Synthesis, Spectroscopic Characterization, DFT Studies and DNA Docking Analysis of an Ethylphenylazocalix[4]arene Derivative

An ethylphenylazocalix[4]arene derivative (25,26,27,28-tetrahydroxy-11,23-di(tert-butyl)-5,17-(4-ethylphenylazo)calix[4]arene) was synthesized and characterized using Fourier Transform Infrared (FT-IR) and Nuclear Magnetic Resonance (NMR) spectroscopy. To support the experimental findings and gain deeper insight into its structural properties, Density Functional Theory (DFT) calculations were carried out at the B3LYP/6-31G(d,p) level. The optimized geometry, vibrational frequencies and corresponding intensities were obtained, showing good agreement with the experimental data. The electronic properties of the compound were investigated using Frontier Molecular Orbitals (FMOs) and Total and Partial Density of States (TDOS and PDOS). The 1 H and [Formula: see text]C NMR chemical shifts were predicted using the Gauge-Independent Atomic Orbital (GIAO) method and found to be consistent with the experimental results. The calculated first-order hyperpolarizability ([Formula: see text], along with related parameters ([Formula: see text], [Formula: see text], and [Formula: see text], indicates a notable Nonlinear Optical (NLO) response. Molecular Electrostatic Potential (MEP) analysis revealed the charge distribution and potential reactive sites of the molecule, while Hirshfeld Surface Analysis (HSA) indicated that crystal packing is primarily stabilized by hydrogen bonding and [Formula: see text] interactions. Molecular docking results suggest that the derivative may interact with B-DNA through a groove-binding mode. Additionally, Molecular Dynamics (MDs) simulations (100 ns, GROMACS) were performed to further assess the stability of the docked complexes, and the results indicate that the interactions are generally stable. These findings offer a computational insight into the structural, electronic and interaction properties of the studied calix[4]arene derivative, although further experimental validation is required to confirm their biological relevance.