Computational Investigation of 4‑Nitrophenol Inclusion Complexes with α‑, β‑, and γ‑Cyclodextrins

The increasing presence of emerging contaminants, such as 4-nitrophenol (4-NP), in aquatic environments poses environmental and public health risks, driving interest in innovative systems capable of selectively removing them. Despite the well-established potential of cyclodextrins (CDs) as molecular hosts for the removal of organic micropollutants, owing to their ability to reduce contaminant mobility and availability while promoting capture, isolation, and preconcentration, as well as their biodegradability and low toxicity, and increasing their chemical versatility, a comprehensive theoretical comparison of their interactions with 4-NP is still lacking. The present study explores the formation and stability of inclusion complexes between 4-NP and three types of cyclodextrins (α-CD, β-CD, and γ-CD) using a combination of docking, molecular dynamics, and ab initio density functional theory (DFT) calculations. The results show that α-CD exhibits the strongest and most stable interaction with 4-NP, followed by β-CD. At the same time, γ-CD exhibits lower retention, consistent with a cavity-guest size mismatch and structural complementarity on molecular interactions. These findings not only provide molecular-level insights into host-guest interactions but also reinforce the potential application of cyclodextrins as effective, biodegradable, and reusable materials, offering theoretical support for their use in environmental remediation strategies and their potential for reuse, making them a sustainable and cost-effective solution.