Hemoglobin (H) plays a crucial role in drug transport because it binds various biomolecules and facilitates their circulation in the bloodstream. This study investigates the interactions of hemoglobin with four drugs: aspirin, isoniazid, 5-fluorouracil, and flucytosine using Density Functional Theory (DFT) and Time-Dependent DFT (TD-DFT) methods at the GD3- B3LYP/6-31G(d,p) levels of theory. The optimized drug-hemoglobin complexes reveal the strongest interactions for isoniazid (Eads − 61.12 kcal/mol) and flucytosine (Eads = − 53.52 kcal/mol), as confirmed by adsorption energy calculations. Solvent effects demonstrate that ethanol enhances these interactions, further stabilizing the complexes. UV–visible and density of states (DOS) and projected density of states (PDOS) analyses indicate significant structural and electronic modifications in hemoglobin upon drug binding. Non-covalent interactions, including van der Waals forces, hydrogen bonding, and electrostatic interactions, govern the adsorption process, ensuring stable drug transport. The findings highlight hemoglobin’s potential as an efficient drug carrier, particularly for isoniazid and flucytosine, and provide valuable insights for designing advanced hemoglobin-based drug delivery systems. This study enhances our understanding of hemoglobin’s transport mechanisms, offering a foundation for improving targeted and controlled drug release strategies in therapeutic applications.
