A computational study on acetaminophen drug complexed with Mn+, Fe2+, Co+, Ni2+, and Cu+ ions: structural analysis, electronic properties, and solvent effects

In the present research, the cation–π interactions in acetaminophen-M complexes (M = Mn+, Fe2+, Co+, Ni2+, and Cu+) are investigated using density functional theory (DFT/ωB97XD) in the gas phase and solution. The results show that the absolute values of energy are reduced in going from the gas phase to the solution. Based on the obtained data, the complexes in water are the most stable. The natural bond orbital (NBO) and the atoms in molecules (AIM) analyses are also applied to achieve more details about the nature of interactions. These results are useful for understanding the role of the drug-receptor interactions in the complexes. According to AIM outcomes, the cation–π interactions are the closed-shell and may indicate the partially covalent nature in the complexes. A comprehensive analysis is also performed on the conceptual DFT parameters of the complexes to evaluate their electronic properties. Our findings show increasing the stability and decreasing the reactivity of the complexes in the solution phase with respect to the gas phase. These interactions are ubiquitous in biological systems, and their importance in theoretical models led us to study such important interactions. The results of this study may be useful for the design and synthesis of a variety of supramolecular complexes with the desired properties.