Akademik Veri Yönetim Sistemi
Journal of Molecular Structure, cilt.1358, 2026 (SCI-Expanded, Scopus)
N-(4-(3-methyl-3mesitylcyclobutyl)-1H-imidazol-2-yl)acetamide (MMCIA), a cyclobutane–imidazole derivative, was synthesized and investigated through an integrated experimental and theoretical approach to elucidate its structural, electronic, and pharmacological features. Single-crystal X-ray diffraction analysis revealed that MMCIA crystallizes in the triclinic P1¯ space group, with the crystal packing stabilized by a cooperative network of N–H···O and N–H···N hydrogen bonds, supported by C–H···π interactions. Hirshfeld surface analysis quantified the dominant intermolecular contacts, indicating that H···H (69.1%) and C···H/H···C (11.9%) interactions play a major role in lattice stabilization. Density Functional Theory (DFT) calculations at the B3LYP/6–311G(d,p) level further supported the molecular stability, revealing a HOMO–LUMO energy gap of 3.72 eV, a chemical hardness of 1.86 eV, and a relatively high electrophilicity index of 12.2 eV, indicating moderate kinetic stability together with a pronounced electrophilic character. Molecular electrostatic potential mapping and reduced density gradient analysis provided complementary insight into the distribution of electrophilic/nucleophilic regions and the nature of weak non-covalent interactions governing molecular stability. Molecular docking studies against tubulin A predicted a favorable binding affinity of −7.87 kcal/mol, corresponding to an estimated inhibition constant (Ki) of approximately 1.7 µM., indicating potential inhibitory activity. In silico ADME and drug-likeness evaluations, including the BOILED-Egg model, suggested high gastrointestinal absorption, blood–brain barrier permeability, and full compliance with Lipinski's rule of five.