Pentafluorophenyl Esters as Exchangeable Stoppers for the Construction of Photoactive [2]Rotaxanes.

Stable pillar[5]arene-containing [2]rotaxane building blocks with pentafluorophenyl ester stoppers have been efficiently prepared on a multi-gram scale. Reaction of these building blocks with various nucleophiles gave access to a wide range of [2]rotaxanes with amide, ester or thioester stoppers in good to excellent yields. The rotaxane structure is fully preserved during these chemical transformations. Actually, the addition-elimination mechanism at work during these transformations totally prevents the unthreading of the axle moiety of the mechanically interlocked system. The stopper exchange reactions were optimized both in solution and under mechanochemical solvent-free conditions. While amide formation is more efficient in solution, the solvent-free conditions are more powerful for the transesterification reactions. Starting from a fullerene-functionalized pillar[5]arene derivative, this new strategy gave easy access to a photoactive [2]rotaxane incorporating a C60 moiety and two Bodipy stoppers. Despite the absence of covalent connectivity between the Bodipy and the fullerene moieties in this photoactive molecular device, efficient through-space excited state interactions have been evidenced in this rotaxane.

Grafting Dendrons onto Pillar[5]Arene Scaffolds.

With their ten peripheral substituents, pillar[5]arenes are attractive compact scaffolds for the construction of nanomaterials with a controlled number of functional groups distributed around the macrocyclic core. This review paper is focused on the functionalization of pillar[5]arene derivatives with small dendrons to generate dendrimer-like nanomaterials and bioactive compounds. Examples include non-viral gene vectors, bioactive glycoclusters, and liquid-crystalline materials.

Topological and Steric Constraints to Stabilize Heteroleptic Copper(I) Complexes Combining Phenanthroline Ligands and Phosphines.

Heteroleptic copper(I) complexes combining phenanthroline derivatives (NN) and chelating bisphosphine ligands (PP) are an important class of luminescent materials for various applications. Although thermodynamically stable, [Cu(NN)(PP)]+ derivatives are also kinetically unstable. As a result, a dynamic ligand-exchange reaction is often observed in solution, leading to a dynamic mixture of heteroleptic and homoleptic complexes. To prevent the formation of the homoleptic species, macrocyclic phenanthroline ligands have been used for the preparation of [Cu(NN)(PP)]+ pseudorotaxanes. The topological constraint resulting from the macrocyclic structure of the NN ligand drives the thermodynamic equilibrium towards the exclusive formation of the heteroleptic complex as long as the macrocycle is large and flexible enough to allow for the threading of the PP ligand. Conversely, when the threading is prevented by steric constraints, unprecedented copper(I) complexes with a trigonal coordination geometry are obtained. These results are summarized in the present concept article.

Heteroleptic Copper(I) Complexes Prepared from Phenanthroline and Bis-Phosphine Ligands: Rationalization of the Photophysical and Electrochemical Properties.

The electronic and structural properties of ten heteroleptic [Cu(NN)(PP)]+ complexes have been investigated. NN indicates 1,10-phenanthroline (phen) or 4,7-diphenyl-1,10-phenanthroline (Bphen); each of these ligands is combined with five PP bis-phosphine chelators, i.e., bis(diphenylphosphino)methane (dppm), 1,2-bis(diphenylphosphino)ethane (dppe), 1,3-bis(diphenylphosphino)propane (dppp), 1,2-bis(diphenylphosphino)benzene (dppb), and bis[(2-diphenylphosphino)phenyl] ether (POP). All complexes are mononuclear, apart from those based on dppm, which are dinuclear. Experimental data-also taken from the literature and including electrochemical properties, X-ray crystal structures, UV-vis absorption spectra in CH2Cl2, luminescence spectra and lifetimes in solution, in PMMA, and as powders-have been rationalized with the support of density functional theory calculations. Temperature dependent studies (78-358 K) have been performed for selected complexes to assess thermally activated delayed fluorescence. The main findings are (i) dependence of the ground-state geometry on the crystallization conditions, with the same complex often yielding different crystal structures; (ii) simple model compounds with imposed C2 v symmetry ([Cu(phen)(PX3)2]+; X = H or CH3) are capable of modeling structural parameters as a function of the P-Cu-P bite angle, which plays a key role in dictating the overall structure of [Cu(NN)(PP)]+ complexes; (iii) as the P-Cu-P angle increases, the energy of the metal-to-ligand charge transfer absorption bands linearly increases; (iv) the former correlation does not hold for emission spectra, which are red-shifted for the weaker luminophores; (v) the larger the number of intramolecular π-interactions within the complex in the ground state, the higher the luminescence quantum yield, underpinning a geometry locking effect that limits the structural flattening of the excited state. This work provides a general framework to rationalize the structure-property relationships of [Cu(NN)(PP)]+, a class of compounds of increasing relevance for electroluminescent devices, photoredox catalysis, and solar-to-fuels conversion, which so far have been investigated in an unsystematic fashion, eluding a comprehensive understanding.

Heteroleptic Copper(I) Pseudorotaxanes Incorporating Macrocyclic Phenanthroline Ligands of Different Sizes.

A series of copper(I) pseudorotaxanes has been prepared from bis[2-(diphenylphosphino)phenyl] ether (POP) and macrocyclic phenanthroline ligands with different ring sizes (m30, m37, and m42). Variable-temperature studies carried out on the resulting [Cu(mXX)(POP)]+ (mXX = m30, m37, and m42) derivatives have revealed a dynamic conformational equilibrium due to the folding of the macrocyclic ligand. The absorption and luminescence properties of the pseudorotaxanes have been investigated in CH2Cl2. They exhibit metal-to-ligand charge-transfer emission with photoluminescence quantum yields (PLQYs) in the range 20-30%. The smallest system [Cu(m30)(POP)]+ shows minimal differences in spectral shape and position compared to its analogues, suggesting a slightly distorted coordination environment. PLQY is substantially enhanced in poly(methyl methacrylate) films (∼40-45%). The study of emission spectra and excited-state lifetimes in powder samples as a function of temperature (78-338 K) reveals thermally activated delayed fluorescence, with sizable differences in the singlet-triplet energy gap compared to the reference compound [Cu(dmp)(POP)]+ (dmp = 2,9-dimethyl-1,10-phenanthroline) and within the pseudorotaxane series. The system with the largest ring ([Cu(m42)(POP)]+) has been tested as emissive material in OLEDs and affords bright green devices with higher luminance and greater stability compared to [Cu(dmp)(POP)]+, which lacks the macrocyclic ring. This highlights the importance of structural factors in the stability of electroluminescent devices based on Cu(I) materials.

Giant Glycosidase Inhibitors: First- and Second-Generation Fullerodendrimers with a Dense Iminosugar Shell.

The multivalent effect in glycosidase inhibition is a new topic in glycoscience that has emerged a few years ago, with the discovery of neoglycoclusters displaying strong binding enhancements over the corresponding monovalent inhibitor. Iminosugar-fullerene conjugates with high valencies have been prepared from iminosugar-terminated dendrons and a clickable fullerene hexa-adduct scaffold. The simultaneous grafting of twelve dendrons allows for a very fast dendritic growth thus limiting the number of synthetic steps required to prepare compounds with a high number of peripheral units. The grafting of first- and second-generation dendrons provided fullerodendrimers surrounded by 36 and 108 peripheral iminosugars, respectively. Inhibition studies have been carried out with a panel of glycosidases. In the particular case of Jack bean α-mannosidase, the 108-valent nanoconstruct displays inhibition in the nanomolar range and an additional binding enhancement of one order of magnitude when compared to the 36-valent analogues.

Preparation of Pillar[5]arene-Based [2]Rotaxanes by a Stopper-Exchange Strategy.

A pillar[5]arene-containing rotaxane building block bearing exchangeable stoppers has been prepared in multigram scale quantities with high yields from the reaction of 2,4-dinitrophenol (DNP) with the inclusion complex resulting from the association of dodecanedioyl chloride with 1,4-diethoxypillar[5]arene. Stopper exchange reactions have been achieved by treatment of the resulting DNP diester with various amines through an addition-elimination mechanism preventing the unthreading of the axle component during the reaction and thus preserving the [2]rotaxane structures. The resulting diamide [2]rotaxane derivatives have thus been obtained in good to excellent yields. Importantly, [2]rotaxanes difficult or impossible to prepare by direct introduction of the two stoppers in a single synthetic step are now easily available.

A Rotaxane Scaffold for the Construction of Multiporphyrinic Light-Harvesting Devices.

A sophisticated photoactive molecular device has been prepared by combining recent concepts for the preparation of multifunctional nanomolecules (click chemistry on multifunctional scaffolds) with supramolecular chemistry (self-assembly to prepare rotaxanes). Specifically, a clickable [2]rotaxane scaffold incorporating a free-base porphyrin stopper has been prepared and functionalized with ten peripheral Zn(II)-porphyrin moieties. Electrochemical investigations of the final compound revealed a peculiar behavior resulting from the intramolecular coordination of the Zn(II) porphyrin moieties to 1,2,3-triazole units. Finally, steady state investigations of the compound combining Zn(II) and free-base porphyrin moieties have shown that this compound is a light-harvesting device capable of channeling the light energy from the peripheral Zn(II)-porphyrin subunits to the core by singlet-singlet energy transfer.

Coordination-Driven Folding in Multi-ZnII -Porphyrin Arrays Constructed on a Pillar[5]arene Scaffold.

Pillar[5]arene derivatives bearing peripheral porphyrin subunits have been efficiently prepared from a deca-azide pillar[5]arene building block (17) and ZnII -porphyrin derivatives bearing a terminal alkyne function (9 and 16). For the resulting deca-ZnII -porphyrin arrays (18 and 20), variable temperature NMR studies revealed an intramolecular complexation of the peripheral ZnII -porphyrin moieties by 1,2,3-triazole subunits. As a result, the molecules adopt a folded conformation. This was further confirmed by UV/Vis spectroscopy and cyclic voltammetry. In addition, we have also demonstrated that the coordination-driven unfolding of 18 and 20 can be controlled by an external chemical stimulus. Specifically, addition of an imidazole derivative (22) to solution of 18 or 20 breaks the intramolecular coordination at the origin of the folding. The resulting molecular motions triggered by the addition of the imidazole ligand mimic the blooming of a flower.

Construction of giant glycosidase inhibitors from iminosugar-substituted fullerene macromonomers.

An ultra-fast synthetic procedure based on grafting of twelve fullerene macromonomers onto a fullerene hexa-adduct core was used for the preparation of a giant molecule with 120 peripheral iminosugar residues. The inhibition profile of this giant iminosugar ball was evaluated against various glycosidases. In the particular case of the Jack bean α-mannosidase, a dramatic enhancement of the glycosidase inhibitory effect was observed for the giant molecule with 120 peripheral subunits as compared to that of the corresponding mono- and dodecavalent model compounds.

Synthesis of giant globular multivalent glycofullerenes as potent inhibitors in a model of Ebola virus infection.

The use of multivalent carbohydrate compounds to block cell-surface lectin receptors is a promising strategy to inhibit the entry of pathogens into cells and could lead to the discovery of novel antiviral agents. One of the main problems with this approach, however, is that it is difficult to make compounds of an adequate size and multivalency to mimic natural systems such as viruses. Hexakis adducts of [60]fullerene are useful building blocks in this regard because they maintain a globular shape at the same time as allowing control over the size and multivalency. Here we report water-soluble tridecafullerenes decorated with 120 peripheral carbohydrate subunits, so-called 'superballs', that can be synthesized efficiently from hexakis adducts of [60]fullerene in one step by using copper-catalysed azide­alkyne cycloaddition click chemistry. Infection assays show that these superballs are potent inhibitors of cell infection by an artificial Ebola virus with half-maximum inhibitory concentrations in the subnanomolar range.

Piling Up Pillar[5]arenes To Self-Assemble Nanotubes.

New liquid-crystalline pillar[5]arene derivatives have been prepared by grafting first-generation Percec-type poly(benzylether) dendrons onto the macrocyclic scaffold. The molecules adopt a disc-shaped structure perfectly suited for self-organization into a columnar liquid-crystalline phase. In this way, the pillar[5]arene cores are piled up, thus forming a nanotubular wire encased within a shell of peripheral dendrons. The capability of pillar[5]arenes to form inclusion complexes has been also exploited. Specifically, detailed binding studies have been carried out in solution with 1,6-dicyanohexane as the guest. Inclusion complexes have also been prepared in the solid state. Supramolecular organization into the Colh mesophase has been deduced from X-ray diffraction data and found to be similar to that observed within the crystal lattice of a model inclusion complex prepared from 1,4-dimethoxypillar[5]arene and 1,6-dicyanohexane.

Pillar[5]arene-Based Glycoclusters: Synthesis and Multivalent Binding to Pathogenic Bacterial Lectins.

The synthesis of pillar[5]arene-based glycoclusters has been readily achieved by CuAAC conjugations of azido- and alkyne-functionalized precursors. The lectin binding properties of the resulting glycosylated multivalent ligands have been studied by at least two complementary techniques to provide a good understanding. Three lectins were selected from bacterial pathogens based on their potential therapeutic applications as anti-adhesives, namely LecA and LecB from Pseudomonas aeruginosa and BambL from Burkholderia ambifaria. As a general trend, multivalency improved the binding to lectins and a higher affinity can be obtained by increasing to a certain limit the length of the spacer arm between the carbohydrate subunits and the central macrocyclic core.

Fucofullerenes as tight ligands of RSL and LecB, two bacterial lectins.

A series of water-soluble glycofullerenes containing up to 24 fucose residues have been prepared. These compounds were tested against the two bacterial fucose-binding lectins LecB and RSL, and C60(E)12 bearing 24 fucose residues appeared to be the best known inhibitor of both lectins to date. We have shown that increasing both the valency and the length of the spacer between the central core and the peripheral sugars can be beneficial for the affinity.

Langmuir and Langmuir-Blodgett Films from Amphiphilic Pillar[5]arene-Containing [2]Rotaxanes.

Amphiphilic pillar[5]arene-containing [2]rotaxanes have been prepared and fully characterized. In the particular case of the [2]rotaxane incorporating a 1,4-diethoxypillar[5]arene subunit, the structure of the compound was confirmed by X-ray crystal structure analysis. Owing to a good hydrophilic/hydrophobic balance, stable Langmuir films have been obtained for these rotaxanes and the size of the peripheral alkyl chains on the pillar[5]arene subunit has a dramatic influence on the reversibility during compression-decompression cycles. Indeed, when these are small enough, molecular reorganization of the rotaxane by gliding motions are capable of preventing strong π-π interactions between neighboring macrocycles in the thin film.

Self-organisation of dodeca-dendronized fullerene into supramolecular discs and helical columns containing a nanowire-like core.

Twelve chiral and achiral self-assembling dendrons have been grafted onto a [60]fullerene hexa-adduct core by copper-catalyzed alkyne azide "click" cycloaddition. The structure adopted by these compounds was determined by the self-assembling peripheral dendrons. These twelve dendrons mediate the self-organisation of the dendronized [60]fullerene into a disc-shaped structure containing the [60]fullerene in the centre. The fullerene-containing discs self-organise into helical supramolecular columns with a fullerene nanowire-like core, forming a 2D columnar hexagonal periodic array. These unprecedented supramolecular structures and their assemblies are expected to provide new developments in chiral complex molecular systems and their application to organic electronics and solar cells.

Combining topological and steric constraints for the preparation of heteroleptic copper(I) complexes.

Heteroleptic copper(I) complexes have been prepared from a macrocyclic ligand incorporating a 2,9-diphenyl-1,10-phenanthroline subunit (M30) and two bis-phosphines, namely bis[(2-diphenylphosphino)phenyl] ether (POP) and 1,3-bis(diphenylphosphino)propane (dppp). In both cases, the diphenylphosphino moieties of the PP ligand are too bulky to pass through the 30-membered ring of M30 during the coordination process, hence the formation of C2v-symmetrical pseudo-rotaxanes is prevented. When POP is used, X-ray crystal structure analysis shows the formation of a highly distorted [Cu(M30)(POP)](+) complex in which the POP ligand is only partially threaded through the M30 unit. This compound is poorly stable as the Cu(I) cation is not in a favorable coordination environment due to steric constraints. By contrast, in the case of dppp, the bis-phosphine ligand undergoes both steric and topological constraints and adopts a nonchelating coordination mode to generate [Cu2(M30)2(µ-dppp)](BF4)2. This compound exhibits metal-to-ligand charge transfer (MLCT) emission characterized by a very large Stokes' shift (≈200 nm) that is not attributed to a dramatic structural distortion between the ground and the emitting states but to very weak MLCT absorption transitions at longer wavelengths. Accordingly, [Cu2(M30)2(µ-dppp)](BF4)2 shows unusually high luminescence quantum yields for Cu(I) complexes, both in solution and in the solid state (0.5 and 7 %, respectively).

Polycationic pillar[5]arene derivatives: interaction with DNA and biological applications.

Dendritic pillar[5]arene derivatives have been efficiently prepared by grafting dendrons with peripheral Boc-protected amine subunits onto a preconstructed pillar[5]arene scaffold. Upon cleavage of the Boc-protected groups, water-soluble pillar[5]arene derivatives with 20 (13) and 40 (14) peripheral ammonium groups have been obtained. The capability of these compounds to form stable nanoparticles with plasmid DNA has been demonstrated by gel electrophoresis, transmission electron microscopy (TEM), and dynamic light scattering (DLS) investigations. Transfection efficiencies of the self-assembled 13/pCMV-Luc and 14/pCMV-Luc polyplexes have been evaluated in vitro with HeLa cells. The transfection efficiencies found for both compounds are good, and pillar[5]arenes 13 and 14 show very low toxicity if any.

Heteroleptic copper(I) complexes prepared from phenanthroline and bis-phosphine ligands.

Preparation of [Cu(NN)(PP)](+) derivatives has been systematically investigated starting from two libraries of phenanthroline (NN) derivatives and bis-phosphine (PP) ligands, namely, (A) 1,10-phenanthroline (phen), neocuproine (2,9-dimethyl-1,10-phenanthroline, dmp), bathophenanthroline (4,7-diphenyl-1,10-phenanthroline, Bphen), 2,9-diphenethyl-1,10-phenanthroline (dpep), and 2,9-diphenyl-1,10-phenanthroline (dpp); (B) bis(diphenylphosphino)methane (dppm), 1,2-bis(diphenylphosphino)ethane (dppe), 1,3-bis(diphenylphosphino)propane (dppp), 1,2-bis(diphenylphosphino)benzene (dppb), 1,1'-bis(diphenylphosphino)ferrocene (dppFc), and bis[(2-diphenylphosphino)phenyl] ether (POP). Whatever the bis-phosphine ligand, stable heteroleptic [Cu(NN)(PP)](+) complexes are obtained from the 2,9-unsubstituted-1,10-phenanthroline ligands (phen and Bphen). By contrast, heteroleptic complexes obtained from dmp and dpep are stable in the solid state, but a dynamic ligand exchange reaction is systematically observed in solution, and the homoleptic/heteroleptic ratio is highly dependent on the bis-phosphine ligand. Detailed analysis revealed that the dynamic equilibrium resulting from ligand exchange reactions is mainly influenced by the relative thermodynamic stability of the different possible complexes. Finally, in the case of dpp, only homoleptic complexes were obtained whatever the bis-phosphine ligand. Obviously, steric effects resulting from the presence of the bulky phenyl rings on the dpp ligand destabilize the heteroleptic [Cu(NN)(PP)](+) complexes. In addition to the remarkable thermodynamic stability of [Cu(dpp)2]BF4, this negative steric effect drives the dynamic complexation scenario toward almost exclusive formation of homoleptic [Cu(NN)2](+) and [Cu(PP)2](+) complexes. This work provides the definitive rationalization of the stability of [Cu(NN)(PP)](+) complexes, marking the way for future developments in this field.

Synthesis of optically pure [60]fullerene e,e,e-tris adducts.

The reaction of readily available optically active Si-tethered tris(malonates) with C60 gave easily separable diastereoisomers differing by the absolute configuration of the inherently chiral addition pattern on the fullerene core. The absolute configuration of the e,e,e addition pattern has been unambiguously determined using X-ray crystal structure analysis.