Balanced Adsorption and Acidic-Condition Interfacial Reorganization of Anticancer Drugs on Doped ZnO Nanocarrier Interfaces

Here, we present a Sabatier-guided computational workflow to examine the interfacial adsorption and acidic-condition response of six anticancer drugs, namely 5-fluorouracil, capecitabine, cyclophosphamide, gemcitabine, methotrexate, and paclitaxel, on doped ZnO nanocarrier interfaces.

Mg-, Ca-, Na-, K-, and N-substituted ZnO models were evaluated using DFTB/COSMO/D3 calculations. Native nonprotonated adsorption was first used to construct drug-specific Sabatier windows and to select balanced-loading and weak-edge candidates. Selected monoprotonated (H1) and diprotonated (H2) microstates were then used as operational protonation challenges, motivated by mildly and more strongly acidic biological environments rather than interpreted as p<i>K</i>_a-weighted physical pH states, and were analyzed using geometry-based descriptors, including center-of-mass displacement, final cation–heteroatom contact distance, Zn···O/Zn···N contacts, and anchor switching.