Synthesis, Spectral Characterization, and Multi‐Scale Computational Insights Into Imidazo[1,2‐a]pyridine–Thiadiazole‐Based Schiff Bases

ABSTRACT A new series of conjugated heteroaromatic compounds 2‐(4‐bromophenyl) imidazo[1,2‐a]pyridine (A1), Mannich base derivative (A2), thiadiazole‐fused imidazo[1,2‐a]pyridine (A3), and Schiff base derivatives (A4–A7) bearing ─NO 2 , ─Cl, ─OCH 3 , and ─OH groups, was designed and analyzed using DFT and MD simulations. All geometries were optimized at B3LYP/6‐311G (d, p) and confirmed as minima. QTAIM/NCI–RDG analyses showed strong C─N (amide) and N─S (thiadiazole) covalency ( ρ ≈ 0.21 a.u. and ∇ 2 ρ ≈ −4.4×10 7 a.u.) with weak π–π and H‐bond stabilization. MD simulations (NVE, 310 K, 100 ps) indicated stable total energies ( σ < 0.5 kcal·mol − 1 ) and increasing values from A1 (≈202) to A7 (≈425 kcal·mol − 1 ) due to extended conjugation. RDF peaks (1.0–1.6 Å) confirmed C─N, N─S, and C═O bonding, while MSD gave diffusion coefficients from (1–8)×10 − 3 Å 2 ·ps − 1 (A1–A3) to 1.2×10 − 1 −4.4×10 − 2 Å 2 ·ps − 1 (A4–A7), revealing a mobility trend A1 < A2 < A3 < A4< A5 < A6 < A7. The presence of electron‐rich nitrogen and sulfur atoms provides active sites for adsorption, while HOMO–LUMO characteristics support charge‐transfer interactions relevant to potential applications.