Gating the Trafficking of Molecules across Vesicular Membrane Composed of Dual-Cavity Baskets

Gating the Trafficking of Molecules across Vesicular Membrane Composed of Dual-Cavity Basket

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

Russian Nesting Doll Complexes of Molecular Baskets and Zinc Containing TPA Ligands

In this study, we examined the structural and electronic complementarities of convex <b>1</b>–Zn­(II), comprising functionalized tris­(2-pyridylmethyl)­amine (TPA) ligand, and concave baskets <b>2</b> and <b>3</b>, having glycine and (<i>S</i>)-alanine amino acids at the rim. With the assistance of ¹H NMR spectroscopy and mass spectrometry, we found that basket <b>2</b> would entrap <b>1</b>–Zn­(II) in water to give equimolar <b>1</b>–Zn⊂<b>2</b>_in complex (<i>K</i> = (2.0 ± 0.2) × 10³ M^–1) resembling Russian nesting dolls. Moreover, <i>C</i>₃ symmetric and enantiopure basket <b>3</b>, containing (<i>S</i>)-alanine groups at the rim, was found to transfer its static chirality to entrapped <b>1</b>–Zn­(II) and, via intermolecular ionic contacts, twist the ligand’s pyridine rings into a left-handed (<i>M</i>) propeller (circular dichroism spectroscopy). With molecular baskets embodying the second coordination sphere about metal-containing TPAs, the here described findings should be useful for extending the catalytic function and chiral discrimination capability of TPAs

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

Design, Preparation, and Study of Catalytic Gated Baskets

We report a diastereoselective synthetic method to obtain a family of catalytic molecular baskets containing a spacious cavity (∼570 ų). These supramolecular catalysts were envisioned, via the process of gating, to control the access of substrates to the embedded catalytic center and thereby modulate the outcome of chemical reactions. In particular, gated basket <b>1</b> comprises a porphyrin “floor” fused to four phthalimide “side walls” each carrying a revolving aromatic “gate”. With the assistance of ¹H NMR and UV–vis spectroscopy, we demonstrated that the small 1-methylimidazole guest (<b>12</b>, 94 ų) would coordinate to the interior while the larger 1,5-diadamantylimidazole guest (<b>14</b>, 361 ų) is relegated to the exterior of basket Zn­(II)–<b>1</b>. Subsequently, we examined the epoxidation of differently sized and shaped alkenes <b>18</b>–<b>21</b> with catalytic baskets <b>12</b>_in–Mn­(III)–<b>1</b> and <b>14</b>_out–Mn­(III)–<b>1</b> in the presence of the sacrificial oxidant iodosylarene. The epoxidation of <i>cis</i>-stilbene occurred in the cavity of <b>14</b>_out–Mn­(III)–<b>1</b> and at the outer face of <b>12</b>_in–Mn­(III)–<b>1</b> with the stereoselectivity of the two transformations being somewhat different. Importantly, catalytic basket <b>14</b>_out–Mn­(III)–<b>1</b> was capable of kinetically resolving an equimolar mixture of <i>cis</i>-2-octene <b>20</b> and <i>cis</i>-cyclooctene <b>21</b> via promotion of the transformation in its cavity

Dual-Cavity Basket Promotes Encapsulation in Water in an Allosteric Fashion

We prepared dual-cavity basket <b>1</b> to carry six (<i>S</i>)-alanine residues at the entrance of its two juxtaposed cavities (289 ų). With the assistance of ¹H NMR spectroscopy and calorimetry, we found that <b>1</b> could trap a single molecule of <b>4</b> (<i>K</i>₁ = 1.45 ± 0.40 × 10⁴ M^–1, ITC), akin in size (241 ų) and polar characteristics to nerve agent VX (289 ų). The results of density functional theory calculations (DFT, M06-2X/6-31G*) and experiments (¹H NMR spectroscopy) suggest that the negative homotropic allosterism arises from the guest forming C–H···π contacts with all three of the aromatic walls of the occupied basket’s cavity. In response, the other cavity increases its size and turns rigid to prevent the formation of the ternary complex. A smaller guest <b>6</b> (180 ų), akin in size and polar characteristics to soman (186 ų), was also found to bind to dual-cavity <b>1</b>, although giving both binary [<b>1</b>⊂<b>6</b>] and ternary [<b>1</b>⊂<b>6</b>₂] complexes (<i>K</i>₁ = 7910 M^–1 and <i>K</i>₂ = 2374 M^–1, ¹H NMR spectroscopy). In this case, the computational and experimental (¹H NMR spectroscopy) results suggest that only two aromatic walls of the occupied basket’s cavity form C–H···π contacts with the guest to render the singly occupied host flexible enough to undergo additional structural changes necessary for receiving another guest molecule. The structural adaptivity of dual-cavity baskets of type <b>1</b> is unique and important for designing multivalent hosts capable of effectively sequestering targeted guests in an allosteric manner to give stable supramolecular polymers

Assembly and Folding of Twisted Baskets in Organic Solvents

A synthetic method for obtaining enantiopure and twisted baskets of type (<i>P</i>)-<b>3</b> is described. These chiral cavitands were found to fold quinoline gates, at the rim of their twisted platform, in acetonitrile and give molecular capsules that assemble into large unilamellar vesicles. In a less polar dichloromethane, however, cup-shaped (<i>P</i>)-<b>3</b> packed into vesicles but with the quinoline gates in an unfolded orientation. The ability of twisted baskets to form functional nanostructured materials could be of interest for building stereoselective sensors and catalysts

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