A cheminformatics and DFT exploration of a brominated sulfonamide with nonlinear optical response and preliminary in silico bioactivity assessment.

Structure-Property Relationships in Acylhydrazone-Based Molecules: Photophysics, Aggregation, and Metal-Binding Limitations.

This study investigates structure-property and structure-limitation relationships in a series of newly synthesised low-molecular-weight acylhydrazone derivatives obtained via ultrasonic-assisted condensation of heterocyclic aldehydes (pyrimidine, morpholine, and imidazole derivatives) with 4-methyl-1,2,3-thiadiazole-5-carboxylic acid hydrazide and 4-hydroxybenzhydrazide. The primary objective was to determine how structural variation within the heterocyclic and acyl fragments influences optical, electrochemical, thermal, and aggregation behaviour. Electrochemical studies revealed a single irreversible reduction process, mainly associated with the electron-withdrawing fragment, with LUMO orbital localization on the thiadiazole or hydrazone linkage, as supported by theoretical calculations. UV-Vis absorption maxima were largely solvent-independent across seven solvents of varying polarity. All compounds exhibited blue emission, except for the molecule containing the morpholine-thiadiazole derivative. However, the fluorescence quantum yields were low (Φ ≤ 4.1%), constituting a major photophysical limitation. Metal-complexation experiments showed weak optical responses to the tested metal cations, indicating limited binding affinity. Aggregation studies showed divergent behaviour depending on molecular structure, including aggregation-enhanced emission in the pyrimidine-thiadiazole derivative. Overall, the results demonstrate that although structural modification modulates electronic distribution and aggregation behaviour, the low emission efficiency and weak metal coordination significantly limit the potential of these materials for sensing or imaging applications.

Computational Exploration of the Structural, Electronic and Nonlinear Optical Properties of Substituted Piperidine Scaffold: A DFT and Molecular Docking Approach

An investigation into the structural, electronic and reactive properties of a substituted piperidine scaffold were conducted using density functional theory (DFT) at the B3LYP/6-31 G(d) level of theory. Molecular geometry optimization established a stable equilibrium structure. Frontier molecular orbital (FMO) analysis suggested a HOMO-LUMO energy gap of 5.6665 eV, consistent with high kinetic stability. Molecular electrostatic potential (MEP) mapping and Mulliken charge analysis identified the oxygen atoms as the principal nucleophilic centers, while the hydroxyl hydrogen bears a pronounced electrophilic character. Natural bond orbital (NBO) and non-covalent interaction (NCI) analyses quantified pronounced hyperconjugative stabilization and a complex network of hydrogen bonding interactions, particularly across the hydrazone linkage, which exhibited a Mayer bond order of 1.6852. The first-order hyper-polarizability was calculated as 1.044 × 10–30 esu, approximately 2.8-fold higher than that of urea, supporting the potential of the molecule for nonlinear optical (NLO) applications. Thermodynamic parameters exhibited strong temperature dependence, while STM and ALIE surface analyses identified the nitrogen-rich core as an electronically active region. Molecular docking against the 1BP1 protein yielded a binding energy of -6.4 kcal/mol, with hydrogen-bonding interactions involving VAL A:433 and PRO A:430. These computational findings support the relevance of the molecular scaffold for further investigation in medicinal chemistry and optoelectronic applications.

Synthesis, Structural Elucidation and DFT Studies of Novel Coumarin Derivative with Docking, ADMET Analysis and Antibacterial Activities

Elucidation of the spectral and structural characteristics of nitrofurantoin-4-hydroxybenzamide cocrystal.

Cocrystallization has emerged as an important strategy in supramolecular chemistry for tuning the physicochemical properties of active pharmaceutical ingredients (APIs). In this study, a cocrystal composed of nitrofurantoin (NF) and 4-hydroxybenzamide (4HBAM) is systematically investigated using combined experimental and computational approaches. Fourier-transform infrared (FT-IR) and Raman spectroscopy were employed to probe vibrational characteristics, while density functional theory (DFT) calculations were performed to optimize the molecular structure and evaluate interaction energies, thermodynamic parameters, and electronic properties. The calculated thermodynamic parameters yielded negative values of enthalpy (ΔH) and Gibbs free energy (ΔG), indicating that the formation of the NF-4HBAM (1,2) cocrystal is exothermic and thermodynamically favourable within the adopted DFT model, while the negative entropy change (ΔS) reflects the increased ordering accompanying cocrystal formation. The calculated interaction energy supports the stability of the hydrogen-bonded assembly. Spectroscopic results show pronounced red shifts in the vibrational frequencies of amide, phenolic OH, and carbonyl (CO) groups, suggesting the presence of strong intermolecular hydrogen bonds of the type NH···O and OH···OC. These interactions are further validated through atom-in-molecules (AIM) and natural bond orbital (NBO) analyses. Frontier molecular orbital analysis reveals a donor-acceptor electronic arrangement, with electron density localized primarily on 4HBAM (HOMO) and NF (LUMO), while global reactivity descriptors indicate increased polarizability and comparatively lower kinetic stability of the cocrystal relative to isolated components. Overall, the study provides a detailed molecular-level insight into the structural and spectroscopic behaviour of the NF-4HBAM system, highlighting its potential relevance in pharmaceutical applications.

Synthesis and multimodal characterization of flavonols: electrochemical, spectroscopic, and DFT approaches.

Five flavonols bearing electron-donating and electron-withdrawing substituents were synthesized and characterized by NMR spectroscopy, mass spectrometry, UV-Vis spectroscopy, and cyclic voltammetry. Density functional theory (DFT) and time-dependent DFT (TDDFT) calculations were performed to investigate their molecular geometries, frontier molecular orbitals, electronic structures, and excited-state properties. The optimized geometries revealed that flavonols containing substituents at both the C2' and C6' positions adopt non-planar conformations, whereas the remaining derivatives are essentially planar. Potential energy surface calculations showed that steric interactions between the 3-hydroxyl group and the ortho substituents stabilize the twisted conformations and reduce π-conjugation. The HOMOs were predominantly localized on rings B and C, while the LUMOs were distributed over rings A and C, indicating similar oxidation and reduction centres throughout the series. Electron-donating substituents raised the HOMO energies, resulting in lower oxidation potentials and red-shifted UV-Vis absorption bands. TDDFT calculations accurately reproduced the experimental absorption spectra and confirmed that the lowest-energy electronic excitation is dominated by the HOMO→LUMO transition. Strong correlations were observed between the experimental electrochemical energy gap and the DFT-calculated HOMO-LUMO energy gap (R2 = 0.92), while excellent agreement was obtained between the calculated and experimental absorption maxima (R2 = 0.98). The excellent agreement between experimental and computational parameters establishes quantitative structure-electronic property relationships for flavonols by integrating DFT, TDDFT, UV-Vis spectroscopy and electrochemistry, and provides a predictive basis for the rational design of flavonol-based functional materials and biologically active derivatives.

A novel pyridine-functionalized naphthoxazine: thermal stability, proton and metal ion-responsive optical sensing, and biological activity with DFT validation

Designing multifunctional polymers that combine thermal stability, selective optical response, and biological activity remains a key challenge in smart materials development. Herein, we report a novel pyridine-functionalized naphthoxazine monomer (Py-NZ) synthesized via a one-pot Mannich condensation and fully characterized by 1D/2D NMR, FTIR, and HRMS. DFT calculations confirmed the optimized geometry, showing excellent agreement with experimental data (RMSD = 0.018 Å; mean IR error = 0.43%), validating its extended π-conjugated structure. Thermogravimetric analysis of the cured Poly(Py-NZ) revealed outstanding thermal stability, with a char yield of 69% at 800 °C and a limiting oxygen index (LOI) of 45.1, indicating strong flame-retardant potential. UV–Vis and fluorescence spectroscopy demonstrated that metal coordination significantly modifies the optical behavior. Among the tested metal ions, Zn²⁺ induced a marked fluorescence enhancement due to its d¹⁰ configuration, which suppresses nonradiative decay and favors radiative emission. Py-NZ also exhibited strong acid-responsive fluorescence: high HCl concentrations quenched emission via protonation-induced nonradiative pathways, while lower acidity restored intensity, confirming its dual-responsive chemosensing capability for both metal ions and protons. Biological evaluation showed moderate antibacterial activity against Staphylococcus aureus and Escherichia coli , with the protonated form exhibiting enhanced activity against Gram-positive bacteria (MIC = 15.6 µg/mL). In DPPH antioxidant assays, all compounds displayed dose-dependent reductive activity comparable to ascorbic acid, with the Zn²⁺-coordinated complex showing the highest potency of nanomolarity radical scavenging affinities (IC₅₀ = 0.15 ± 0.01 vs. 0.041 ± 0.0062 for ascorbic acid). Overall, this work establishes a versatile platform for naphthoxazine-based multifunctional materials with potential applications in flame-retardant coatings, optical sensing, and biomedical fields.