Colorectal cancer (CRC) remains a major global health challenge, with chronic inflammation and disruption of epithelial polarity identified as key drivers of tumor progression. Polarity complexes such as Scribble–Mutated in Colorectal Cancer (MCC) are central to maintaining epithelial homeostasis, and their dysregulation has been linked to oncogenic transformation. Drug repurposing offers a promising strategy to accelerate therapeutic discovery by identifying new applications for clinically approved agents. In this study, we investigated abrocitinib (ABR), a selective JAK1 inhibitor, as a candidate for repurposing in CRC. Density functional theory (DFT) calculations at the PBE0-D3/6-31G(d) level were used to examine its electronic properties, including geometry optimization, natural bond orbital (NBO) analysis, molecular electrostatic potential (MESP) mapping, and Fukui function analysis. ABR exhibited a moderate HOMO–LUMO gap (1.827 eV) and an electrophilicity index of 3.492 eV, consistent with favorable reactivity and stability. Molecular docking with the Scribble PDZ1 domain (PDB ID: 6MTV) predicted a strong binding affinity (MolDock score − 78.66 kcal/mol; rerank score − 55.69 kcal/mol), supported by electrostatic and hydrophobic interactions. Importantly, comparative docking with fluorouracil and capecitabine demonstrated that ABR achieved more favorable binding energies and greater interaction stability than these reference CRC drugs, highlighting its superior potential to disrupt Scribble–MCC interactions. Monte Carlo simulations and normal mode analysis further confirmed the dynamic stability of the ABR–PDZ1 complex. Collectively, these findings provide preliminary evidence that abrocitinib may act as a promising modulator of polarity-regulating protein–protein interactions in CRC. While experimental validation remains necessary, this study establishes a computational framework that supports further biochemical and cellular investigations into abrocitinib’s potential as a repurposed therapeutic candidate.

Cyanogenic gases, such as hydrogen cyanide and cyanogen, are highly toxic and pose serious risks to both human health and the environment. Effective adsorption strategies are essential to mitigate these hazards. In this study, the adsorption potential of a silver-decorated and yttrium-doped silicon nanocluster (Ag@Si₅₉Y) toward cyanogenic gases—BrCN, ClCN, and FCN—was investigated using density functional theory (DFT) at the ωB97XD/GenECP/LanL2DZ/Def2SVP level of theory. Adsorption was explored in two orientations for each gas molecule. The computed adsorption energies indicated favorable interaction, particularly for BrCN, with values of −30.121, −17.571, −17.571, −16.943, −16.316, and −16.316 kcal mol⁻¹ for BrCN–Br–, BrCN–N–, ClCN–Cl–, ClCN–N–, FCN–F–, and FCN–N–Ag@Si₅₉Y complexes, respectively. BrCN showed the strongest affinity, suggesting preferential adsorption on the Ag@Si₅₉Y surface. Noncovalent interaction (NCI) analysis and recovery time calculations confirmed the presence of strong chemisorptive interactions, especially for BrCN, characterized by significant charge transfer and bonding stability. The frontier molecular orbital (FMO) analysis revealed a notable reduction in the energy gap upon gas adsorption, highlighting the enhanced reactivity of the surface. High dipole moment values across all adsorbed complexes indicate substantial charge separation, which is advantageous for sensor-based applications. Furthermore, the Electron Localization Function (ELF) analysis provided visual insight into the nature of bonding interactions. ELF maps exhibited moderate to high localization around the adsorption regions, particularly in BrCN–Br–Ag@Si₅₉Y and FCN–N–Ag@Si₅₉Y, suggesting mixed covalent and noncovalent bonding characteristics. These observations corroborate findings from QTAIM and NBO analyses, validating the interaction types and reinforcing the reliability of the proposed adsorption mechanisms. Thus, Ag@Si₅₉Y demonstrates strong and selective adsorption properties toward cyanogenic gases, making it a promising candidate for use in gas sensing and environmental detoxification technologies.