Antimicrobial activity of bis(4-carboxyanilinium) selenate and its interaction with synthetic liposomes: A...

Bis(4-carboxyanilinium) selenate (B4-CASeO₄) was investigated as a membrane-active antimicrobial agent using microbiological, biophysical, and computational approaches. The compound exhibits broad-spectrum antimicrobial activity, with minimum inhibitory concentrations (MICs) of 2.63 mg mL⁻¹ against Escherichia coli, Bacillus subtilis, and Staphylococcus carnosus, and 1.31 mg mL⁻¹ against Saccharomyces cerevisiae. The minimum bactericidal concentration (MBC) values were comparable to the corresponding MIC values, consistent with a bactericidal mode of action. Biophysical studies using DPPC and DPPE model membranes reveal concentration- and time-dependent membrane perturbation, characterized by increased phase transition temperature, altered transition enthalpy, vesicle size growth, and a significant increase in zeta potential, indicating enhanced bilayer ordering and interfacial reorganization. Fluorescence measurements further indicate increased exposure of hydrophobic regions upon interaction with B4-CASeO₄. Molecular dynamics simulations show that 4-carboxyanilinium cations preferentially localize at the lipid-water interface, inducing bilayer ordering without deep penetration, while selenate ions remain largely solvated. Additional simulations performed with the physiologically relevant anionic form of 4-aminobenzoic acid (4-ABA) showed predominantly interfacial localization with weak transient membrane interactions. Docking studies suggest favorable binding of the cationic component to key microbial enzymes, supporting a dual mechanism involving membrane modulation and enzyme inhibition. Comparative analysis with 4-aminobenzoic acid confirms the enhanced efficacy of B4-CASeO₄. These findings establish B4-CASeO₄ as a promising membrane-active antimicrobial agent.