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

We designed, prepared, and characterized three cup-shaped cavitands <b>1</b>–<b>3</b> for trapping organophosphonates (OPR­(OR′)₂, 118–197 ų) whose shape and size correspond to G-type chemical warfare agents (132–186 ų). With the assistance of computational (molecular dynamics) and experimental (¹H NMR spectroscopy) methods, we found that host [<b>1</b>–<b>H</b>₃]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 <b>5</b>–<b>13</b> (<i>K</i>_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 ¹H 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 [<b>1</b>–<b>H</b>₃]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

Method for the Preparation of Derivatives of Heptiptycene: Toward Dual-Cavity Baskets

We have developed a novel synthetic method that enables the preparation of functional derivatives of heptiptycene, i.e., cavitands with two juxtaposed cavities. The homocoupling of bicyclic dibromoalkenes is promoted by Pd­(OAc)₂ (10%) in dioxane (100 °C) to give cyclotrimers in 27–77% yield under optimized reaction conditions (Ph₃P, K₂CO₃, <i>n</i>-Bu₄NBr, N₂, 4 Å MS). These dual-cavity baskets show a strong π → π* absorption at 241 nm (ε = 939 000 M^–1 cm^–1), along with a subsequent fluorescence emission at 305 nm