title: The prospect of selective recognition of nerve agents with modular basket-like hosts. A structure-activity study of the entrapment of a series of organophosphonates in aqueous media.
abstract: We designed, prepared, and characterized three cup-shaped cavitands 1-3 for trapping organophosphonates (O═PR(OR')2, 118-197 Å(3)) whose shape and size correspond to G-type chemical warfare agents (132-186 Å(3)). With the assistance of computational (molecular dynamics) and experimental ((1)H NMR spectroscopy) methods, we found that host [1-H3](3+) orients its protonated histamine residues at the rim outside the cavity, in bulk water. In this unfolded form, the cavitand traps a series of organophosphonates 5-13 (K(app) = 87 ± 1 to 321 ± 6 M(-1) at 298.0 K), thereby placing the P-CH3 functional group in the inner space of the host. A comparison of experimental and computed (1)H NMR chemical shifts of both hosts and guests allowed us to derive structure-activity relationships and deduce that, upon the complexation, the more sizable P-OR functional groups in guests drive organophosphonates to the northern portion of the basket [1-H3](3+). This, in turn, causes a displacement of the guest's P-CH3 group and a contraction of the cup-shaped scaffold. The proposed induced-fit model of the recognition is important for turning these modular hosts into useful receptors capable of a selective detection/degradation of organophosphorus nerve agents.
authors: Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio, United States.
authors: Yian
authors: Y
authors: Ruan
authors: Hashem A
authors: HA
authors: Taha
authors: Ryan J
authors: RJ
authors: Yoder
authors: Veselin
authors: V
authors: Maslak
authors: Christopher M
authors: CM
authors: Hadad
authors: Jovica D
authors: JD
authors: Badjić
mesh_terms: D002619:Chemical Warfare Agents / Q000737:chemistry*; D004988:Ethers, Cyclic / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D062105:Molecular Docking Simulation; D063065:Organophosphonates / Q000737:chemistry*; D012118:Resorcinols / Q000737:chemistry; D012995:Solubility; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry
chemical_list: D002619:Chemical Warfare Agents; D004988:Ethers, Cyclic; D063065:Organophosphonates; D012118:Resorcinols; C442939:cavitand; D014867:Water