Electronic reactivity and drug binding in doped cycloparaphenylenes: toward multifunctional platforms for biosensing and targeted drug delivery.

Cycloparaphenylenes (CPP) and their heteroatom-doped derivatives are emerging as interesting nanocarriers due to their adjustable electronic structures and π-conjugated frameworks. This study used density functional theory (DFT) to examine the structural, electrical, and adsorption characteristics of virgin CPP, nitrogen-doped CPP (N-CPP), and oxygen-doped CPP (O-CPP) in relation to two anticancer agents, hydroxyurea (HU) and thioguanine (TG). Geometry optimization verified the inherent stability of all carriers, whereas doping induced localized distortions that increased reactivity. Electronic tests indicated a consistent decrease in the energy gap after medication adsorption. HU functioned as a weak electron donor, resulting in little gap narrowing, whereas TG operated as a robust electron acceptor, causing substantial band-gap quenching-particularly in TG@O-CPP, where the gap practically disappeared, resulting in metallic-like behavior. Adsorption energies (-0.10 to -1.13 eV) and recovery periods revealed divergent kinetics: HU complexes desorbed almost quickly, while TG demonstrated more robust binding and extended residence lengths, especially on O-CPP. Charge-transfer research validated the contrasting donor-acceptor functions of HU and TG, supported by global reactivity indices indicating heightened electrophilicity and reduced hardness upon TG adsorption. The findings identify TG@O-CPP as the most promising system, with improved adsorption strength, substantial charge transfer, notable band-gap reduction, and adjustable electrical responsiveness. These results provide significant insights for the systematic design of CPP-based nanostructures in biosensing applications that need rapid reaction and in drug-delivery systems that require controlled release.