Yves-Marie Legrand

Imidazole‐Quartet Water and Proton Dipolar Channels

Powerful synthetic scaffolds mimicking natural proteinfunctions unlock the door to a world of interactive materialsparalleling that of biology. Numerous artificial systemsshowing a rich array of interconverting ion-channel conduc-tance states in phospholipid and polymeric membranes havebeen developed in the last decades.

Dynamic hybrid materials for constitutional self-instructed membranes.

Constitutional self-instructed membranes were developed and used for mimicking the adaptive structural functionality of natural ion-channel systems. These membranes are based on dynamic hybrid materials in which the functional self-organized macrocycles are reversibly connected with the inorganic silica through hydrophobic noncovalent interactions. Supramolecular columnar ion-channel architectures can be generated by reversible confinement within scaffolding hydrophobic silica mesopores. They can be structurally determined by using X-ray diffraction and morphologically tuned by alkali-salts templating. From the conceptual point of view, these membranes express a synergistic adaptive behavior: the simultaneous binding of the fittest cation and its anion would be a case of “homotropic allosteric interactions,” because in time it increases the transport efficiency of the pore-contained superstructures by a selective evolving process toward the fittest ion channel. The hybrid membranes presented here represent dynamic constitutional systems evolving over time to form the fittest ion channels from a library of molecular and supramolecular components, or selecting the fittest ion pairs from a mixture of salts demonstrating flexible adaptation.

Single-Crystal X-ray Structure of 1,3-Dimethylcyclobutadiene by Confinement in a Crystalline Matrix

Snapshot of a Strained Ring Benzene and cyclobutadiene possess diametrically opposed properties. The former, a hexagonal hydrocarbon with a geometry perfectly suited to its bonding arrangement, exhibits unusual stability. The latter, with its two fewer carbons tightly squeezed into the right angles of a 4-membered ring, rapidly forms a dimer to relieve its considerable geometric and electronic strain. Monomeric cyclobutadiene was first isolated in substantial quantity by confining it within a molecular shell, but it has eluded full structural characterization. Legrand et al. (p. 299) have now found a host lattice that stabilizes a dimethyl-substituted derivative of the molecule sufficiently to allow analysis of its structure and bonding motif by x-ray diffraction. A normally unstable hydrocarbon has been trapped and structurally characterized within a host crystal. Cyclobutadiene (CBD), the smallest cyclic hydrocarbon bearing conjugated double bonds, has long intrigued chemists on account of its strained geometry and electronic instability, but the parent compound and its unperturbed derivatives have thus far eluded crystallographic characterization. In this work, we immobilize a precursor, 4,6-dimethyl-α-pyrone, in a guanidinium-sulfonate-calixarene (G4C) crystalline network that confines the guest through a combination of CH-π and hydrogen-bond interactions. Ultraviolet irradiation of the crystals transforms the entrapped 4,6-dimethyl-α-pyrone into a 4,6-dimethyl-β-lactone Dewar intermediate that is sufficiently stable under the confined conditions at 175 kelvin to allow a conventional structure determination by x-ray diffraction. Further irradiation pushes the reaction to completion, enabling the structure determination of 1,3-dimethylcyclobutadiene Me2CBD. Our data support experimental observation of square-planar (Me2CBDS) and rectangular-bent (Me2CBDR) geometries in the G4C host matrix. The hydrogen-bonded, dissociated carbon dioxide coproduct interacts more strongly with Me2CBDS than with Me2CBDR.

Highly Selective Artificial Cholesteryl Crown Ether K(+)-Channels.

The bacterial KcsA channel conducts K(+) cations at high rates while excluding Na(+) cations. Herein, we report an artificial ion-channel formed by H-bonded stacks of crown-ethers, where K(+) cation conduction is highly preferred to Na(+) cations. The macrocycles aligned along the central pore surround the K(+) cations in a similar manner to the water around the hydrated cation, compensating for the energetic cost of their dehydration. In contrast, the Na(+) cation does not fit the macrocyclic binding sites, so its dehydration is not completely compensated. The present highly K(+)-selective macrocyclic channel may be regarded as a biomimetic of the KcsA channel.

Self-sorting of metallosupramolecular DCLs via double-level exchange: amplification in solution and solid state modulation

Interexchanging metallosupramolecular double level imine/ligand Dynamic Constitutional Libraries (DCLs), produce, in solution, the amplification of heteroleptic complexes, which convert into homoleptic complexes via constitutional crystallization.

Squalyl Crown Ether Self-Assembled Conjugates: An Example of Highly Selective Artificial K(+) Channels.

The natural KcsA K+ channel, one of the best-characterized biological pore structures, conducts K+ cations at high rates while excluding Na+ cations. The KcsA K+ channel is of primordial inspiration for the design of artificial channels. Important progress in improving conduction activity and K+ /Na+ selectivity has been achieved with artificial ion-channel systems. However, simple artificial systems exhibiting K+ /Na+ selectivity and mimicking the biofunctions of the KcsA K+ channel are unknown. Herein, an artificial ion channel formed by H-bonded stacks of squalyl crown ethers, in which K+ conduction is highly preferred to Na+ conduction, is reported. The K+ -channel behavior is interpreted as arising from discreet stacks of dimers resulting in the formation of oligomeric channels, in which transport of cations occurs through macrocycles mixed with dimeric carriers undergoing dynamic exchange within the bilayer membrane. The present highly K+ -selective macrocyclic channel can be regarded as a biomimetic alternative to the KcsA channel.

Homomeric and heteromeric self-assembly of hybrid ureido–imidazole compounds

The H-bond mediated self-assembly of hybrid ureido–imidazole compounds has shown that the relative spatial position of the H-bonding groups directs homomeric or heteromeric association of the molecules in the solid state.

New "pyrene box" cages for adaptive guest conformations.

The possibility of controlling the compression extent and the coiling shape of the 1,12-diammoniumdodecane guest is shown by changing the dimensions of the internal space of the host guanidinium 1,3,5,8 pyrene-tetrasulfonate PTS(4-) crystalline capsules by using guanidinium (G(+)), amino-guanidinium (AG(+)), and diaminoguanidinium (A2G(+)) cations.

Bis-15-crown-5-ether-pillar[5]arene K+-Responsive Channels

An artificial selective K+ channel is formed from the supramolecular organization on bis(benzo-15-crown-5- ether-ureido)-pillar[5]arene compound. This channel achieves a selectivity of SK+/Na+ = 5 for an initial transport rate of kK+ = 3.2 × 10-3 s-1. The cation-file diffusion occurs via selective macrocyclic-filters anchored on inactive supporting pillar[5]arene relays. The sandwich-type binding geometry of the K+ cation by two 15-crown-5 moieties sites is a key feature influencing channel efficiency.

Oriented chiral water wires in artificial transmembrane channels

Chiral dipolar oriented water wires are observed inside artificial water channels embedded in supported bilayer membranes. Aquaporins (AQPs) feature highly selective water transport through cell membranes, where the dipolar orientation of structured water wires spanning the AQP pore is of considerable importance for the selective translocation of water over ions. We recently discovered that water permeability through artificial water channels formed by stacked imidazole I-quartet superstructures increases when the channel water molecules are highly organized. Correlating water structure with molecular transport is essential for understanding the underlying mechanisms of (fast) water translocation and channel selectivity. Chirality adds another factor enabling unique dipolar oriented water structures. We show that water molecules exhibit a dipolar oriented wire structure within chiral I-quartet water channels both in the solid state and embedded in supported lipid bilayer membranes (SLBs). X-ray single-crystal structures show that crystallographic water wires exhibit dipolar orientation, which is unique for chiral I-quartets. The integration of I-quartets into SLBs was monitored with a quartz crystal microbalance with dissipation, quantizing the amount of channel water molecules. Nonlinear sum-frequency generation vibrational spectroscopy demonstrates the first experimental observation of dipolar oriented water structures within artificial water channels inserted in bilayer membranes. Confirmation of the ordered confined water is obtained via molecular simulations, which provide quantitative measures of hydrogen bond strength, connectivity, and the stability of their dipolar alignment in a membrane environment. Together, uncovering the interplay between the dipolar aligned water structure and water transport through the self-assembled I-quartets is critical to understanding the behavior of natural membrane channels and will accelerate the systematic discovery for developing artificial water channels for water desalting.