<p>Pharmaceuticals as emerging contaminants (EC) in water are one of the major challenges for the future. In this context, the reactivity of selective ECs such as ibuprofen, paracetamol, aspirin, metronidazole, and metoprolol, and their interaction with 4-nitrotoluene (4-NT) are discussed in the light of density functional theory (DFT). The analysis highlights the favorable formation of 4-NT–EC complexes with interaction energies within the range of –13.18 to–6.28 kcalmol⁻¹. The complex formation is exothermic and occurs via non-covalent interactions. Effective interaction leads to changes in the energy of molecular orbitals (MOs) and subsequent alterations in global reactivity descriptors. QTAIM and NCI analyses have also suggested the presence of van der Waals forces between 4-NT and ECs. The findings of this work provide a theoretical basis for future studies on wastewater treatment and the adsorption of ECs onto nitro-substituted materials.</p> Graphical Abstract <p></p>