Self-assembled tetrazine cryptophane for ion pair recognition and guest release by cage disassembly.

Hereby, we describe the synthesis of a self-assembled -cryptophane using dynamic nucleophilic aromatic substitution of tetrazines. H NMR cage titrations reveal that the tetramethylammonium cation binds under slow exchange conditions while counter-anions show a fast exchange regime. Finally, the cryptophane can be disassembled by the addition of thiols allowing guest release.

A Cyclotriveratrylene Solvent-Dependent Chiral Switch.

Chiral molecular switches are attracting attention as they could pave the way to chiral molecular machines. Herein, we report on the design and synthesis of a single molecule chiral switch based on a cyclotriveratrylene scaffold, in which the chirality inversion is controlled by the solvent. Hemicryptophanes are built around a C cyclotriveratrylene chiral unit, with either M or P handedness, connected to another tripod and usually displaying an "out" configuration.

Probing the Importance of Host Symmetry on Carbohydrate Recognition.

The design of molecular cages with low symmetry could allow for more specific tuning of their properties and better mimic the unsymmetrical and complex environment of protein pockets. However, the added value of lowering symmetry of molecular receptors has been rarely demonstrated. Herein, C - and C -symmetrical cages, presenting the same recognition sites, have been synthesized and investigated as hosts for carbohydrate recognition.

A Dual Anchoring Strategy for the Directed Evolution of Improved Artificial Transfer Hydrogenases Based on Carbonic Anhydrase.

Artificial metalloenzymes result from anchoring a metal cofactor within a host protein. Such hybrid catalysts combine the selectivity and specificity of enzymes with the versatility of (abiotic) transition metals to catalyze new-to-nature reactions in an evolvable scaffold. With the aim of improving the localization of an arylsulfonamide-bearing iridium-pianostool catalyst within human carbonic anhydrase II (hCAII) for the enantioselective reduction of prochiral imines, we introduced a covalent linkage between the host and the guest.

An original self-assembly using a tetrathiafulvalene-based molecular clip for the recognition of fullerene C.

A glycoluril-based molecular clip incorporating two tetrathiafulvalene (TTF) sidewalls has been synthesized using a straightforward Diels-Alder synthetic route and its ability to self-assemble with fullerene C60 in a 2 : 1 stoichiometry has been demonstrated in solution.

Chemical Optimization of Whole-Cell Transfer Hydrogenation Using Carbonic Anhydrase as Host Protein.

Artificial metalloenzymes combine a synthetic metallocofactor with a protein scaffold and can catalyze abiotic reactions . Herein, we report on our efforts to valorize human carbonic anhydrase II as a scaffold for whole-cell transfer hydrogenation. Two platforms were tested: periplasmic compartmentalization and surface display in .

The Emergence of Anion-π Catalysis.

The objective of this Account is to summarize the first five years of anion-π catalysis. The general idea of anion-π catalysis is to stabilize anionic transition states on aromatic surfaces. This is complementary to the stabilization of cationic transition states on aromatic surfaces, a mode of action that occurs in nature and is increasingly used in chemistry.

Anion-π Catalysis of Diels-Alder Reactions.

Among concerted cycloadditions, the Diels-Alder reaction is the grand old classic, which is usually achieved with acid catalysis. In this report, hydroxypyrones, oxa-, and thiazolones are explored because they provide access to anionic dienes. Their [4+2] cycloaddition with cyclic and acyclic dienophiles, such as maleimides and fumarates, affords bicyclic products with four new stereogenic centers.

Anion-π catalysis: bicyclic products with four contiguous stereogenic centers from otherwise elusive diastereospecific domino reactions on π-acidic surfaces.

Anion-π interactions have been introduced recently to catalysis. The idea of stabilizing anionic intermediates and transition states on π-acidic surfaces is a new fundamental concept. By now, examples exist for asymmetric enolate, enamine, iminium and transamination chemistry, and the first anion-π enzyme has been created.

Anion-π Enzymes.

In this report, we introduce artificial enzymes that operate with anion-π interactions, an interaction that is essentially new to nature. The possibility to stabilize anionic intermediates and transition states on an π-acidic surface has been recently demonstrated, using the addition of malonate half thioesters to enolate acceptors as a biologically relevant example. The best chiral anion-π catalysts operate with an addition/decarboxylation ratio of 4:1, but without any stereoselectivity.

Interfacing Functional Systems.

The objective of molecular systems engineering is to move beyond functional components and primary systems, towards cumulate emergent properties in interfaced higher-order systems of unprecedented multifunctionality and sophistication.

Asymmetric Anion-π Catalysis of Iminium/Nitroaldol Cascades To Form Cyclohexane Rings with Five Stereogenic Centers Directly on π-Acidic Surfaces.

Anion-π interactions have been introduced to catalysis only recently, and evidence for their significance is so far limited to one classical model reaction in enolate and enamine chemistry. In this report, asymmetric anion-π catalysis is achieved for the first time for a more demanding cascade process. The selected example affords six-membered carbocycles with five stereogenic centers in a single step from achiral and acyclic substrates.

Unorthodox Interactions at Work.

This Perspective elaborates on the currently unfolding interest in integrating unorthodox non-covalent interactions into functional systems. Initial emphasis is on anion-π interactions at work, particularly in catalysis. Recent highlights are described in comparison to a coinciding renaissance of the more conventional, charge-inverted cation-π catalysis.

Anion-π Catalysis of Enolate Chemistry: Rigidified Leonard Turns as a General Motif to Run Reactions on Aromatic Surfaces.

To integrate anion-π, cation-π, and ion pair-π interactions in catalysis, the fundamental challenge is to run reactions reliably on aromatic surfaces. Addressing a specific question concerning enolate addition to nitroolefins, this study elaborates on Leonard turns to tackle this problem in a general manner. Increasingly refined turns are constructed to position malonate half thioesters as close as possible on π-acidic surfaces.

Asymmetric Anion-π Catalysis: Enamine Addition to Nitroolefins on π-Acidic Surfaces.

Here we provide experimental evidence for anion-π catalysis of enamine chemistry and for asymmetric anion-π catalysis. A proline for enamine formation on one side and a glutamic acid for nitronate protonation on the other side are placed to make the enamine addition to nitroolefins occur on the aromatic surface of π-acidic naphthalenediimides. With increasing π acidity of the formally trifunctional catalysts, rate and enantioselectivity of the reaction increase.

Glycoluril-tetrathiafulvalene molecular clips: on the influence of electronic and spatial properties for binding neutral accepting guests.

Glycoluril-based molecular clips incorporating tetrathiafulvalene (TTF) sidewalls have been synthesized through different strategies with the aim of investigating the effect of electrochemical and spatial properties for binding neutral accepting guests. We have in particular focused our study on the spacer extension in order to tune the intramolecular TTF···TTF distance within the clip and, consequently, the redox behavior of the receptor. Carried out at different concentrations in solution, electrochemical and spectroelectrochemical experiments provide evidence of mixed-valence and/or π-dimer intermolecular interactions between TTF units from two closed clips.

Fused glycoluril-tetrathiafulvalene molecular clips as receptors for neutral electron acceptor guests.

Glycoluril-based molecular clips incorporating tetrathiafulvalene (TTF) sidewalls have been synthesized, and the efficient binding ability in solution of this host architecture toward m-dinitrobenzene through donor-acceptor interaction has been demonstrated.