DFT-based computational insights and biological evaluation of N , N -dimethylamino pyridinium halide Lewis Base adducts

This study investigates the geometric and electronic properties of N,N-dimethylamino pyridinium halide Lewis base adducts using density functional theory (DFT) and assesses their antibacterial efficacy. DFT calculations were conducted on 11 pyridinium salts, to analyze geometry, electronic structure and chemical reactivity. Key quantum chemical parameters including electron affinity (A), ionization potential (I), electron negativity (χ), HOMO-LUMO energy gap ΔE, electrophilicity index (ω), dipole moment (μ), hardness (η) and softness (S) were derived to predict potential sites for nucleophilic and electrophilic attacks. The antibacterial activity of these compounds was evaluated in vitro against four Gram negative and three Gram positive bacteria using the broth dilution method. Compounds A (4-(dimethylamino)-1-tosyl pyridinium chloride) and E (1-bromo-4-(dimethylamino) pyridinium bromide) demonstrated complete inhibition of all seven tested bacterial strains at a concentration of 20 ppm. Compound 2 (4-(dimethylamino)-1-(phenylsulfonyl) pyridinium chloride) exhibited moderate activity against Salmonella typhimurium (Gram-negative) and Bacillus subtilis (Gram-positive). Compound B (1-benzyl-4-(dimethylamino) pyridinium chloride) inhibited two Gram-negative bacteria (Shigella boydi, S.typhimurium) and two Gram-positive (Streptococcus sp., Staphylococcal sp.) bacteria. The findings provide valuable insights into the relationship between the electronic properties of N,N-dimethylamino pyridinium halide adducts and their antibacterial activity, suggesting that specific structural features contribute to enhanced antibacterial efficacy.