Design and Prediction Physicochemical Properties of Piperazinium and Imidazolidinium Based Ionic Liquids: A DFT and Docking Studies

Abstract

This study investigates the chemical stability, ionic interactions, and drug efficacy of piperazinium and imidazolidinium cations. Analogous to carmustine [CA1]+, [CA2]+, gemcitabine [GE1]+, [GE2]+, and caulibugulone [CU1]+—paired with nitrate [NO3]−, triflate [CF3SO3]−, and mesylate [CH3SO3]− ions across gas and solvent phases (benzene and water). Molecular orbital analysis revealed that the [CU1]+[NO3]− ionic pair exhibits the smallest Egap in all phases, suggesting high reactivity and increased solubility. The interaction energies Eint of [CU1]+[NO3]− were determined to be −602.41 kcal/mol in the gas phase, −570.65 kcal/mol in benzene, and −514.17 kcal/mol in water, reflecting robust interionic forces. Toxicity evaluation based on the TOX21 pathway indicates that these IL pairs are nontoxic and possess excellent potential as therapeutic candidates. In silico docking studies against the protein (PDB ID: 1B38) demonstrated that [CA1]+, [CA2]+, [CU1]+, [GE1]+, and [GE2]+ exhibit binding energies of −5.74, −5.52, −5.81, −5.65, and −5.60 kcal/mol, respectively. Notably, the standard drugs carmustine and gemcitabine showed slightly weaker binding affinities than [CA2]+. MD simulations reinforced these findings, with RMSD analysis confirming the structural stability of the ligand-protein complexes. In conclusion, the newly identified drug-based ILs exhibit superior binding affinities and favorable bioinformatics profiles, making them potential candidates for drug development.