A new mixed-ligand copper(II) maleate complex, [Cu(H₂dpzpda)(mal)]·CH₄O, containing the neutral tridentate H₂dpzpda ligand and a bidentate maleate ligand (mal²⁻), was synthesized and comprehensively characterized by physicochemical methods. The molecular structure of the compound was determined by single-crystal X-ray diffraction analysis. It was shown that the Cu(II) ion is in a five-coordinate N3O2 environment formed by three nitrogen atoms of the ligand and two oxygen atoms of the maleate anion. The Cu–N bond lengths are 1.998(3) Å (Cu–N4), 2.028(3) Å (Cu–N1), and 2.074(3) Å (Cu–N6), while the Cu–O distances are 1.927(3) Å (Cu–O3) and 2.111(3) Å (Cu–O1), which are consistent with typical values for copper(II) complexes. The crystal structure is stabilized by a system of intermolecular hydrogen bonds, leading to the formation of a supramolecular organization. Single-crystal X-ray diffraction analysis revealed that the Cu(II) center is five-coordinate and adopts a distorted trigonal bipyramidal geometry, as indicated by the trigonality index (τ = 0.78). The EPR parameters (g⊥ > g∥ ≈ gₑ, where gₑ = 2.0023) are consistent with this coordination environment and support the localization of the unpaired electron in the dz² orbital.The synthesized copper(II) complex was characterized with particular emphasis on its electronic structure, intermolecular interactions, and biological targeting potential. DFT calculations revealed a HOMO–LUMO energy gap of 3.87 eV, indicating a balance between kinetic stability and chemical reactivity, with significant electrophilic character as supported by a global electrophilicity index of 1.84 eV. Hirshfeld surface analysis and fingerprint plots demonstrated that the crystal architecture is primarily stabilized by H···O (26.8%) and H···N (14.0%) hydrogen bonding, alongside localized but structurally significant π-π stacking interactions (enrichment ratio = 3.10). Molecular Electrostatic Potential (MEP) mapping further identified nucleophilic oxygen sites and electrophilic nitrogen regions, providing a spatial roadmap for potential molecular interactions. Molecular docking simulations revealed that the complex exhibits high binding affinities toward MGLL (-8.3 kcal/mol) and COX-2 (PDB: 5IKQ) (-9.5 kcal/mol), forming stable interaction networks through conventional hydrogen bonds and pi-cationic contacts. These findings, corroborated by SwissTargetPrediction and pharmacophore mapping, suggest that the copper(II) complex is a rational candidate for further investigation in metabolic regulation and anti-inflammatory therapeutic strategies.
Three chalcone derivatives (2-MOP, 3-MOP and 4-MOP) containing 1,3-benzodioxole and anisole moieties were synthesized via the Claisen–Schmidt condensation reaction between mono-substituted methoxy acetophenones and piperonal in the presence of a base. The synthesized compounds were characterized using spectroscopic techniques (UV–Vis, FT-IR, FT-Raman, EI-MS, HR-ESI-MS and NMR) and the crystal structures of all three compounds were determined by single-crystal X-ray diffraction. Compounds 2-MOP and 4-MOP crystallize in the triclinic crystal system with space group P1 (2) and P1¯ (2), respectively, and Z = 2 per unit cell. Compound 3-MOP crystallizes in the orthorhombic crystal system with space group P212121 and Z = 4 per unit cell. The intermolecular interactions and crystal packing features of these chalcone derivatives were investigated by Hirshfeld surface analysis and two-dimensional fingerprint plots. UV–Visible absorption studies of chalcones (2-MOP, 3-MOP and 4-MOP) revealed broad-spectrum UV absorption in the 250–360 nm range, indicating their suitability as sunscreen agents. Density functional theory (DFT) calculations were carried out to identify the most promising candidate among the synthesized chalcones. The HOMO–LUMO energy gaps were calculated in the gas phase and in acetonitrile as the solvent, suggesting that compounds 3-MOP and 4-MOP are potential leads for the development of new sunscreen agents. All the synthesized compounds were docked into Matrix Metalloproteinase-1 (MMP-1) and Matrix Metalloproteinase-2 (MMP-2) to assess their capability as photoprotective agents. In silico toxicity assessment of the synthesized chalcones showed favorable safety profiles, with low cytotoxicity. The antioxidant potential of the synthesized compounds, along with Avobenzone, was evaluated by the DPPH free radical scavenging assay, with Quercetin as a reference. The results suggest that the tested compounds possess weak antioxidant activity compared to the standard antioxidant. The cytotoxic effects of avobenzone and chalcone derivatives were evaluated in L929 fibroblast cells using the MTT assay. Avobenzone displayed the lowest IC50 among the tested compounds, whereas 2-MOP demonstrated minimal cytotoxicity and greater biocompatibility. Furthermore, chalcone cream formulations (2-MOP, 3-MOP and 4-MOP) were prepared and physically evaluated over a period of three months by assessing parameters such as pH, viscosity, spreadability, centrifugation, freeze–thaw stability and emulsion stability.
A bis-imine Schiff base ligand (H2L) and its novel Fe(II), Ni(II), Cu(II), Pd(II), and Pt(II) complexes were synthesized and evaluated for their anticancer potential through combined experimental and computational approaches. Cytotoxic activities were assessed against human cancer cell lines together with normal L929 fibroblasts. Although the Fe(II) and Pt(II) complexes exhibited the strongest antiproliferative activities, the Pt(II) complex demonstrated the highest selectivity toward cancer cells, with selectivity index (SI) values of 5.74 for DLD-1 and 9.66 for A549, markedly exceeding that of cisplatin against A549 cells. To elucidate the structure–activity relationship (SAR) at the molecular level, density functional theory (DFT) calculations were performed at the B3LYP/6-311G(d,p) and B3LYP/LANL2DZ level of theory. The results demonstrated that metal coordination significantly modifies the electronic structure, reduces the HOMO-LUMO energy gap, and enhances electronic delocalization, particularly in the Pd(II) and Pt(II) complexes. Molecular electrostatic potential (MEP), total density of states (TDOS), and thermodynamic analyses further confirmed increased structural rigidity and electronic stabilization upon complex formation. Molecular docking studies targeting the kinase domain of 4UYA revealed favorable binding affinities for all complexes, with the Fe(II) complex displaying the lowest binding energy (–11.2 kcal/mol). Key interactions with residues such as LYS172, THR171, and MET182 were identified as major contributors to binding stabilization. To validate docking predictions, a 100 ns molecular dynamics simulation was performed for the FeL-4UYA complex. The stability of the system was confirmed by consistent RMSD, RMSF, radius of gyration, SASA, and hydrogen-bonding profiles, and by the preservation of secondary-structure elements throughout the trajectory. Overall, the integrated computational and biological findings underscore the significant potential of these metal-coordinated Schiff base frameworks for targeted cancer therapy.
Alpinia malaccensis (Burm.f.) Roscoe is a medicinally and economically important aromatic plant belonging to the Zingiberaceae plant family. This study aimed to isolate, characterize, and evaluate bioactive compounds from A. malaccensis fruits as potential plant-derived pesticidal agents. Bioactive compounds were isolated from the acetone extract of A. malaccensis fruits and structurally characterized using HRMS, FTIR, 1H NMR, 13C NMR, and DEPT-135 analyses. The isolated compounds were evaluated for their pesticidal potential, including nematicidal activity against Meloidogyne incognita, phytotoxic effects on Cichorium intybus and Raphanus raphanistrum subsp. sativus, and insect antifeedant activity against Spodoptera litura. In addition, structure activity relationship (SAR) analysis and molecular docking studies were conducted to understand the molecular basis of bioactivity. In-silico toxicity studies were also performed for the isolated compounds using ProTox 3.0 web server. Six compounds, α-humulene, malakavalactone, 2,4-dinitrophenylhydrazone-1,7-diphenyl-4,6-heptadien-3-one, sumadain A, a phenylbutenoid derivative, and calyxin H were isolated and identified based on spectroscopic analyses. Among these, malakavalactone exhibited the highest nematicidal, phytotoxic, and insect antifeedant activities. The SAR analysis revealed that pesticidal performance was strongly influenced by molecular weight, lipophilicity, polarity, and scaffold rigidity. Compounds possessing moderately high lipophilicity (LogP > 5), controlled polarity (TPSA ∼30–60 Å2), limited molecular flexibility, and balanced aromatic–aliphatic frameworks displayed enhanced bioactivities. Molecular docking further supported the experimental findings by demonstrating favorable ligand–protein interactions with nematode and insect target proteins. Furthermore, in silico toxicity predictions suggested an overall acceptable safety profile. Overall, the study highlights A. malaccensis as a promising source of structurally optimized, plant-derived pesticidal leads and provides mechanistic insight into pesticidal bioactivities.
The crystalline materials show drastic variations in the overall supramolecular structure and stability on halogen substitution at certain positions. These substituents modulate the electronic distribution and thereby influences intermolecular interactions. A series of three di-halogen substituted salicylidene Schiff base derivatives was synthesised and their formation was confirmed by spectroscopic techniques including 1H, 13C NMR, FTIR and UV-Vis spectroscopy. Single crystal X-ray diffraction studies confirmed the crystal structure and the influence of halogens on molecular conformation. Non-covalent interaction analysis using Hirshfeld surface and 3D energy frameworks revealed that the di-bromo derivative has the least lattice energy. Dispersive energy dominates in all the molecules when compared with electrostatic energy. Halogen-H interactions and halogen-π interactions play a major role in stabilizing the crystal lattice. The di-chloro derivative possesses the lowest void percentage due to the smaller atomic size of chlorine leading to a more compact arrangement. Quantum computational studies from DFT provided insights into the frontier molecular orbitals and chemical reactivity. The di-bromo derivative was found to possess the least kinetic stability. The synthesised compounds exhibited antibacterial activity against S. aureus, which is supported by molecular docking studies against S. aureus. The ADME profiling shed light on the drug-likeliness of the series. The structural activity analysis highlights the importance of structural modifications in altering the electronic distribution and governing the interactions in the crystal lattice.
