Multifarious Polymorphism of a Multiblock Amphiphilic Macrocycle Bearing Thermally Responsive Polyether Segment

Formation of multiple crystalline phases of a multiblock amphiphilic macrocycle <b>AT2B</b> is demonstrated. <b>AT2B</b> forms a single crystal (Cr-α) by vapor diffusion and shows reversible single-crystal-to-single-crystal transition between two crystalline phases (Cr-α and Cr-β) by a temperature change, and crystalline <b>AT2B</b> (Cr-β) melts at 422 K, and the cooling rate from the melt influences the phase of the solid formed. By cooling at 1.0 K min^–1, <b>AT2B</b> forms crystalline phases (Cr-γ and Cr-δ), which are different from both Cr-α and Cr-β. On the other hand, cooling at 2.0 K min^–1 results in the formation of an amorphous phase, and a mechanical stress also triggers a crystal-to-amorphous solid transition. Interestingly, the amorphous solid crystallizes to give the fifth crystalline phase (Cr-γ) upon heating before melting. It is suggested that these multiple phase transitions are driven by thermal conformational changes at the tetraethylene glycol chains of <b>AT2B</b>

Contrasting Topological Effect of PEG-Containing Amphiphiles to Natural Lipids on Stability of Vesicles

Topology of amphiphiles is important to control physicochemical properties of supramolecular assemblies. Nature demonstrates higher stability of membrane composed of lipids with a macrocyclic aliphatic tail than those with linear tails, which likely results from the restricted molecular structures of the macrocyclic lipids, allowing for closer molecular packing. In contrast, here we report that a PEG-containing macrocyclic amphiphile shows lower stability of vesicles than the corresponding acyclic one. The macrocyclic amphiphile consists of an aromatic hydrophobic part with chirality in which both ends are strapped by octaethylene glycol via phosphoric ester groups, while the acyclic amphiphile bears tetraethylene glycol chains attached to both ends of the hydrophobic part. Because of the thermoresponsive property of PEG to change its conformation, the hydrophobic part of the macrocyclic amphiphile undergoes a larger thermal conformational change than that of the acyclic one. In addition, the cyclic amphiphile has a larger molecular area, which likely reduces the vesicular stability compared with the acyclic one. Such a contrasting topological effect caused by macrocyclization at the aliphatic part seen in the natural system and at the hydrophilic part demonstrated in this study leads to expand the molecular design of amphiphiles for both increasing and decreasing the stability of vesicles by molecular topology

A plausible reaction mechanism of the intra- and intermolecular nucleophilic substitutions to prompt transetherification.

<p>A plausible reaction mechanism of the intra- and intermolecular nucleophilic substitutions to prompt transetherification.</p

Ether formation between 1 and 2.

<p>Ether formation between 1 and 2.</p

Ether formation between tetraethylene glycol tosylate 2a and a) monoalcohol 8, b) propane-1,3-diol 11 and c) 2-(hydroxymethyl)propane-1,3-diol 13.

<p>Reaction time was 12 h. Yields were calculated based on the isolated amounts. ND: not detected.</p

MALDI-TOF-MS spectrum of the crude product extracted by CHCl₃ for the reaction in Table 1, Entry 1.

<p>Structures of 6 and 7 are shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0091912#pone-0091912-g003" target="_blank">Figure 3</a>. Matrix: α-cyano-4-hydroxycinnamic acid.</p

Mechano-Sensitive Synthetic Ion Channels

Mechanical stress is a ubiquitous stimulus sensed by membrane proteins, but rarely by synthetic molecules. Inspired by mechano-sensitive ion channels found in cell membranes, tension-responsive transmembrane multiblock amphiphiles were developed. In membranes, a single-transmembrane amphiphile responds to both expanding and contracting tensions to weaken and strengthen the stacking of membrane-spanning units, respectively, and ion transportation is triggered by expanding tension to form a supramolecular channel, while little transportation is observed under a tensionless condition. In contrast, a three-transmembrane amphiphile showed little spectroscopic response to tensions, likely due to weaker stacking of membrane-spanning units than in the single-transmembrane amphiphile. Nevertheless, the three-transmembrane amphiphile shows ion transportation by forming a unimolecular channel even under a tensionless condition, and the ion-transporting activity decreased with expanding tension. Interestingly, the estimated operating force of these synthetic systems was comparable to that of the mechano-sensitive proteins. This study opens the door toward new mechano-sensitive molecular devices

Ion Permeation by a Folded Multiblock Amphiphilic Oligomer Achieved by Hierarchical Construction of Self-Assembled Nanopores

A multiblock amphiphilic molecule <b>1</b>, with a tetrameric alternating sequence of hydrophilic and hydrophobic units, adopts a folded structure in a liposomal membrane like a multipass transmembrane protein, and is able to transport alkali metal cations through the membrane. Hill’s analysis and conductance measurements, analyzed by the Hille equation, revealed that the tetrameric assembly of <b>1</b> forms a 0.53 nm channel allowing for permeation of cations. Since neither <b>3</b>, bearing flexible hydrophobic units and forming no stacked structures in the membrane, nor <b>2</b>, a monomeric version of <b>1</b>, is able to transport cations, the folded conformation of <b>1</b> in the membrane is likely essential for realizing its function. Thus, function and hierarchically formed higher-order structures of <b>1</b>, is strongly correlated with each other like proteins and other biological macromolecules

Reversible Ion Transportation Switch by a Ligand-Gated Synthetic Supramolecular Ion Channel

Inspired by the regulation of cellular activities found in the ion channel proteins, here we developed membrane-embedded synthetic chiral receptors <b>1</b> and <b>2</b> with different terminal structures, where receptor <b>1</b> has hydrophobic triisopropylsilyl (TIPS) groups and receptor <b>2</b> has hydrophilic hydroxy groups. The receptors have ligand-binding units that interact with cationic amphiphiles such as 2-phenethylamine (PA). Conductance study revealed that the receptors hardly show ion transportation at the ligand-free state. After ligand binding involving a conformational change, receptor <b>1</b> bearing TIPS termini displays a significant current enhancement due to ion transportation. The current substantially diminishes upon addition of β-cyclodextrin (βCD) that scavenges the ligand from the receptor. Importantly, the receptor again turns into the conductive state by the second addition of PA, and the activation/deactivation of the ion transportation can be repeated. In contrast, receptor <b>2</b> bearing the hydroxy terminal groups hardly exhibits ion transportation, suggesting the importance of terminal TIPS groups of <b>1</b> that likely anchor the receptor in the membrane

Micrometer-Size Vesicle Formation Triggered by UV Light

Vesicle formation is a fundamental kinetic process related to the vesicle budding and endocytosis in a cell. In the vesicle formation by artificial means, transformation of lamellar lipid aggregates into spherical architectures is a key process and known to be prompted by e.g. heat, infrared irradiation, and alternating electric field induction. Here we report UV-light-driven formation of vesicles from particles consisting of crumpled phospholipid multilayer membranes involving a photoactive amphiphilic compound composed of 1,4-bis­(4-phenylethynyl)­benzene (BPEB) units. The particles can readily be prepared from a mixture of these components, which is casted on the glass surface followed by addition of water under ultrasonic radiation. Interestingly, upon irradiation with UV light, micrometer-size vesicles were generated from the particles. Neither infrared light irradiation nor heating prompted the vesicle formation. Taking advantage of the benefits of light, we successfully demonstrated micrometer-scale spatiotemporal control of single vesicle formation. It is also revealed that the BPEB units in the amphiphile are essential for this phenomenon