6 research outputs found
Ubiquitous Assembly of Amphiphilic Baskets into Unilamellar Vesicles and Their Recognition Characteristics
An
amphiphilic basket of type <b>1</b> (339 Å<sup>3</sup>)
has been found to assemble into unilamellar vesicles in water.
The assembled host encapsulates organophosphonates (OPs) (119–185
A<sup>3</sup>) with a particularly high affinity (<i>K</i><sub>a</sub> ∼ 10<sup>5</sup> M<sup>–1</sup>) toward
dimethyl phenylphosphonate (185 Å<sup>3</sup>) whose size and
shape resemble that of soman (186 Å<sup>3</sup>). 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 Å<sup>3</sup>) for trapping variously
sized and shaped organophosphonates (OPs) <b>2</b>–<b>12</b> (137–244 Å<sup>3</sup>) 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 A<sup>3</sup>). Importantly, baskets assemble into a vesicular
nanomaterial (<i>D</i><sub>H</sub> ≈ 350 nm) that
in the presence of neutral OP compounds undergoes a phase transition
to give nanoparticles (<i>D</i><sub>H</sub> ≈ 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><sub>H</sub> ≈
750 nm). The interconversion of the different nanostructures is reversible
and, moreover, a function of the organophosphonate present in solution.
On the basis of <sup>1</sup>H 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><sub>3</sub>-symmetric hydrophobic
cage (477 Å<sup>3</sup>)
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 Å<sup>3</sup>) in its cavity (<i>K</i><sub>app</sub> = (1.97 ± 0.02) × 10<sup>3</sup> M<sup>–1</sup>). The entrapment of the organophosphonate,
akin to soman in size (186 Å<sup>3</sup>), 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><sub>3</sub>-symmetric hydrophobic
cage (477 Å<sup>3</sup>)
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 Å<sup>3</sup>) in its cavity (<i>K</i><sub>app</sub> = (1.97 ± 0.02) × 10<sup>3</sup> M<sup>–1</sup>). The entrapment of the organophosphonate,
akin to soman in size (186 Å<sup>3</sup>), 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