Unlocking methotrexate-chitosan interactions through classical and statistical physics adsorption modeling

• First study integrating classical and statistical physics for MTX adsorption; • Physisorption dominates, governed by hydrogen bonding interactions; • High adsorption capacity achieved (118.22 mg g −1 ) by chitosan. The presence of methotrexate (MTX), a persistent cytotoxic pharmaceutical (concentrations ranging from 1.6 to 4756 ng L −1 ), in aquatic environments poses significant environmental and public health risks, demanding effective remediation strategies. This study provides the first detailed description of MTX adsorption onto chitosan by combining classical isotherm analysis with a statistical physics-based modeling approach. In this context, MTX removal from aqueous solutions was investigated using chitosan, a biodegradable biopolymer widely applied as an adsorbent. The equilibrium data were interpreted using both conventional and advanced statistical physics models, thereby enabling a deeper understanding of the adsorption mechanism. To our knowledge, this is the first work to report these two complementary models simultaneously for describing MTX adsorption on chitosan. The Sips model showed the best fit among the classical models, suggesting multilayer adsorption on heterogeneous sites. The adsorption capacity estimated by the Sips model was 118.22 mg g −1 . An exothermic and spontaneous process occurred. The magnitude of ∆H° values suggested a physisorption mechanism. At the same time, statistical physics modeling revealed that the double-layer model with a single energy site best described the system. This model indicated that n increased with rising temperature ( n = 1.25–7.10). Additionally, the n parameter indicates that MTX has a non-parallel surface arrangement. Adsorption energy ranging from 13.48 to 16.44 kJ mol −1 also corroborated with classical thermodynamic parameters and FTIR results, indicating the predominance of physical interactions, such as the hydrogen bonds.