Recognition Characteristics of an Adaptive Vesicular Assembly of Amphiphilic Baskets for Selective Detection and Mitigation of Toxic Nerve Agents

We used isothermal titration calorimetry to investigate the affinity of basket <b>1</b> (470 ų) for trapping variously sized and shaped organophosphonates (OPs) <b>2</b>–<b>12</b> (137–244 ų) in water at 298.0 K. The encapsulation is, in each case, driven by favorable entropy (<i>T</i>Δ<i>S</i>° = 2.9 kcal/mol), while the enthalpic component stays small and in some cases endothermic (Δ<i>H</i>° ≥ −1 kcal/mol). Presumably, a desolvation of basket <b>1</b> and OP guests permits the inclusion complexation at room temperature via a “classical” hydrophobic effect. The amphiphilic basket <b>1</b> shows a greater affinity (Δ<i>G</i>° ≈ −5 to −6 kcal/mol), both experimentally and computationally, for encapsulating larger organophosphonates whose size and shape correspond to VX-type agents (289 A³). Importantly, baskets assemble into a vesicular nanomaterial (<i>D</i>_H ≈ 350 nm) that in the presence of neutral OP compounds undergoes a phase transition to give nanoparticles (<i>D</i>_H ≈ 250 nm). Upon the addition of an anionic guest to basket <b>1</b>, however, there was no formation of nanoparticles and the vesicles grew into larger vesicles (<i>D</i>_H ≈ 750 nm). The interconversion of the different nanostructures is reversible and, moreover, a function of the organophosphonate present in solution. On the basis of ¹H NMR spectroscopic data, we deduced that neutral guests insert deep into the basket’s cavity to change its shape and thereby promote the conversion of vesicles into nanoparticles. On the contrary, the anionic guests reside at the northern portion of the host to slightly affect its shape and geometric properties, thereby resulting in the vesicles merely transforming into larger vesicles

Ubiquitous Assembly of Amphiphilic Baskets into Unilamellar Vesicles and Their Recognition Characteristics

An amphiphilic basket of type <b>1</b> (339 ų) has been found to assemble into unilamellar vesicles in water. The assembled host encapsulates organophosphonates (OPs) (119–185 A³) with a particularly high affinity (<i>K</i>_a ∼ 10⁵ M^–1) toward dimethyl phenylphosphonate (185 ų) whose size and shape resemble that of soman (186 ų). Importantly, the entrapment of OPs prompts a phase transformation of vesicular <b>1</b> into nanoparticles or larger vesicles as a function of the shape of the host–guest complex

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

Assembly of Amphiphilic Baskets into Stimuli-Responsive Vesicles. Developing a Strategy for the Detection of Organophosphorus Chemical Nerve Agents

We designed basket <b>1</b> to comprise a <i>C</i>₃-symmetric hydrophobic cage (477 ų) at its southern edge and three polar ammonium caps at the northern edge. This amphiphilic molecule was observed to assemble into large unilamellar vesicles (350 nm, TEM) in water and thereby entrap dimethyl phenylphosphonate (184 ų) in its cavity (<i>K</i>_app = (1.97 ± 0.02) × 10³ M^–1). The entrapment of the organophosphonate, akin to soman in size (186 ų), triggers the transformation of the vesicular material into nanoparticles (100 nm, TEM). Stimuli-responsive vesicles, containing baskets of type <b>1</b> in their bilayer membrane, are unique assemblies and important for obtaining novel sensing devices

Assembly of Amphiphilic Baskets into Stimuli-Responsive Vesicles. Developing a Strategy for the Detection of Organophosphorus Chemical Nerve Agents

We designed basket <b>1</b> to comprise a <i>C</i>₃-symmetric hydrophobic cage (477 ų) at its southern edge and three polar ammonium caps at the northern edge. This amphiphilic molecule was observed to assemble into large unilamellar vesicles (350 nm, TEM) in water and thereby entrap dimethyl phenylphosphonate (184 ų) in its cavity (<i>K</i>_app = (1.97 ± 0.02) × 10³ M^–1). The entrapment of the organophosphonate, akin to soman in size (186 ų), triggers the transformation of the vesicular material into nanoparticles (100 nm, TEM). Stimuli-responsive vesicles, containing baskets of type <b>1</b> in their bilayer membrane, are unique assemblies and important for obtaining novel sensing devices

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