Green and Effective Preparation of α-Hydroxyphosphonates by Ecocatalysis.

A green and effective approach for the synthesis of structurally diversed α-hydroxyphosphonates via hydrophosphonylation of aldehydes under solventless conditions and promoted by biosourced catalysts, called ecocatalysts "Eco-MgZnOx" is presented. Ecocatalysts were prepared from Zn-hyperaccumulating plant species Arabidopsis halleri, with simple and benign thermal treatment of leaves rich in Zn, and without any further chemical treatment. The elemental composition and structure of Eco-MgZnOx were characterized by MP-AES, XRPD, HRTEM, and STEM-EDX techniques. These analyses revealed a natural richness in two unusual and valuable mixed zinc-magnesium and iron-magnesium oxides. The ecocatalysts were employed in this study to demonstrate their potential use in hydrophosphonylation of aldehydes, leading to various α-hydroxyphosphonate derivatives, which are critical building blocks in the modern chemical industry. Computational chemistry was performed to help discriminate the role of some of the constituents of the mixed oxide ecocatalysts. High conversions, broad substrate scope, mild reaction conditions, and easy purification of the final products together with simplicity of the preparation of the ecocatalysts are the major advantages of the presented protocol. Additionally, Eco-MgZnOx-P could be recovered and reused for up to five times.

Mechanochemistry and Eco-Bases for Sustainable Michael Addition Reactions.

The Michael addition reaction was revisited with a full focus on sustainability combined with efficiency, using mechanochemistry in mild conditions. First, the synthesis of cyclopentenone derivatives was chosen as a model reaction to find optimal conditions in mechanochemistry while using classical but weak bases. The reaction was efficient (84-95% yields), fast (2-6 h), solvent free, and required 0.1 equivalent of base. Aiming to reach greener conditions, classical bases were then replaced using new bio-sourced bases, called Eco-bases, that were easily prepared from plants and led to heterogeneous catalysts. The composition and structure of Eco-bases were characterized by MP-AES, XRPD, EBSD/EDS, HRTEM/EDX and ion chromatography. Interestingly, a high ratio of potassium was observed with the presence of K2Ca(CO3)2 for the most effective Eco-base. The new Eco-bases were used for the mechanical-assisted construction of functionalized alkenone derivatives. The versatility of the method has been successfully applied with good to excellent yields to different Michael donors and acceptors. Eco-bases were recycled and reused four times with the same performances. Combining Eco-bases and mechanochemistry in Michael addition reactions allowed reaching a maximum degree of sustainability (efficient, rapid, low catalyst loading, solvent-free reactions with bio-sourced catalysts) and participating in the development of mechanochemistry in sustainable chemistry.

The Unexpected Helical Supramolecular Assembly of a Simple Achiral Acetamide Tecton Generates Selective Water Channels.

Invited for the cover of this issue is the collaborative research team coordinated by Arie van der Lee at the University of Montpellier. The image depicts chiral channels with highly mobile water molecules resulting from the robust self-organization of a simple achiral acetamide. Fully reversible release and re-uptake of water molecules takes place near ambient conditions, with efficient water transport and a good selectivity against NaCl suggesting it to be an efficient candidate for desalination processes. Read the full text of the article at 10.1002/chem.20200383.

The Unexpected Helical Supramolecular Assembly of a Simple Achiral Acetamide Tecton Generates Selective Water Channels.

Achiral 2-hydroxy-N-(diphenylmethyl)acetamide (HNDPA) crystallizes in the P61 chiral space group as a hydrate, building up permeable chiral crystalline helical water channels. The crystallization-driven chiral self-resolution process is highly robust, with the same air-stable crystalline form readily obtained under a variety of conditions. Interestingly, the HNDPA supramolecular helix inner pore is filled by a helical water wire. The whole edifice is mainly stabilized by robust hydrogen bonds involving the HNDPA amide bonds and CH… π interactions between the HNDPA phenyl groups. The crystalline structure shows breathing behavior, with completely reversible release and re-uptake of water inside the chiral channel under ambient conditions. Importantly, the HNDPA channel is able to transport water very efficiently and selectively under biomimetic conditions. With a permeability per channel of 3.3 million water molecules per second in large unilamellar vesicles (LUV) and total selectivity against NaCl, the HNDPA channel is a very promising functional nanomaterial for future applications.

Eco-Friendly Methodology for the Formation of Aromatic Carbon-Heteroatom Bonds by Using Green Ionic Liquids.

A new sustainable method is reported for the formation of aromatic carbon-heteroatom bonds under solvent-free and mild conditions (no co-oxidant, no strong acid and no toxic reagents) by using a new type of green ionic liquid. The bromination of methoxy arenes was chosen as a model reaction. The reaction methodology is based on only using natural sodium bromine, which is transformed into an electrophilic brominating reagent within an ionic liquid, easily prepared from the melted salt FeCl3 hexahydrate. Bromination reactions with this in-situ-generated reagent gave good yields and excellent regioselectivity under simple and environmentally friendly conditions. To understand the unusual bromine polarity reversal of sodium bromine without any strong oxidant, the molecular structure of the reaction medium was characterised by Raman and direct infusion electrospray ionisation mass spectroscopy (ESI-MS). An extensive computational investigation using density functional theory methods was performed to describe a mechanism that suggests indirect oxidation of Br- through new iron adducts. The versatility of the methodology was successively applied to nitration and thiocyanation of methoxy arenes using KNO3 and KSCN in melted hexahydrated FeCl3 .

Manipulation of Transmembrane Transport by Synthetic K+ Ionophore Depsipeptides and Its Implications in Glucose-Stimulated Insulin Secretion in ß-Cells.

The cyclic depsipeptide cereulide toxin it is a very well-known potassium electrogenic ionophore particularly sensitive to pancreatic beta cells. The mechanistic details of its specific activity are unknown. Here, we describe a series of synthetic substituted cereulide potassium ionophores that cause impressive selective activation of glucose-induced insulin secretion in a constitutive manner in rat insulinoma INS1E cells. Our study demonstrates that the different electroneutral K+ transport mechanism exhibited by the anionic mutant depsipeptides when compared with classical electrogenic cereulides can have an important impact of pharmacological value on glucose-stimulated insulin secretion.

Imidazole derivatives as artificial water channel building-blocks: structural design influence on water permeability.

A series of mono- and di-ureidoethylimidazole derivatives were tested as self-assembled supramolecular channels for water transport. Several structural behaviours were compared in order to gain insight on the structure-water transport activity relationship. The three main features that are critical to tailor artificial water channel building blocks are: (i) the selectivity of the hydrophilic head, (ii) the H-bonding scaffold favouring the directional self-assembly, and (iii) the lipophilic tail for the compatibility with the hydrophobic environment of the lipid bilayer. The designed compounds bear one or two imidazole heads, one or two urea moieties, and different lipophilic tails. Water transport experiments were performed in order to assess the critical parameters. For that, large unilamellar vesicles (LUV) were fabricated using a mixture of phosphatidylcholine, phosphatidylserine and cholesterol. The bilayer of the LUV constituted a membrane between an intra and an extra vesicular medium. The artificial water channel candidates are put in the presence of this membrane to improve its water permeability. The permeation of elements other than water is ideally maintained to a minimum in order to achieve selective water filtration. In this study the effect of additional urea moieties, as well as its absence, was evidenced as detrimental for the permeation and the influence of the tail was also investigated.

Structure-Driven Selection of Adaptive Transmembrane Na+ Carriers or K+ Channels.

Self-assembled alkyl-ureido-benzo-15-crown-5-ethers are selective ionophores for K+ cations, which are preferred to Na+ cations. The transport mechanism is determined by the optimal coordination rather than classical dimensional compatibility between the crown ether hole and the cation diameter. Herein, we demonstrate that systematic changes of the structure lead to unexpected modifications in the cation-transport activity and suffice to produce adaptive selection. We show that the main contribution to performance arises from optimal constraints on the conformational freedom, which are determined by the binding macrocycles, the nature of the hydrogen-bonding groups, and the hydrophobic tails. Simple changes to the flexible 15-crown-5-ether lead to selective carriers for Na+ . Hydrophobic stabilization of the channels through mutual interactions between lipids and variable hydrophobic tails appears to be an important cause of increased activity. Oppositely, restricted translocation is achieved when constrained hydrogen-bonded macrocyclic relays are less dynamic in a pore superstructure.

Biosourced Polymetallic Catalysis: A Surprising and Efficient Means to Promote the Knoevenagel Condensation.

Zn hyperaccumulator (Arabidobsis halleri) and Zn accumulator Salix "Tordis" (Salix schwerinii × Salix viminalis) have shown their interest in the phytoextraction of polluted brownfields. Herein, we explore a novel methodology based on the chemical valorization of Zn-rich biomass produced by these metallophyte plants. The approach is based on the use of polymetallic salts derived from plants as bio-based catalysts in organic chemistry. The formed ecocatalysts were characterized via ICP-MS, X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) in order to precise the chemical composition, structure, and behavior of the formed materials. The Doebner-Knoevenagel reaction was chosen as model reaction to study their synthetic potential. Significant differences to usual catalysts such as zinc (II) chloride are observed. They can principally be related to a mixture of unusual mineral species. DFT calculations were carried out on these salts in the context of the Gutmann theory. They allow the rationalization of experimental results. Finally, these new bio-based polymetallic catalysts illustrated the interest of this concept for green and sustainable catalysis.

Oriented chiral water wires in artificial transmembrane channels.

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.

Hydrophobic metallo-supramolecular Pd2L4 cages for zwitterionic guest encapsulation in organic solvents.

Hydrophilic zwitterionic guest encapsulation by metallo-supramolecular cages through synergetic coordination, H-bonding and hydrophobic interactions.

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.

"Pyrene Box" Cages for the Confinement of Biogenic Amines.

The complete structure of non-crystalline compounds can be determined by confining them in crystalline structures. The reduced motional degrees of freedom of encapsulated guests can be obtained through their anchoring to the host cages, which results in the reduction of a significant amount of disorder. The "pyrene box" cages that easily crystallize from aqueous solutions are recommended to achieve complete structure elucidation of compounds of biological interest. In this study, the "pyrene box" cages have been used for the in situ encapsulation of biogenic amines: histamine, dopamine, and serotonin. NMR spectroscopy illustrates that these systems are stable in aqueous solution. The X-ray single-crystal structure analysis reveals that the pyrene box/biogenic amine systems are stabilized through combined interactions, strongly contributing to in situ fixation and accurate determination of their crystal structures.

Dynameric host frameworks for the activation of lipase through H-bond and interfacial encapsulation.

A facile lipase activation has been achieved by direct addition of multivalent amide dynameric frameworks into the reaction aqueous solutions, through the combined effects of lipase-host matrices, H-bonds and interfacial interactions.

Adaptive Encapsulation of ω-Amino Acids and Their Guanidinium-Amide Congeners.

The binding and the encapsulation of the 6-aminohexanoic acid (1) and 11-aminoundecanoic acid (2) are achieved in aqueous solution and in crystalline Pyrene-box cages. Unexpectedly, the amino-guanidinium AG+ and the amino acids 1 or 2 are reacting in aqueous solution in the absence and in the presence of Pyrene-box cages. The formation of an amide bond between a carboxylic acid and the amino-guanidine unit under mild acidic conditions in water without the use a coupling reagent is extremely interesting and unexpected. The resulted adducts AG1 and AG2 show adaptive binding behaviors and compressions.

Salt-Excluding Artificial Water Channels Exhibiting Enhanced Dipolar Water and Proton Translocation.

Aquaporins (AQPs) are biological water channels known for fast water transport (∼10(8)-10(9) molecules/s/channel) with ion exclusion. Few synthetic channels have been designed to mimic this high water permeability, and none reject ions at a significant level. Selective water translocation has previously been shown to depend on water-wires spanning the AQP pore that reverse their orientation, combined with correlated channel motions. No quantitative correlation between the dipolar orientation of the water-wires and their effects on water and proton translocation has been reported. Here, we use complementary X-ray structural data, bilayer transport experiments, and molecular dynamics (MD) simulations to gain key insights and quantify transport. We report artificial imidazole-quartet water channels with 2.6 Špores, similar to AQP channels, that encapsulate oriented dipolar water-wires in a confined chiral conduit. These channels are able to transport ∼10(6) water molecules/s, which is within 2 orders of magnitude of AQPs' rates, and reject all ions except protons. The proton conductance is high (∼5 H(+)/s/channel) and approximately half that of the M2 proton channel at neutral pH. Chirality is a key feature influencing channel efficiency.

Dynamic encapsulation and activation of carbonic anhydrase in multivalent dynameric host matrices.

A straight-forward carbonic anhydrase activation strategy via dynamic encapsulation has been achieved by direct addition of multivalent amide dynamers into enzyme reaction solutions.

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.