David Bardelang

• CNRS at Aix-Marseille University

Despite the development of various controlled release systems for antitumor therapies, off-target side effects remain a persistent challenge. In situ therapeutic synthesis from biocompatible substances offers a safer and more precise alternative. This study presents a hypoxia-initiated supramolecular free radical system capable of inducing intracel...

A series of N‐alkyl‐ and N‐aryl‐viologens has been studied in alkaline solutions. In this work, we evaluated the deuteration rate of the viologens in D2O solutions of pH values ranging from 7.3 to 12.7. Kinetic experiments and computational calculations showed the high reactivity of H−C(2) bonds toward deprotonation of N‐aryl‐pyridinium moieties co...

Now that the chemistry of 1 : 1 host:guest complexes is well‐established, it is surprising to note that higher stoichiometry (oligomeric) complexes, especially those with excess host, remain largely unexplored. Yet, proteins tend to oligomerize, affording new functions for cell machinery. Here, we show that cucurbit[n]uril (CB[n]) macrocycles combi...

Now that the chemistry of 1:1 host:guest complexes is well‐established, it is surprising to note that higher stoichiometry (oligomeric) complexes, especially those with excess host, remain largely unexplored. Yet, proteins tend to oligomerize, affording new functions for cell machinery. Here, we show that cucurbit[n]uril (CB[n]) macrocycles combine...

Previously, we reported a guest molecule containing a viologen (V), a phenylene (P) and an imidazole (I) fragment (VPI) forming a host : guest 2 : 2 complex with cucurbit[8]uril (CB[8]) and an unprecedented 2 : 3 complex with cucurbit[10]uril (CB[10]). To better address the structural features required to form these complexes, two VPI analogues wer...

Ring translocation switches and shuttles featuring a macrocycle (or a ring molecule) navigating between two or more stations continue to attract attention. While the vast majority of these systems are developed in organic solvents, the cucurbituril (CB) macrocycles are ideally suited to prepare such systems in water. Indeed, their stability and the...

Cucurbit[n]uril (CB[n]) macrocycles (especially CB[5] to CB[8]) have shown exceptional attributes since their discovery in 2000. Their stability, water solubility, responsiveness to several stimuli, and remarkable binding properties have enabled a growing number of biological applications. Yet, soon after their discovery, the challenge of their fun...

Here we report the coupling of a cyclic peptide (VH4127) targeting the low density lipoprotein (LDL) receptor (LDLR) noncompetitively to cucurbit[7]uril (CB[7]) to develop a new kind of drug delivery system (DDS), namely, CB[7]-VH4127, with maintained binding affinity to the LDLR. To evaluate the uptake potential of this bismacrocyclic compound, an...

The structure of the Viologen‐Phenylene‐Imidazole (VPI) guest, previously shown to be bound by cucurbit[7]uril (CB[7]) with binding modes depending on pH and silver ions, has been extended by adding hydrophobic groups on the two extremities of VPI before investigations of CB[7] binding by NMR, ITC, X‐ray diffraction, UV‐vis and fluorescence spectro...

Recently, porous organic crystals (POC) based on macrocycles have shown exceptional sorption and separation properties. Yet, the impact of guest presence inside a macrocycle prior to adsorption has not been studied. Here we show that the inclusion of trimethoxybenzyl‐azaphosphatrane in the macrocycle cucurbit[8]uril (CB[8]) affords molecular porous...

recently, porous organic crystals (POC) based on macrocycles have shown exceptional sorption and separation properties. Yet, the impact of guest presence inside a macrocycle prior to adsorption has not been studied. Here we show that the inclusion of trimethoxybenzyl‐azaphosphatrane in the macrocycle cucurbit[8]uril (CB[8]) affords molecular Porous...

The globular and monocationic guest molecule trimethyl‐azaphosphatrane (AZAP, a protonated Verkade superbase) was shown to form a host:guest 1 : 1 complex with the cucurbit[10]uril (CB[10]) macrocycle in water. Molecular dynamics calculations showed that CB[10] adopts an 8‐shape with AZAP occupying the majority of the internal space, CB[10] contrac...

Organic luminescent compounds with high emission properties play a crucial role in fluorescence labelling and optoelectronic devices. In this work, we prepared three water soluble BODIPY derivatives (B-4, B-5, and B-6) which are weakly fluorescent due to non-radiative relaxation pathways (charge transfer: CT or heavy atom effect). However, CB[7] si...

A viologen-phenylene-imidazole (VPI) conjugate, previously shown to be singly complexed by CB[7] and doubly bound by CB[8], is herein shown to form antiparallel triple stacks in water with cucurbit[10]uril (CB[10]), pairwise complexing the guest trimer. The quinary host:guest 2:3 complex showed features assignable to charge-transfer interactions. U...

Molecular machines are ubiquitous in nature and function away from equilibrium by consuming fuels to produce appropriate work. Chemists have recently excelled at mimicking the fantastic job performed by natural molecular machines with synthetic systems soluble in organic solvents. In efforts toward analogous systems working in water, we show that g...

A class of rotaxane is created, not by encapsulating a conventional linear thread, but rather by wrapping a large cucurbit[10]uril macrocycle about a three-dimensional, cylindrical, nanosized, self-assembled supramolecular helicate as the axle. The resulting pseudo-rotaxane is readily converted into a proper interlocked rotaxane by adding branch po...

Poisons always have fascinated humankind. Initially considered as deleterious or hazardous substances, the modern era has witnessed the controlled utilization of dangerous poisons in medicine and cosmetics. Simultaneously, antidotes have become crucial as reversal agents to counteract the effects of a poison, and they are also used today to positiv...

Cucurbiturils can be prime components to build energy ratchets in water. Guest molecules can be exchanged in the synthetic macrocycle cucurbit[7]uril by involving kinetic traps, and in such a way as modulating energy wells and kinetic barriers using pH, light, and redox stimuli Abstract Molecular machines are ubiquitous in nature and function away...

A class of rotaxane is created, not by encapsulating a conventional linear thread, but rather by wrapping a large cucurbit[10]uril macrocycle about a three-dimensional, cylindrical, nanosized, self-assembled supramolecular helicate as the axle. The resulting pseudo-rotaxane is readily converted into a proper interlocked rotaxane by adding branch po...

Macrocycles and related hosts are now being used to reverse the effects of poisonous substances and to alleviate the toxicity of several medicines in vivo. Here, we showcase the emergence of this class of compounds behaving as supramolecular antidotes, some of which outperform ‘gold standards’ in the field.

Proteins are an endless source of inspiration. By carefully tuning the amino‐acid sequence of proteins, nature made them evolve from primary to quaternary structures, a property specific to protein oligomers and often crucial to accomplish their function. On the other hand, the synthetic macrocycles cucurbiturils (CBs) have shown outstanding recogn...

Cucurbit[8]uril can stabilize discrete host:guest n:n oligomers of controlled size and shape in water with properties specific to the oligomers. We collected more than 50 examples and identified several factors explaining the formation of linear or cyclic oligomers and provide some rational to design new assemblies and target advanced properties....

Metal-Organic Framework (MOF) type crystals in which rigid, viologen-based pillars are surrounded by cucurbit[7]uril (CB[7]) macrocycles are described. These Metal-Organic Rotaxane Frameworks (MORF) are obtained by desolvation of a crystal...

A viologen derivative carrying a benzimidazole group (V‐P‐I ²⁺; viologen–phenylene–imidazole V‐P‐I) can be dimerized in water using cucurbit[8]uril (CB[8]) in the form of a 2:2 complex resulting in a negative shift of the guest pKa, by more than 1 pH unit, contrasting with the positive pKa shift usually observed for CB‐based complexes. Whereas 2:2...

The capture of pH‐responsive guest molecules by CB[8] macrocycles made it possible to produce 2:2 host:guest complexes, releasing protons initially trapped on the guests, in a manner similar to the proton release observed in biology and operating through cascade supramolecular events. More information can be found in the Full Paper by R. Wang, A. K...

Triangular shapes have inspired scientists over time and are common in nature, such as the flower petals of oxalis triangularis, or the triangular faces of tetrahedrite crystals or on the icosahedron faces of virus capsids. Supramolecular chemistry has enabled the construction of triangular assemblies, many of which possess functional features. Amo...

A molecular switch built with cucurbit[7]uril and a 3-station viologen-phenylene-imidazole compound exhibited pH actuated ring translocation with high fatigue resistance (up to 100 cycles). The switch movement was harnessed toward...

Among a series of metal ions in water, silver is the only one to remotely and reversibly switch cucurbit[7]uril (CB[7]) movements (translocation or uptake) on a rigid and linear three-station viologen–phenylene–imidazole (V–P–I) derivative, avoiding undesired pH actuation. ¹H NMR, UV–vis spectroscopy, mass spectrometry, ITC, and modeling were combi...

Most 1,4,5,8-naphthalenediimide (NDI) derivatives, especially those with mild π-acidity cannot achieve photoinduced electron-transfer (PET). Here we report our investigations on the binding interactions of a NDI diammonium dichloride salt (NDI•Cl2) with cucurbit[n]uril (CB[n], n = 8, 10) and the formation process of NDI radical anion upon photoexci...

This is the first time that cucurbit[7]uril and cucurbit[8]uril have been demonstrated to serve as synthetic receptors for a halonium guest species, diphenyleneiodonium, modulating its bioactivities and alleviating its cardiotoxicity, which further expands the onium family of guest molecules for cucurbit[n]uril family and provides new insights for...

The interface of nitroxide radicals with cucurbit[n]urils (CB[n]) is covered in this review. Either used as spin probes, spin labels, or stoppers for paramagnetic rotaxanes, nitroxides offer new opportunities to investigate CB[n] and their inclusion complexes, especially thanks to EPR spectroscopy. On the other hand, CB[n] also offer interesting op...

This work describes Latent Fluorescence Particles (LFPs) based on a new environment sensitive carbazole compound aggregated in water, and their use as sensors for probing various cavitands and the different stages of aggregating systems. Cyclodextrins (CDs), cucurbit[n]urils (CB[n], n = 6, 7, 8) and a resorcinarene capsule were used to study the dy...

Small-molecule kinase inhibitors (SMKIs) have been widely used in the treatment of a variety of cancers due to their clinically demonstrated efficacy. However, the use of some SMKIs, such as sorafenib (SO), has been plagued by their cardiotoxicity that has been frequently observed in treated patients. Herein we report that the encapsulation of SO b...

Three new DEPMPO-based spin traps have been designed and synthesized for improved superoxide detection, each carrying a cyclodextrin (CD) moiety but with a different alkyl chain on the phosphorus atom or with a long spacer arm. EPR spectroscopy allowed us to estimate the half-life of the superoxide spin adducts which is close to the value previousl...

Upon supramolecular encapsulation by a synthetic nanocontainer (cucurbit[7]uril), the taste of the Guinness World’s most bitter substance, denatonium benzoate, was dramatically concealed during a two-bottle preference drinking test in a mammalian model, demonstrating the significant potential of cucurbit[7]uril as a taste-masking nanocontainer for...

Fasudil (FSD), a selective rho kinase (ROCK) inhibitor, was found to form 1 : 1 host-guest inclusion complexes with a synthetic macrocyclic receptor, cucurbit[7]uril (CB[7]), in aqueous solutions, as evidenced by (1)H NMR, photoluminescence and UV-visible spectroscopic titrations, isothermal titration calorimetry (ITC) titration, and electrospray i...

Arecoline, as one of the major biologically active compounds extracted from Areca nut, has shown profound links to hepatotoxicity. In this study, the inclusion of arecoline hydrobromide (AH) in a synthetic receptor, cucurbit[7]uril (CB[7]), was demonstrated by 1H NMR spectroscopic titration, isothermal titration calorimetry (ITC), electrospray ioni...

Nitidine chloride (NC) has demonstrated promising anticancer activity. However, NC has also shown non-specific toxicity in various healthy organs such as the liver. In this study, we aimed to develop a supramolecular formulation for NC and investigate the associated benefits of such a supramolecular formulation on modulating its inherent hepatotoxi...

As determined by both 1H NMR and UV-Vis spectroscopic titration, electrospray ionization mass spectrometry (ESI-MS), isothermal titration calorimetry (ITC), and DFT molecular modeling, AGE-breaker alagebrium (ALA) was found to form 1:1 guest-host inclusion complexes with cucurbit[7]uril (CB[7]), with the binding affinity Ka in the order of magnitud...

Cucurbit[7]uril (CB[7]) has recently attracted increasing attention in pharmaceutical sciences due to its great potential in improving the physicochemical properties and bioactivity of drug molecules. Herein, we have investigated the influence of CB[7]'s complexation on the solubility, antimycobacterial activity, and cardiotoxicity of a model anti-...

An ester-type local anesthetic agent, benzocaine (BZC), and its metabolite, para-aminobenzoic acid (PABA), both form 1 : 1 host-guest complexes with cucurbit[7]uril (CB[7]) in aqueous solution and has been observed by 1H NMR, UV-visible spectroscopic titrations (including Job's plot), electrospray ionization (ESI) mass spectrometry, and density fun...

A series of naphthalimide derivatives containing tertiary amine groups (DNNDs) have been prepared. Some of these derivatives (e.g. DNND3, DNND4 and DNND5) exhibit interesting shifted absorption so that they can be utilized as versatile photoinitiators upon exposure to various violet and blue LEDs (385, 405, 455 and 470 nm). They are particularly ef...

Cucurbit[7]uril (CB[7]) was found in vitro to sequester the neurotoxins MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and MPP+ (N-methyl-4-phenylpyridine). The CB[7]/neurotoxin host-guest complexes were studied in detail with 1H NMR, electrospray ionization mass spectrometry, UV-visible spectroscopic titration, and molecular modeling by densi...

Nitroxide free radicals have been used to study the inner space of one of Rebek’s water-soluble capsules. EPR and 1H NMR spectroscopy, ESI-MS, and DFT calculations showed a preference for the formation of 1:2 complexes. EPR titrations allowed us to determine binding constants (Ka) in the order of 107 M−2. EPR spectral-shape analysis provided inform...

We describe a photochemical method to introduce a single alcohol function directly on cucurbit[n]urils (n = 5, 6, 7, 8) with conversions of the order 95-100% using hydrogen peroxide and UV light. The reaction was easily scaled up to 1 gram for CB[6] and CB[7]. Spin trapping of cucurbituril radicals combined with MS experiments allowed us to get ins...

The (15-oxo-3,7,11-triazadispiro[5.1.5.3]hexadec-7-yl) oxidanyl), a bis-spiropiperidinium nitroxide derived from TEMPONE can be included in cucurbit[7]uril to form a strong (Ka ~ 2. 10 5 M-1) CB[7]@bPTO complex. EPR and MS spectra, DFT calculations, and unparalleled increased resistance (~ factor 10 3) toward ascorbic acid reduction, show evidence...

Seven naphthalimide derivatives (NDP1-NDP7) with different substituents have been designed as versatile photoinitiators (PIs), and some of them when combined with an iodonium salt (and optionally N-vinylcarbazole) or an amine (and optionally chlorotriazine) are expected to exhibit an enhanced efficiency to initiate the cationic polymerization of ep...

The macrocyclic molecular container cucurbit[7]uril (CB[7]), the most water-soluble homologue in the cucurbit[n]uril family (n = 5–8, 10, 14), has been evaluated for its in vivo toxicity profile, including its developmental toxicity such as its effect on hatching, growth and survival, as well as its potential organ-specific toxicities such as cardi...

A dinitroxide biradical (dCdO) has the peculiar tendency to crystallize in non-centrosymmetric polar space groups either as a stable dichloromethane solvate or as a pure phase. The molecules arrange with no compensation of their dipolar moment resulting in net macroscopic polar order.

The (15-oxo-3,7,11-triazadispiro[5.1.5.3]hexadec-7-yl)oxidanyl, a bis-spiropiperidinium nitroxide derived from TEMPONE, can be included in cucurbit[7]uril to form a strong (Ka ∼ 2 × 105 M−1) CB[7]@bPTO complex. EPR and MS spectra, DFT calculations, and unparalleled increased resistance (a factor of ∼103) toward ascorbic acid reduction show evidence...

The flexible tetranitroxide 4T has been prepared and was shown to exhibit a nine line EPR spectrum in water, characteristic of significant through space spin exchange (Jij) between four electron spins interacting with four nitrogen nuclei (Jij > aN). Addition of CB[8] to 4T decreases dramatically all the Jij couplings and the nine line spectrum is...

Solid state 13C NMR spectra of several cucurbituril materials, CB[n] where n = 5, 6, 7 and 8, have been analysed in detail. Where crystal structures are known the complex splitting patterns for the CO, CH and CH2 resonances can be directly related to the different site symmetries imposed on the CB molecule by the crystal. Conversely, where the stru...

The dinitroxide bis(TEMPO) bisketal (bTbk) was shown to crystallize into open frameworks whose structures were determined by single-crystal X-ray diffraction. We show that bTbk can be used as a supramolecular building block for the hosting of a plethora of guests inside the 1D channels of its paramagnetic framework, including other radicals such as...

The dinitroxide biradical crystallizes forming hexagonal open frameworks with one-dimensional corrugated channels filled with crystallization solvent. The large pockets constitutive of the channels allowed the inclusion of C60 in the paramagnetic network. The rapidity and high fidelity of crystal growth were used to prepare isostructural multilayer...

Toluene and 1-chloronaphthalene immobilization was observed when perturbing stimuli such as agitation or ultrasound are applied during the cooling of a hot supersaturated solution of the rigid dinitroxide bTbk. X-Ray diffraction and cryo-SEM on gels and solid samples (crystal, powder) confirmed the pivotal role of clathrate type microcrystals in th...

The electron paramagnetic resonance (EPR) parameters of a free radical depend strongly on its microenvironment and stable radicals can be used as reporter molecules for the EPR probing of various chemical and biological systems. Nowadays, nitroxides and trityl radicals are the most important spin labels or spin probes and their use in various appli...

Anchoring of a self-assembling dipeptide on the surface of core/shell CdSe/ZnS quantum dots resulted in a competition between coordination of the surface atoms of the QDs and the strong tendency for the dipeptide to self-assemble in toluene. This resulted in a mild QD etching and in a corresponding increase in the band gap of the nanocrystals whose...

Cucurbit[n]urils (CB[n], n = 5–8) have been prepared, separated, and purified, and the structure of their solid state assemblies has been addressed. A number of general features were identified which are of interest to understand some peculiar properties of cucurbiturils (solubility, aggregation, assembly, transformation to porous crystals, influen...

The layered assembly of fluorescent CdSe/ZnS quantum dots (QDs) on the surface of p-tert-butylcalix[8]arene microcrystals is reported.

In a recent paper (Bardelang et al. in J Org Chem 71:7657–7667, 2006), the deep inclusion of the TIPNO (1-phenyl-2-methylpropyl-1,1-dimethylethyl-2-nitroxide) free radical attached to a permethylated β-cyclodextrin (TRIMEB) into its cavity was questioned. In the present paper it is shown that the results of X-band and W-band electron paramagnetic r...

The preparation of entrapped CdSe?ZnS fluorescent quantum dots (QDs) in cucurbituril (CB) polymer capsules is reported.

A study was conducted to demonstrate the preparation and EPR investigation of a new DEPMPO-appended β-cyclodextrin derivative CD-DEPMPO and its performance regarding the superoxide detection in biological system models. CD-DEPMPO was prepared in a one-step sequence with high yield by reacting NHS-DEPMPO binding block with 6-monodeoxy-6-monoamino pe...

Coumarin was found to form stable inclusion complexes with cucurbiturils. In the presence of cucurbit[7]uril (CB[7]), 1 : 1 inclusion complexes were observed in aqueous solution, as monitored by (1)H NMR and UV-visible absorption spectroscopies, and further supported by ab initio calculations, whereas with cucurbit[8]uril (CB[8]) a solid phase 1 :...

Ultrasound is progressively being recognized as a new powerful tool for the surprising yet effective gelation of organic liquids and water by supramolecular gelators, the diversity of which is discussed in this Highlight article, as well as the key concepts of sonocrystallization and mismatched intra-/intermolecular interactions, driving self-assem...

Nitroxide free radicals are demonstrated to be useful guests for probing cucurbit[n]uril (CB[n]) assemblies in water by EPR spectroscopy. CB[7] and CB[8] significantly aggregate either in solution or in the solid state (as evidenced by a single-crystal X-ray structure in which CB[8] forms supramolecular triangles with 4-methoxy-TEMPO). The included...

The preparation of quantum dots (QD)-dipeptide nanocomposite gels with high luminescence under UV light, has been demonstrated. The resultant products can be changed from liquid to solid by ultrasound and changed back into liquid after heating. Hexane suspensions of CdSe/ZnS QDs covered with trioctylphosphine oxide (TOPO) as surface ligands were us...

Cucurbit[5]uril hydrochloride hydrate crystals with large water-filled channels transform to a highly stable layer structure via a single-crystal to single-crystal mechanism; (129)Xe NMR showed that porosity in CB[5] samples depends critically on the method of preparation.

Abstract: A readily synthesized dipeptide shows unprecedented gelation behavior when dispersed and submitted to ultrasound in nonsolvents. SEM and FFEM revealed spectacular shape changes from a sheet-like material into a highly interconnected fiber network and ribbons while the dipeptide maintains an anti conformation inside -sheets at the molecula...

Gelators, compounds able to solidify solvents, and in particular hydrogelators are interesting soft materials. In this paper we have synthesized cyclotriveratrylene (CTV) platforms symmetrically end-substituted with pendent primary amines or nicotamic substituents. These non-amphiphilic structures induce self-assembly in a large variety of solvents...

Metal-free cucurbit[6]uril and cucurbit[8]uril hydrate crystals present water-filled channels consisting of perfectly aligned one-dimensional macrocycle nanotubes.

A new metallo-organic gelator formed from an admixture of a substituted nicotinic acid and its sodium salt is described. The nicotinic acid is substituted in the 6-position by an acetal functionality. The crystal structure of the 1:1 mixture revealed that the sodium atoms are aligned in infinite chains with the two organic units hydrogen bonded tog...

alpha-Phenyl-N-tert-butylnitrone (PBN) derivatives bound to beta-cyclodextrin derivatives have been synthesized. Inclusion of the PBN group into the beta-cyclodextrin moiety is host- and temperature-dependent. In the case of the nitrone linked to permethylated cyclodextrin (Me3CD-PBN), the thermokinetic parameters are in favour of a slow chemical e...

236CDTIPNO, a derivative of the persistent free radical TIPNO (1,1-dimethylethyl 2-methyl-1-phenylpropyl nitroxide) covalently bound to a permethylated-beta-cyclodextrin, was prepared. Self-association of 236CDTIPNO in water was proved by solvent- and competition-dependent EPR spectroscopy experiments with 2,6-di-O-Me-beta-cyclodextrin (DIMEB) and...

The free radical trapping properties of eight 5-alkoxycarbonyl-5-methyl-1-pyrroline N-oxide (EMPO) type nitrones and those of 5,5-dimethyl-1-pyrroline N-oxide (DMPO) were evaluated for trapping of superoxide anion radicals in the presence of 2,6-di-O-methyl-beta-cyclodextrin (DM-beta-CD). (1)H-NMR titrations were performed to determine both stoichi...

(1)H NMR and electron paramagnetic resonance (EPR) titrations were used to determine the association constants of the complexes of alpha-phenyl-N-tert-butylnitrone (PBN) analogues and their superoxide spin adducts, respectively, with methylated beta-cyclodextrins. A 1:1 stoichiometry for the nitrones with randomly methylated beta-cyclodextrin and 2...

Recently, cyclodextrin derivatives were reported to increase significantly the half-life of the spin adducts resulting from the trapping of free radicals with nitrones. To address the physicochemical characteristics of these complexes, a series of α-phenyl-N-tert-butylnitrone (PBN) analogues containing hydroxy groups on the tert-butyl group was pre...

Export Date: 12 June 2012, Source: Scopus