Das_2026_ACS.Omega_11_52994

Organophosphorus nerve agents exert their toxicity by irreversibly inhibiting acetylcholinesterase, disrupting neurotransmission in both the central and peripheral nervous systems. Consequently, rapid and reliable recognition of these agents is crucial for timely detection and mitigation. Herein, we investigate size-selective host-guest interactions between a supramolecular pinwheel and a modeled tetracene-based host with G-series nerve agents as guests, using density functional theory (DFT) at the M06-2X-D3/6-31+G-(d) level. The computational results demonstrated that the G-series nerve agent Tabun (GA) exhibits stronger affinity and higher selectivity for encapsulation with the supramolecular pinwheel host. Similarly, Soman (GD) and Cyclosarin (GF) are effectively encapsulated within the electron-rich tetracene-based host cavity, with higher binding energies than those of the congener nerve agents. All host-guest complexes are thermodynamically favorable. Stabilization arises from multiple noncovalent interactions, including C-H...F, C-H...O hydrogen bonding, C-H...Pi interactions, and van der Waals forces, along with structural complementarity between host and guest. Noncovalent interactions are characterized using molecular electrostatic potential (MESP) surface topography and atoms-in-molecules (AIM) analysis, in conjunction with the reduced density gradient (RDG) method for noncovalent interaction visualization. Energy decomposition analysis further elucidates the nature and contributions of interactions governing the stability of these encapsulated complexes.