Transition Metals Coordination by Bis-imidazole-calix[4]arene Ligands with and Without Pyrene Units Grafted at the Large Rim.

Herein, the presented results show that previously studied DNA/RNA-interacting bis-imidazole-calix[4]arene systems can, in aqueous solutions, efficiently bind a series of biorelevant transition metal cations by coordination with the two imidazole arms at the small rim of their macrocyclic basket. The SCXRD and NMR results structurally characterised the complexes formed by referent bis-imidazole-calix[4]arene with Cu and Zn. In solid-state (crystal), the bis-anilino derivative/Cu complex, only upon exposure to the air, undergoes intramolecular dehydrogenative coupling of two neighbouring aniline units, yielding an azo bridge at the large rim of the calix[4]arene basket.

Synthesis of -Symmetrical 1,3,5-Tris-Protected Calix[6]arene-Based Molecular Platforms.

Few synthetic methodologies that yield tris-functionalized -symmetrical calix[6]arenes have been reported. In this work, three allyl protecting groups are selectively placed in 1,3,5 alternate positions of three pristine calix[6]arenes, each differing by their substituent on the large rim, resulting in three new -symmetrical molecular platforms. Removal of the protecting allylic groups gives access to sophisticated calix[6]arenes that can be further modified.

Novel pyrene-calix[4]arene derivatives as highly sensitive sensors for nucleotides, DNA and RNA.

Covalent functionalization of a calix[4]arene with one or two pyrene arms at one rim and two imidazoles at the opposite rim of the macrocyclic basket, yields fluorescent conjugates characterized by intramolecular pyrene-calixarene exciplex emission of a mono-pyrene conjugate, whereas the bis-pyrene derivative exhibits pyrene excimer fluorescence. The pyrene emission in these novel compounds is shown to be sensitive to non-covalent interactions with both mono- and polynucleotides. Pyrene-calixarene conjugates, acting as host molecules, strongly interact with nucleotides, as monitored by moderate emission quenching, reaching 0.

Selective Metal-ion Complexation of a Biomimetic Calix[6]arene Funnel Cavity Functionalized with Phenol or Quinone.

In the biomimetic context, many studies have evidenced the importance of the 1 and 2 coordination sphere of a metal ion for controlling its properties. Here, we propose to evaluate a yet poorly explored aspect, which is the nature of the cavity that surrounds the metal labile site. Three calix[6]arene-based aza-ligands are compared, that differ only by the nature of cavity walls, anisole, phenol or quinone (L , L and L ).

Dual Electroactivity in a Covalent Organic Network with Mechanically Interlocked Pillar[5]arenes.

The synthesis and characterization of a polyrotaxanated covalent organic network (CON) based on the association between the viologen and pillar[5]arene (P[5]OH) units are reported. The mechanical bond allows for the irreversible insertion of n-type redox centers (P[5]OH macrocycles) within a pristine structure based on p-type viologen redox centers. Both redox units are active on a narrow potential range and, in water, the presence of P[5]OH greatly increases the electroactivity of the material.

A Promising Approach for Controlling the Second Coordination Sphere of Biomimetic Metal Complexes: Encapsulation in a Dynamic Hydrogen-Bonded Capsule.

The design of biomimetic models of metalloenzymes needs to take into account many factors and is therefore a challenging task. We propose in this work an original strategy to control the second coordination sphere of a metal centre and its distal environment. A biomimetic complex, reproducing the first coordination sphere, is encapsulated in a self-assembled hydrogen-bonded capsule.

Photoinduced Electron Transfer Involving a Naphthalimide Chromophore in Switchable and Flexible [2]Rotaxanes.

The interlocking of ring and axle molecular components in rotaxanes provides a way to combine chromophoric, electron-donor and electron-acceptor moieties in the same molecular entity, in order to reproduce the features of photosynthetic reaction centers. To this aim, the photoinduced electron transfer processes involving a 1,8-naphthalimide chromophore, embedded in several rotaxane-based dyads, were investigated by steady-state and time-resolved absorption and luminescence spectroscopic experiments in the 300 fs-10 ns time window. Different rotaxanes built around the dialkylammonium/ dibenzo[24]crown-8 ether supramolecular motif were designed and synthesized to decipher the relevance of key structural factors, such as the chemical deactivation of the ammonium-crown ether recognition, the presence of a secondary site for the ring along the axle, and the covalent functionalization of the macrocycle with a phenothiazine electron donor.

Gating the electron transfer at a monocopper centre through the supramolecular coordination of water molecules within a protein chamber mimic.

Functionality of enzymes is strongly related to water dynamic processes. The control of the redox potential for metallo-enzymes is intimately linked to the mediation of water molecules in the first and second coordination spheres. Here, we report a unique example of supramolecular control of the redox properties of a biomimetic monocopper complex by water molecules.

Selective EPR Detection of Primary Amines in Water with a Calix[6]azacryptand-Based Copper(II) Funnel Complex.

A water-soluble calix[6]arene-based azacryptand was synthesized. The corresponding tren [tris(2-aminoethyl)amine] cap grafted at the small rim coordinates strongly a copper(II) ion over a wide range of pH. The host-guest properties of the complex were explored by EPR spectroscopy.

Remote electrochemical modulation of pK in a rotaxane by co-conformational allostery.

Allosteric control, one of Nature's most effective ways to regulate functions in biomolecular machinery, involves the transfer of information between distant sites. The mechanistic details of such a transfer are still an object of intensive investigation and debate, and the idea that intramolecular communication could be enabled by dynamic processes is gaining attention as a complement to traditional explanations. Mechanically interlocked molecules, owing to the particular kind of connection between their components and the resulting dynamic behavior, are attractive systems to investigate allosteric mechanisms and exploit them to develop functionalities with artificial species.

Thermodynamic Insights on a Bistable Acid-Base Switchable Molecular Shuttle with Strongly Shifted Co-conformational Equilibria.

Bistable [2]rotaxanes in which the affinities of the two stations can be reversed form the basis of molecular shuttles. Gaining quantitative information on such rotaxanes in which the ring distribution between the two stations is largely nonsymmetric has proven to be very challenging. Herein, we report on two independent experimental methodologies, based on luminescence lifetime measurements and acid-base titrations, to determine the relative populations of the two co-conformations of a [2]rotaxane.

An Artificial Molecular Transporter.

The transport of substrates is one of the main tasks of biomolecular machines in living organisms. We report a synthetic small-molecule system designed to catch, displace, and release molecular cargo in solution under external control. The system consists of a bistable rotaxane that behaves as an acid-base controlled molecular shuttle, whose ring component bears a tether ending with a nitrile group.

Kinetic and Thermodynamic Stabilization of Metal Complexes by Introverted Coordination in a Calix[6]azacryptand.

The Huisgen thermal reaction between an organic azide and an acetylene was employed for the selective monofunctionalization of a X6 -azacryptand ligand bearing a tren coordinating unit [X6 stands for calix[6]arene and tren for tris(2-aminoethyl)amine]. Supramolecular assistance, originating from the formation of a host-guest inclusion complex between the reactants, greatly accelerates the reaction while self-inhibition affords a remarkable selectivity. The new ligand possesses a single amino-leg appended at the large rim of the calixarene core and the corresponding Zn(2+) complex was characterized both in solution and in the solid state.

Supramolecular assistance for the selective demethylation of calixarene-based receptors.

The selective demethylation of methoxy groups of several multifunctionalized 1,3,5-trimethoxycalix[6]arene-based receptors has been achieved. It is shown in this study that the best reagent is trimethylsilyl iodide (TMSI) and that the conformation adopted by the calixarene core is crucial for both the selectivity and the efficiency of the process. A key feature appears to be the "in" or "out" orientation of the methoxy substituents relative to the macrocyclic cavity.

Biomimetic cavity-based metal complexes.

The design of biomimetic complexes for the modeling of metallo-enzyme active sites is a fruitful strategy for obtaining fundamental information and a better understanding of the molecular mechanisms at work in Nature's chemistry. The classical strategy for modeling metallo-sites relies on the synthesis of metal complexes with polydentate ligands that mimic the coordination environment encountered in the natural systems. However, it is well recognized that metal ion embedment in the proteic cavity has key roles not only in the recognition events but also in generating transient species and directing their reactivity.

A water-soluble calix[4]arene-based ligand for the selective linear coordination and stabilization of copper(I) ion in aerobic conditions.

A number of serious diseases are linked to copper homeostasis dysfunction. The design of copper(I)-selective chelators is of particular interest not only for the creation of therapeutic objects but also as useful tools to gain insights into the coordination of copper(I) in a biological medium. A water-soluble Cu(I)-selective ligand that associates strong Cu(I) binding at pH = 7.

A versatile strategy for appending a single functional group to a multifunctional host through host-guest covalent-capture.

Mono-functionalization of a molecular host is a key step for the development of various efficient systems ranging from supramolecular fluorescent probes to supramolecular catalysts. The presence of several identical reactive groups on the host makes its selective mono-functionalization a challenge. We propose a general two-step strategy to achieve this, based on the receptor properties of the host.

An induced-fit process through mechanical pivoting of aromatic walls in host-guest chemistry of calix[6]arene aza-cryptands.

The per-ipso-nitration of a TMPA-capped calix[6]arene has been achieved. The substitution of the six bulky tBu substituents for nitro groups has a strong impact on the behavior of the ligand during guest recognition. The complexation of the aza cap (by H(+) or Cu(+)) associated with the encapsulation of a guest triggers an induced-fit process leading to the loss of the cone conformation of the host in favor of alternate conformations.

Electrochemically driven cup-and-ball CuI and CuII complexes.

The conformation of copper "funnel" complexes that contains a coordinating appended arm can be electrochemically switched between endo, which corresponds to the self-coordination of the arm through the cavity, and exo positions. This process, which is reminiscent of a cup-and-ball device, is activated by an exogenous ligand for complexes that contain a hydroxy-terminated arm. The exchange is electrochemically triggered and is operated in either Cu(I) or Cu(II) redox states, depending on the exogenous ligand, that is, CO or n-butylamine, respectively.

Guest-triggered Zn(II) translocation and supramolecular nuclearity control in calix[6]arene-based complexes.

Two new polytopic ligands based on a calix[6]arene scaffold were synthesized. The truncated cone-shaped calixarene was functionalized at its small rim by a tris-imidazole site, aimed at generating a tetrahedral Zn(II) complex, where a fourth labile site inside the cavity is accessible through the funnel provided by its large rim. Tridentate aza ligands (either two or three) were then grafted at this large rim (the entrance of the cavity).

Guest covalent capture by a host: a biomimetic strategy for the selective functionalization of a cavity.

A biomimetic strategy for the monofunctionalization of a calix[6]arene core is described. It is based on host-guest chemistry (mimicking the Michaelis-Menten adduct in enzymes) and allows the finely tuned pre-organization of the substrate (an alkyne) with respect to the reactant (three azido groups introduced at the calixarene large rim). It is shown that the thermal Huisgen reaction implemented in this work proceeds under very mild conditions with total regioselectivity of the cycloaddition process.

Supramolecular control of hetero-multinuclear polytopic binding of metal ions (Zn(II), Cu(I)) at a single calix[6]arene-based scaffold.

A Calix[6]arene scaffold was functionalized to provide a tridentate binding site at the small rim and three bidentate chelate sites at the large rim of the cone to generate a heteropolytopic ligand. Its complexation to one equivalent of Zn(II) at the small rim yields a funnel complex displaying both host-guest properties and preorganization of the three chelate groups at the large rim. These two aspects allowed the full control of the binding events to regioselectively form dinuclear Zn(II) and heteropolynuclear Zn(II)/Cu(I) complexes.

Synthesis and studies of a water-soluble and air-stable Cu(I)/Cu(II) open-shell funnel complex.

The derivatization of the large rim of a TMPA-capped calix[6]arene (TMPA = tris(2-pyridylmethyl)amine) with three trimethylammonium groups enables the water-solubilization of two air-stable Cu(I)/Cu(II) complexes. These two complexes present a vacant coordination site shielded from the aqueous environment by the calixarene core. The spectroscopic and electrochemical data recorded in pure water indicate that the host-guest properties of the funnel complex are retained in both oxidation states of the copper cation.