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

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

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

Study of <i>para</i>-Quinone Methide Precursors toward the Realkylation of Aged Acetylcholinesterase

Acetylcholinesterase (AChE) is an essential enzyme that can be targeted by organophosphorus (OP) compounds, including nerve agents. Following exposure to OPs, AChE becomes phosphylated (inhibited) and undergoes a subsequent aging process where the OP–AChE adduct is dealkylated. The aged AChE is unable to hydrolyze acetylcholine, resulting in accumulation of the neurotransmitter in the central nervous system (CNS) and elsewhere. Current therapeutics are only capable of reactivating inhibited AChE. There are no known therapeutic agents to reverse the aging process or treat aged AChE. Quinone methides (QMs) have been shown to alkylate phosphates under physiological conditions. In this study, a small library of novel quinone methide precursors (QMPs) has been synthesized and examined as potential alkylating agents against model nucleophiles, including a model phosphonate. Computational studies have been performed to evaluate the affinity of QMPs for the aged AChE active site, and preliminary testing with electric eel AChE has been performed

Study of <i>para</i>-Quinone Methide Precursors toward the Realkylation of Aged Acetylcholinesterase

Acetylcholinesterase (AChE) is an essential enzyme that can be targeted by organophosphorus (OP) compounds, including nerve agents. Following exposure to OPs, AChE becomes phosphylated (inhibited) and undergoes a subsequent aging process where the OP–AChE adduct is dealkylated. The aged AChE is unable to hydrolyze acetylcholine, resulting in accumulation of the neurotransmitter in the central nervous system (CNS) and elsewhere. Current therapeutics are only capable of reactivating inhibited AChE. There are no known therapeutic agents to reverse the aging process or treat aged AChE. Quinone methides (QMs) have been shown to alkylate phosphates under physiological conditions. In this study, a small library of novel quinone methide precursors (QMPs) has been synthesized and examined as potential alkylating agents against model nucleophiles, including a model phosphonate. Computational studies have been performed to evaluate the affinity of QMPs for the aged AChE active site, and preliminary testing with electric eel AChE has been performed