TPA)(H₂O)]SO₄) is investigated as a catalyst for the molecular reduction of CO₂. The complex was synthesized and characterized by FT–IR, UV–Vis, TGA, and NMR spectroscopy. Cyclic voltammetry reveals irreversible electrochemical behavior, with two cathodic peaks at E_pc = −1.72 V and E_pc = −1.99 V vs. Fc/Fc⁺, respectively. Under a CO₂ atmosphere, a catalytic wave appears at E_pc = −1.87 V vs. Fc/Fc⁺, indicating catalytic activity toward CO₂ reduction. This behavior was further confirmed by Foot-of-the-Wave Analysis (FOWA), which yielded a catalytic rate constant of (k = 1.352 × 10³ M⁻¹ s⁻¹). Bulk electrolysis experiments combined with FT–IR analysis suggest that format is the main product of the CO₂ reduction catalyzed by [Zn(TPA)(H₂O)]SO₄. Electrochemical impedance spectroscopy was used to examine the catalytic process at the electrode–electrolyte interface. In addition, density functional theory (DFT) calculations were conducted to analyze the interaction between the [Zn(TPA)(H₂O)]SO₄ complex and CO₂. Full article

Developing molecular electrocatalysts with controllable and predictable properties remains a central challenge in hydrogen evolution reaction (HER) catalysis. Herein, four Sb(III) corrole complexes (1–4) bearing zero to three p-cyano-substituted meso-phenyl groups (-CN Ph) were synthesized to investigate the effect of electron-withdrawing substituents on their catalytic HER performance, in which complexes 2–4 are newly reported. All prepared complexes were well characterized via UV–vis, NMR, HRMS, and XPS. SEM–EDS and UV–vis analyses indicated their uniform dispersion and excellent stability under organic and neutral aqueous solvent electrolysis conditions. When using TsOH as the proton source in DMF, complex 4 exhibited the highest activity with a TOF of 42.19 s⁻¹ at an overpotential of 895 mV. In mixed aqueous–organic media, the Faradaic efficiency of complex 4 reached 85.5%. The HER activity increases with the increasing number of cyano groups, and this observation has been rationalized via DFT calculations, which indicates a ligand-centered reduction and supports a possible ECEC pathway for the HER. These results highlight that cyano functionalization can modulate the electronic properties of Sb(III) corroles, thereby enhancing HER performance. This is helpful for designing efficient Sb(III) corrole-based HER catalysts. Full article

The relative position of the oxime group within pharmaceutically relevant pyridinium oximes is a pivotal factor that governs their intrinsic physicochemical properties and their biological reactivity. However, studies providing in-depth, molecular-level insight into these structure–reactivity relationships are still limited. In this work, we present an integrated experimental and computational study of N-methylpyridinium-2-aldoxime chloride (PAM2-Cl), N-methylpyridinium-3-aldoxime iodide (PAM3-I), and N-methylpyridinium-4-aldoxime iodide (PAM4-I), aimed at elucidating discrete differences in their ionization behavior, electronic structure, σ-donor properties, and nucleophilicity. The crystal structure of PAM3-I was determined by X-ray diffraction. Comparative structural and spectroscopic (UV–Vis, NMR, IR) analyses elucidated the structural and electronic effects arising from the position of the oxime group. Kinetic studies of substitution reactions with aquapentacyanoferrate(II) in aqueous solution enabled the determination of pentacyano(PAM)ferrate(II) formation and dissociation rate constants, coordination modes, pK_a values of the coordinated ligands, complex stability constants, and σ-donating capabilities. The DFT-based analysis of atomic charge distribution transcended experimental limitations, offering a new perspective on electronic structure-related properties. This study presents the first side-by-side, internally consistent structure–reactivity map across PAM2, PAM3, and PAM4 isomers that triangulates crystallography, UV–Vis-derived pK_a values, substitution kinetics, and DFT descriptors in a single framework. Full article

The structural role of solvation phenomena in bioorganic compounds has been documented sporadically over the last two decades, although they are of fundamental importance in a variety of chemical, physical, and biological processes. NMR chemical shifts depend on the electron densities around the nuclei, which can be influenced by the surrounding environment. Solvent-dependent chemical shift variations, therefore, can provide important structural information on solute–solvent interactions, especially nuclei, which belong to polar groups, such as OH, NH, CONH, COOH, etc. Recent developments in quantum chemical methods for calculating NMR chemical shifts, especially those incorporating explicit solvent effects, and the exponential advances in computer power can provide an excellent methodology for the accurate calculation of chemical shifts in solution. Furthermore, comparison of density functional theory (DFT) calculated activation free energies with NMR experimentally determined values can provide a reliable method for investigating the role of solvents in various atomistic reaction mechanisms. It has been demonstrated that the combined use of NMR and DFT calculations represents the new frontier of our understanding of the role of solvents, at the atomic level, in molecular structures and in catalytic reactions of bioorganic molecules, natural products and model compounds. Full article

While advanced imaging techniques and ordered porous materials like MOFs have gained prominence, gas sorption remains the indispensable tool for characterizing the multiscale heterogeneity of industrially important disordered solids, such as catalysts and shales. This review examines recent developments in gas sorption methodologies specifically tailored for rigid, disordered porous media. We discuss experimental advances, including the choice of adsorbate and the utility of the overcondensation method for probing macroporosity and ensuring saturation. Furthermore, we critically evaluate theoretical approaches for determining pore size distributions (PSDs), contrasting classical methods with Density Functional Theory (DFT) and Grand Canonical Monte Carlo (GCMC) simulations. Special emphasis is placed on the impact of pore-to-pore cooperative effects, such as advanced condensation, cavitation, and pore-blocking, on the interpretation of sorption isotherms. We highlight how complementary techniques, including integrated mercury porosimetry, NMR, and computerized X-ray tomography (CXT), are essential for deconvolving these complex network effects and validating void space descriptors. We conclude that, while “brute force” molecular simulations on image-based reconstructions are progressing, “minimalist” pore network models, which incorporate cooperative mechanisms, currently offer the most empirically adequate approach. Ultimately, gas sorption remains unique in its ability to statistically characterize void spaces from Angstroms to millimeters in a single experiment. Full article

Here, we synthesized 2,3,4,6-tetra(9H-carbazol-9-yl)benzonitrile (4CzHPN) via visible-light-driven photocatalytic monodecyanation using the versatile metal-free catalyst 4CzIPN. Characterized by NMR, IR, X-ray diffraction, and DFT calculations, it features a 3.49 eV HOMO-LUMO gap and shows blue-shifted absorption/emission, emerging as a promising advanced metal-free photoredox catalyst. Full article

The use of styrylium dyes as organic nonlinear optical materials in many photonics domains has been the subject of research for decades. It has been noted that over time, research has also looked into the biological activity of styrylium dyes, namely their antibacterial effects, as well as attempts to establish links between structure and property by choosing particular structural pieces. These investigations’ scope is still very limited. Therefore, our main goal was to synthesize a styrylium compound with antimicrobial potential. A novel styrylquinolinium compound (D) was synthesized using Knoevenagel condensation. Spectroscopic techniques, including IR, 1D and 2D NMR (COSY, HSQC, and HMBC), HRMS spectra, and X-ray analysis, were used to confirm its structure. The antimicrobial and anti-inflammatory activity of the compound was assessed. The compound was found to have very good antimicrobial activity against five Gram-positive strains, three Gram-negative strains, and fungi. The most pronounced effect of the compound was against Escherichia coli and Pseudomonas aeruginosa. The compound’s anti-inflammatory activity was evaluated through its ex vivo immunohistochemistry. DFT calculations, such as geometry optimization, Molecular Electrostatic Potential (MEP), HOMO–LUMO, reactivity parameters and molecular docking simulation were applied to investigate the electronic features of the compound and confirm the biological activity. The compound (D) demonstrated a promising antibacterial and immunomodulatory profile. Its ability to induce IL-1β and at the same time moderately reduce NOS3 can be considered as a controlled adaptation of the immune response, especially in cases requiring local immune activation. Docking simulation revealed that (D) binds effectively to the active site of the bacterial protein, supporting the experimental findings of the compound’s antibacterial activity. Full article

The development of oxidation-resistant and regenerable materials remains a major challenge for mercury removal from contaminated waters and industrial effluents. In this study, a zwitterionic mesoporous silica gel functionalized with L-cysteine (SG-3PS-Cys) was synthesized, where the thiol group is covalently anchored to the silica framework, preventing oxidative degradation while preserving –NH₃⁺ and –COO⁻ groups for Hg(II) coordination. Spectroscopic analyses (FTIR, XPS, and ¹³C NMR) confirmed the formation of a stable, thiol-free binding environment in which mercury interacts through carboxylate oxygen atoms, electrostatically stabilized by neighboring ammonium groups. The material exhibited a high surface area (134 m² g⁻¹) and uniform mesoporosity (9.8 nm), achieving a maximum Hg(II) uptake of 82.7 mg g⁻¹ at pH 3 with rapid kinetics and cooperative S-type isotherms. The adsorbent retained 72% of its capacity after five regeneration cycles and maintained 38.7% selectivity toward Hg(II) in multicomponent solutions. DFT-based surface energy distribution analysis supported the zwitterionic coordination mechanism, revealing energetically homogeneous and high-affinity binding domains. Beyond its chemical stability, the material introduces a sustainable route for mercury remediation, linking surface energy, electrostatic effects, and porosity to achieve durable performance under acidic and complex aqueous conditions. These findings provide a mechanistic and design framework for the next generation of non-thiol adsorbents capable of selective and reusable Hg(II) removal in environmentally relevant scenarios. Full article

Background: Silver(I) complexes with aromatic heterocyclic ligands are well known for their broad antimicrobial potential, largely attributed to their ability to interact with biomolecular targets. Results and Discussion: In this study, a new polynuclear silver(I) complex with N-(3′-phenylpropyl)quinoxaline-2-carboxamide (pqx-2ca), [Ag(NO₃)(pqx-2ca)]_n, was synthesized. Its structure was confirmed by single-crystal X-ray diffraction and comprehensively characterized using NMR, IR, and UV–Vis spectroscopy, while its behavior in solution was further elucidated through density functional theory (DFT) calculations combined with spectral simulations. The complex demonstrated significantly enhanced antimycobacterial activity compared with the free ligand when tested against the avirulent Mycobacterium tuberculosis H37Ra, fast-growing model organisms M. smegmatis and M. aurum, as well as the nontuberculous species M. avium and M. kansasii. Experimental and docking studies confirmed stable binding of the complex to subdomain III of bovine serum albumin (BSA) and to the minor groove of DNA. Furthermore, docking to validated mycobacterial targets revealed inhibitory potential toward the InhA and MmpL3 proteins, with binding affinities comparable to those of standard inhibitors. Conclusions: These results highlight [Ag(NO₃)(pqx-2ca)]_n as a promising candidate for the development of silver-based antimycobacterial agents with a dual mechanism of action involving both DNA and protein targets. Full article

In the search for solutions to the global health threat posed by antimicrobial resistance, the development of new compounds is crucial. In this context, the in vitro testing of known indolizinoquinolinedione analogs 1–7 revealed that N,N-syn regioisomers are more active than N,N-anti regioisomers. In particular, compound 2 (ethyl 5,12-dihydro-5,12-dioxoindolizino[2,3-g]quinoline-6-carboxylate) exhibited the most significant activity against Bacillus subtilis, B. cereus, Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA) bacteria. The reported increased bioactivity of metal complexes and their ability to overcome drug resistance through metal coordination have induced the study of new metal complexes of compound 2. FT-IR spectroscopy combined with DFT-simulated spectra confirmed the C=O chelation in all Zn, Cu, and Mn complexes 8–10. ESI-MS isotopic cluster analysis and UV-Vis-derived Job’s plot provided significant evidence for 1:1 chelation. Finally, ¹H NMR data were correlated to the DFT-calculated charge distribution. Complexes 8–10 displayed similar activity against B. subtilis, although this was lower than that for 2, and there were comparable effects with 2 and vancomycin antibiotic against S. aureus. FTsZ protein as a potential target of B. subtilis and DNA gyrase of S. aureus and MRSA were studied by docking calculations, revealing a good correlation with the in vitro results. Full article

Background/Objectives: Leishmaniasis constitutes one of the most fatal parasitic diseases globally, adversely impacting the health of individuals residing in both intertropical and temperate zones. In these geographical areas, the administration of treatment is often inconsistent and largely ineffective with the available pharmaceuticals, as these exhibit more pronounced side effects than the therapeutic advantages they purport to provide. Methods: Consequently, the current investigation seeks to engage in molecular modeling of novel pharmacological candidates incorporating 1,2,3 disubstituted triazole moieties, coordinated with Cu^II metal centers, in pursuit of promising bioactive properties. Results: Two complexes were prepared and X-ray analysis revealed a comparable structural configuration surrounding the copper (II) atom. The planar square coordination geometry was elucidated through the assessment of the ${\tau }_4=0$ (tau four) parameters. The comprehensive characterization encompasses HRMS-ESI (+), NMR, elemental analyses, mid-infrared, and UV-vis spectroscopic techniques. Time-dependent density functional theory (TD-DFT) analyses will substantiate the findings obtained through UV-vis spectroscopy. Crucially, the biological assays against Leishmania (L.) amazonensis revealed that Complex 1 exhibited outstanding potency against the intracellular amastigote form, demonstrating a half-maximal inhibitory concentration (IC₅₀) of 0.4 µM. This activity was 6-fold higher than that of amphotericin B (IC₅₀ = 2.5 µM) and 33-fold higher than pentamidine (IC₅₀ = 13.3 µM). Furthermore, Complex 1 showed a promising selectivity index (SI = 9.7) against amastigotes, surpassing the reference drugs and meeting the criteria for a lead compound. While less active on promastigotes, both complexes demonstrated high stability in DMSO solution, a prerequisite for biological testing. Conclusions: These results unequivocally identify Complex 1 as a highly promising candidate for the development of new antileishmanial therapies, warranting further in vivo studies. Full article