Franck Meyer

Research in Drug Development (RD3)

Microbiology, Bioorganic and Macromolecular Chemistry

His research activities

His interests are focused on the applications of halogen bonding in materials science and crystal engineering, and the preparation of biocompatible/biodegradable polymers targeting drug delivery systems.

Top ten recent articles

Articles dans des revues avec comité de lecture

2023

Insight into Unusual Supramolecular Self-Assemblies of Terthiophenes Directed by Weak Hydrogen Bonding

A supramolecular self-assembly of semiconducting polymers and small molecules plays an important role in charge transportation, performance, and lifetime of an optoelectronic device. Tremendous efforts have been put into the strategies to self-organize these materials. In this regard, here, we present the self-organization of terthiophene and its methyl alcohol derivative with 4,4′-bipyridine (44BiPy). An unexpected 2D layered organization of 5,5″-dimethyl-2,2′:5′,2″-terthiophene (DM3T) and 44BiPy was obtained and analyzed. Single-crystal X-ray diffraction analysis revealed that DM3T and 44BiPy consist of stacked, almost independent, infinite 2D layers while held together by weak hydrogen bonds. In addition to this peculiar supramolecular arrangement of these compounds, the investigation of their photophysical properties showed strong fluorescence quenching of DM3T by 44BiPy in the solid state, suggesting an efficient charge transfer. On the other hand, the methyl alcohol derivative of terthiophene, DM3TMeOH, organized in a closed cyclic motif with 44BiPy via hydrogen bonds.

Easy, Flexible and Standardizable Anti-Nascent Biofilm Activity Assay to Assess Implant Materials

Medical implants have improved the quality of life of many patients. However, surgical intervention may eventually lead to implant microbial contamination. The aims of this research were to develop an easy, robust, quantitative assay to assess surface antimicrobial activities, especially the anti-nascent biofilm activity, and to identify control surfaces, allowing for international comparisons. Using new antimicrobial assays to assess the inhibition of nascent biofilm during persistent contact or after transient contact with bacteria, we show that the 5 cent Euro coin or other metal-based antibacterial coins can be used as positive controls, as more than 4 log reduction on bacterial survival was observed when using either S. aureus or P. aeruginosa as targets. The methods and controls described here could be useful to develop an easy, flexible and standardizable assay to assess relevant antimicrobial activities of new implant materials developed by industries and academics.

Halogen-Bonded Thiophene Derivatives Prepared by Solution and/or Mechanochemical Synthesis. Evidence of N···S Chalcogen Bonds in Homo- and Cocrystals

Synthesis and biological activity of iron(II), iron(III), nickel(II), copper(II) and zinc(II) complexes of aliphatic hydroxamic acids

2022

Design of Thermoplastic Polyurethanes with Conferred Antibacterial, Mechanical, and Cytotoxic Properties for Catheter Application

Self-assembled ruthenium and osmium nanosystems display a potent anticancer profile by interfering with metabolic activity

We disclose novel amphiphilic ruthenium and osmium complexes that auto-assemble into nanomedicines with potent antiproliferative activity by inhibition of mitochondrial respiration. The self-assembling units were rationally designed from the [M(p-cymene)(1,10-phenanthroline)Cl]PF6 motif (where M is either RuII or OsII) with an appended C16 fatty chain to achieve high cellular activity, nano-assembling and mitochondrial targeting. These amphiphilic complexes block cell proliferation at the sub-micromolar range and are particularly potent towards glioblastoma neurospheres made from patient-derived cancer stem cells. A subcutaneous mouse model using these glioblastoma stem cells highlights one of our C16 OsII nanomedicines as highly successful in vivo. Mechanistically, we show that they act as metabolic poisons, strongly impairing mitochondrial respiration, corroborated by morphological changes and damage to the mitochondria. A genetic strategy based on RNAi gave further insight on the potential involvement of microtubules as part of the induced cell death. In parallel, we examined the structural properties of these new amphiphilic metal-based constructs, their reactivity and mechanism.

Pyrrovobasine, hybrid alkylated pyrraline monoterpene indole alkaloid pseudodimer discovered using a combination of mass spectral and NMR-based machine learning annotations

The MS 2 -guided phytochemical investigation of Voacanga africana stem bark resulted in the isolation of pyrrovobasine, the first pyrraline-containing MIA.

Thermoplastic polyurethanes for biomedical application: A synthetic, mechanical, antibacterial, and cytotoxic study

2021

Stimuli Responsive Materials Supported by Orthogonal Hydrogen and Halogen Bonding or I···Alkene Interaction

Smart materials represent an elegant class of (macro)-molecules endowed with the ability to react to chemical/physical changes in the environment. Herein, we prepared new photo responsive azobenzenes possessing halogen bond donor groups. The X-ray structures of two molecules highlight supramolecular organizations governed by unusual noncovalent bonds. In azo dye I-azo-NO2, the nitro group is engaged in orthogonal H···O···I halogen and hydrogen bonding, linking the units in parallel undulating chains. As far as compound I-azo-NH-MMA is concerned, a non-centrosymmetric pattern is formed due to a very rare I···π interaction involving the alkene group supplemented by hydrogen bonds. The Cambridge Structural Database contains only four structures showing the same I···CH2=C contact. For all compounds, an 19F-NMR spectroscopic analysis confirms the formation of halogen bonds in solution through a recognition process with chloride anion, and the reversible photo-responsiveness is demonstrated upon exposing a solution to UV light irradiation. Finally, the intermediate I-azo-NH2 also shows a pronounced color change due to pH variation. These azobenzenes are thereby attractive building blocks to design future multi-stimuli responsive materials for highly functional devices.

Voatriafricanines A and B, Trimeric Vobasine-Aspidosperma-Aspidosperma Alkaloids from Voacanga africana

Synthesis, structure and anticancer properties of new biotin- and morpholine-functionalized ruthenium and osmium half-sandwich complexes.

Ruthenium (Ru) and osmium (Os) complexes are of sustained interest in cancer research and may be alternative to platinum-based therapy. We detail here three new series of ruthenium and osmium complexes, supported by physico-chemical characterizations, including time-dependent density functional theory, a combined experimental and computational study on the aquation reactions and the nature of the metal-arene bond. Cytotoxic profiles were then evaluated on several cancer cell lines although with limited success. Further investigations were, however, performed on the most active series using a genetic approach based on RNA interference and highlighted a potential multi-target mechanism of action through topoisomerase II, mitotic spindle, HDAC and DNMT inhibition.

Antiproliferative activity of a new xanthone derivative from leaves of Garcinia nobilis Engl.

A new xanthone, mboudiexanthone (1), together with five known compounds, euxanthone (2), isogarcinol (3), garcinol (4), betulinic acid (5) and zeorin (6) were isolated from the leaves of Garcinia nobilis Engl. The structures were determined by 1D and 2D NMR techniques and X-ray diffraction for 6. The in vitro antiproliferative properties of isolated compounds were evaluated against the human breast cancer cell line MCF-7. All compounds showed an antiproliferative activity with an IC50 value down to ∼11 µM for isogarcinol.

2020

Compound isolation and biological activities of Piptadeniastrum africanum (hook.f.) Brennan roots

Ethnopharmacological relevance: The dicotyledonous plant Piptadeniastrum africanum (hook.f.) Brennan (Fabaceae) is used in traditional medicine to treat various human complaints including bronchitis, coughing, urino-genital ailments, meningitis, abdominal pain, treatment of wounds, malaria and gastrointestinal ailments, and is used as a purgative and worm expeller. Aim of the study: The present study describes the phytochemical investigation and the determination of the antimicrobial, antiplasmodial and antitrypanosomal activities of crude extract, fractions and compounds extracted from Piptadeniastrum africanum roots. Materials and methods: Isolated compounds were obtained using several chromatographic techniques. The structures of all compounds were determined by comprehensive spectroscopic analyses (1D and 2D NMR) and by comparing their NMR data with those found in literature. In vitro antimicrobial activity of samples was evaluated using the microdilution method on bacterial (Escherichia coli, Proteus mirabilis, Staphylococcus aureus) and fungal (Candida krusei) strains, while in vitro cell-growth inhibition activities were assessed against two parasites (Trypanosoma brucei brucei and Plasmodium falciparum strain 3D7). The cytotoxicity properties of samples were assayed against HeLa human cervical carcinoma. Results: Five compounds were isolated and identified as: tricosanol 1, 5α-stigmasta-7,22-dien-3-β-ol 2, betulinic acid 3, oleanolic acid 4 and piptadenamide 5. This is the first report of the isolation of these five compounds from the roots of P. africanum. The (Hex:EtOAc 50:50) fraction exhibited moderate antibacterial activity against P. mirabilis (MIC 250 μg/mL), while the other fractions and isolated compounds had weak antimicrobial activities. Only the EtOAc fraction presented a moderate antimalarial activity with an IC50 of 16.5 μg/mL. The MeOH crude extract and three fractions (Hexane, Hexane-EtOAc 25% and EtOAc-MeOH 25%) exhibited significant trypanocidal activity with IC50 values of 3.0, 37.5, 3.8 and 9.5 μg/mL, respectively. Conclusion: These results demonstrated a scientific rational of the traditional uses of P. africanum and indicate that this plant should be further investigated to identify some of the chemical components that exhibited the activities reported in this study and therefore may constitute new lead candidates in parasiticidal drug discovery.

Halogen bonding for molecular recognition: new developments in materials and biological sciences

This review highlights recent developments of halogen bonding in materials and biological sciences with a short discussion on the nature of the interaction.

2019

A comprehensive analysis of the protein-ligand interactions in crystal structures of Mycobacterium tuberculosis EthR

The Mycobacterium tuberculosis EthR is a member of the TetR family of repressors, controlling the expression of EthA, a mono-oxygenase responsible for the bioactivation of the prodrug ethionamide. This protein was established as a promising therapeutic target against tuberculosis, allowing, when inhibited by a drug-like molecule, to boost the action of ethionamide. Dozens of EthR crystal structures have been solved in complex with ligands. Herein, we disclose EthR structures in complex with 18 different small molecules and then performed in-depth analysis on the complete set of EthR structures that provides insights on EthR-ligand interactions. The 81 molecules solved in complex with EthR show a large diversity of chemical structures that were split up into several chemical clusters. Two of the most striking common points of EthR-ligand interactions are the quasi-omnipresence of a hydrogen bond bridging compounds with Asn179 and the high occurrence of π-π interactions involving Phe110. A systematic analysis of the protein-ligand contacts identified eight hot spot residues that defined the basic structural features governing the binding mode of small molecules to EthR. Implications for the design of new potent inhibitors are discussed.

2018

Crystal packing and theoretical analysis of halogen- and hydrogen-bonded hydrazones from pharmaceuticals. Evidence of type I and II halogen bonds in extended chains of dichloromethane

The supramolecular assembly of halogenated and hydroxyl hydrazones derived from two well known pharmaceuticals, isoniazid (IsX, where X = I, Br, OH) and hydralazine (HyX, where X = I, Br, OH), was studied by X-ray crystallography and theoretical methods. Crystal packing of IsI and HyI shows weak I…N and I…π halogen bonds, whereas the hydrogen bonds are dominant in the brominated scaffolds IsBr and HyBr. Although the calculated I…N interaction strength appears almost three times weaker than the O—H…N contacts in the isoniazid-based hydrazones, the higher directionality of the halogen bonds induces a linear and planar architecture of self-complementary tectons, observed only with the help of a bridging water molecule in the case of IsOH. Finally, the X-ray structure of HyOH is characterized by an unexpected linear arrangement of clathrated dichloromethane molecules bound through type I and II halogen bonds. This rare phenomenon, observed in less than ten structures, was studied by coupled cluster-based energy decomposition.

Biological activities of plant extracts from Ficus elastica and Selaginella vogelli: An antimalarial, antitrypanosomal and cytotoxity evaluation.

The cytotoxic, antiplasmodial, and antitrypanosomal activities of two medicinal plants traditionally used in Cameroon were evaluated. Wood of Ficus elastica Roxb. ex Hornem. aerial roots (Moraceae) and Selaginella vogelii Spring (Selaginellaceae) leaves were collected from two different sites in Cameroon. In vitro cell-growth inhibition activities were assessed on methanol extract of plant materials against Plasmodium falciparum strain 3D7 and Trypanosoma brucei brucei, as well as against HeLa human cervical carcinoma cells. Criteria for activity were an IC50 value < 10 μg/mL. The extract of S. vogelii did not significantly reduce the viability of P. falciparum at a concentration of 25 μg/mL but dramatically affected the trypanosome growth with an IC50 of 2.4 μg/mL. In contrast, at the same concentration, the extract of F. elastica exhibited plasmodiacidal activity (IC50 value of 9.5 μg/mL) and trypanocidal (IC50 value of 0.9 μg/mL) activity. Both extracts presented low cytotoxic effects on HeLa cancer cell line. These results indicate that the selected medicinal plants could be further investigated for identifying compounds that may be responsible for the observed activities and that may represent new leads in parasitical drug discovery.

2017

Discovery of Novel Potent Reversible and Irreversible Myeloperoxidase Inhibitors Using Virtual Screening Procedure

The heme enzyme myeloperoxidase (MPO) participates in innate immune defense mechanism through formation of microbicidal reactive oxidants. However, evidence has emerged that MPO-derived oxidants contribute to propagation of inflammatory diseases. Because of the deleterious effects of circulating MPO, there is a great interest in the development of new efficient and specific inhibitors. Here, we have performed a novel virtual screening procedure, depending on ligand-based pharmacophore modeling followed by structure-based virtual screening. Starting from a set of 727842 compounds, 28 molecules were selected by this virtual method and tested on MPO in vitro. Twelve out of 28 compounds were found to have an IC50 less than 5 μM. The best inhibitors were 2-(7-methoxy-4-methylquinazolin-2-yl)guanidine (28) and (R)-2-(1-((2,3-dihydro-1H-imidazol-2-yl)methyl)pyrrolidin-3-yl)-5-fluoro-1H-benzo[d]imidazole (42) with IC50 values of 44 and 50 nM, respectively. Studies on the mechanism of inhibition suggest that 28 is the first potent mechanism-based inhibitor and inhibits irreversibly MPO at nanomolar concentration.

Structural analysis of the interaction between spiroisoxazoline SMARt-420 and the Mycobacterium tuberculosis repressor EthR2.

Inhibition of transcriptional regulators of bacterial pathogens with the aim of reprogramming their metabolism to modify their antibiotic susceptibility constitutes a promising therapeutic strategy. One example is the bio-activation of the anti-tubercular pro-drug ethionamide, which activity could be enhanced by inhibiting the transcriptional repressor EthR. Recently, we discovered that inhibition of a second transcriptional repressor, EthR2, leads to the awakening of a new ethionamide bio-activation pathway. The x-ray structure of EthR2 was solved at 2.3 Å resolution in complex with a compound called SMARt-420 (Small Molecule Aborting Resistance). Detailed comparison and structural analysis revealed interesting insights for the upcoming structure-based design of EthR2 inhibitors as an alternative to revert ethionamide resistance in Mycobacterium tuberculosis.

Triple-stimuli responsive polymers with fine tuneable magnetic responses

The formation of multi-stimuli responsive polymers exhibiting magnetic, pH and light sensitivity is reported. After quaternization of tertiary amines along poly(2-(N,N-dimethylamino) ethyl methacrylate) (PDMAEMA) with varied alkyl and benzyl halides, a series of tetrahalogenoferrate(iii) salts were obtained by anion metathesis, conferring tailored and high magnetic responses. Experimental and theoretical Raman analyses allowed one to distinguish between the different magnetic anions present in the materials. This strategy was then implemented to the formation of multi-responsive compounds, by using random copolymers that incorporate various amounts of DMAEMA (∼40, 65 and 80%) and diazobenzene units. Partial or total quaternization of the dimethylamino end groups (10, 50 and 100%) followed by magnetic anion exchange afforded the magnetic-responsive copolymers, as evidenced by their magnetic susceptibility. Free ternary amino groups and diazobenzene moieties further brought pH and light sensitivity, giving rise to triple-stimuli responsive materials. This simple and rapid procedure offers the opportunity to fine tune the magnetic properties of remotely controlled smart devices.

Halogen bonded Borromean networks by design: topology invariance and metric tuning in a library of multi-component systems

A library of supramolecular anionic networks showing Borromean interpenetration has been prepared by self-assembly of crypt-222, several metal or ammonium halides, and five bis-homologous α,ω-diiodoperfluoroalkanes. Halogen bonding has driven the formation of these anionic networks. Borromean entanglement has been obtained starting from all the four used cations, all the three used anions, but only two of the five used diiodoperfluoroalkanes. As the change of the diiodoperfluoroalkane, the cation, or the anion has a different relative effect on the metrics and bondings of the self-assembled systems, it can be generalized that bonding, namely energetic, features play here a less influential role than metric features in determining the topology of the prepared tetra-component cocrystals. This conclusion may hold true for other multi-component systems and may function as a general heuristic principle when pursuing the preparation of multi-component systems having the same topology but different composition.

From Dynamic Combinatorial Chemistry to in Vivo Evaluation of Reversible and Irreversible Myeloperoxidase Inhibitors.

The implementation of dynamic combinatorial libraries allowed the determination of highly active reversible and irreversible inhibitors of myeloperoxidase (MPO) at the nanomolar level. Docking experiments highlighted the interaction between the most active ligands and MPO, and further kinetic studies defined the mode of inhibition of these compounds. Finally, in vivo evaluation showed that one dose of irreversible inhibitors is able to suppress the activity of MPO after inducing inflammation.

Connectivity and Topology Invariance in Self-Assembled and Halogen-Bonded Anionic (6,3)-Networks.

We report here that the halogen bond driven self-assembly of 1,3,5-trifluorotriiodobenzene with tetraethylammonium and -phosphonium bromides affords 1:1 co-crystals, wherein the mutual induced fit of the triiodobenzene derivative and the bromide anions (halogen bond donor and acceptors, respectively) elicits the potential of these two tectons to function as tritopic modules (6,3). Supramolecular anionic networks are present in the two co-crystals wherein the donor and the acceptor alternate at the vertexes of the hexagonal frames and cations are accommodated in the potential empty space encircled by the frames. The change of one component in a self-assembled multi-component co-crystal often results in a change in its supramolecular connectivity and topology. Our systems have the same supramolecular features of corresponding iodide analogues as the metric aspects seem to prevail over other aspects in controlling the self-assembly process.

In vitro antimicrobial activity of the methanol extract and compounds from the wood of Ficus elastica Roxb. ex Hornem. aerial roots

Ficus elastica Roxb. ex Hornem., an edible plant belonging to the family of Moraceae, is traditionally used against skin infections and allergies besides having diuretic properties. This study aimed at investigating the antimicrobial activity of the wood of F. elastica aerial roots against a set of bacteria (Staphylococcus aureus; Escherichia coli, Proteus vulgaris, Providencia stuartii and Pseudomonas aeruginosa) and a yeast (Candida albicans). A mixture of linear aliphatic alkanes with n-hexacosane as major compound, β-sitosterol, biochanin A, sitosteryl 3-O-β-D-glucopyranoside (1), elasticamide (2), elastiquinone (3) and ficusoside B (4) were purified and characterized. Antimicrobial activities, expressed as minimum inhibitory concentration (MIC), indicated that the methanol extract showed MIC of 39.1 μg/mL; the lowest values were obtained for 3 and 4, with MIC as low as 4.9 μg/mL, smaller than the values of reference antibiotics (25 μg/mL). Furthermore, as most of the studied samples exhibited Minimum Microbicidal Concentration/Minimum Inhibitory Concentration (MMC/MIC) ratios lower than 4, a microbicidal effect was clearly exhibited. The overall results provided evidence that the wood of F. elastica aerial roots, as well as some of its isolated components might be potential sources of new antimicrobial drugs.

2016

Characterization of chemical features of potent myeloperoxidase inhibitors.

Despite its important role in the immune system, myeloperoxidase (MPO) is implicated in a wide range of inflammatory syndromes due to its oxidative product HOCl. The oxidative damages caused by MPO make it a new target for developing promising anti-inflammatory agents. In this paper, we tried to understand the mechanism of MPO inhibition in order to facilitate the drug design, to develop more accurate virtual tests and to understand the structure-activity relationship.

Interplay between poly(ethylene oxide) and poly(L-lactide) blocks during diblock copolymer crystallization

The influence of composition and crystallization conditions on the behavior of double crystalline poly (ethylene oxide-b-l-lactide) (PEO-b-PLLA) diblock copolymers is investigated. Poly(l-lactide) contents in the synthesized copolymers vary from 50 to 91%, and the molecular weight of the PLLA block ranges from 2 to 20 kg mol-1, while that of the PEO block is kept constant at 2 kg mol-1. In bulk samples, DSC results show a synergistic interaction between the crystallization processes of the two blocks. The PEO block provides heterogeneities and exerts a plasticizing action which favors the crystallization of the PLLA block with a nucleation efficiency of 30%. In contrast, the subsequent crystallization of the PEO block is subject to two opposing effects: (a) the nucleating action of PLLA crystals and (b) the topological and geometrical constraints imposed by PLLA crystals, especially when the PEO content is 20 wt% or less. In the case of ultra thin films, block copolymers with PEO contents equal or smaller than 20 wt% form distorted PLLA single crystals when crystallized from the melt. However, upon increasing the PEO content in the system to 33 wt% (by blending or copolymerization), the distortions disappear and the angle between the {110} growth faces changes from 140° to 121°, since the PEO block acts as a solvent or plasticizer for the PLLA block during the crystallization process. PEO incorporation can therefore tailor the rate and morphology of PLLA block crystallization. TEM and AFM studies allowed direct observation of the PEO block dendritic crystals on the surface of lozenge-shaped PLLA crystals previously formed during cooling from the melt.

Identification of compounds with anti-proliferative activity from the wood of Ficus elastica Roxb. ex Hornem. aerial roots.

The natural products fromplants still remain an important source of pharmaceuticals. In the current study, methanolicwood extracts of Ficus elastica Roxb. ex Hornem. (Moraceae) aerial roots were screened for anti-cancer activity. Using bioassay-guided fractionation, three new compounds, elasticamide (1), elastiquinone (2) and ficusoside B (3), together with four known compounds, were isolated. The structures of the new compounds were established by means of extensive spectroscopic analyses (1D and 2D NMR, HR-ESI-MS, as well as IR and UV) and by comparison of their spectroscopic data with those reported for structurally related molecules. The isolated compounds were afterwards evaluated for their anti-proliferative effect on six human cancer cell lines (U373n and Hs683 glioblastoma, MCF7 and A549 NSCLC carcinoma, and B16F10 and SK-MEL-28 melanoma) using colorimetric MTT assay. Most notably, elastiquinone (2) showed cytotoxic activity with IC50 = 14 μM against B16F10 melanoma cells, whereas the peracetylated form of ficusoside B (3a) displayed the lowest IC50 value (11 μM) against U373n gliomacell lines. Elasticamide (1) and ficusoside B (3) exhibited aweak cytotoxicity with IC50 values ≥88 μM. The results of this investigation demonstrate that the wood of F. elastica aerial roots might be a potential source for identifying new compounds with potent anti-proliferative activity.

Halogen bonding in multi-connected 1,2,2-triiodo-alkene involving geminal and/or vicinal iodines: A crystallographic and DFT study

Four halogen-bonded arrangements of (1,2,2 - triiodovinyl) benzene involving geminai and/or vicinal iodine atoms were studied both by X-ray diffraction and density functional theory (DFT). Crystallographic data show weaker XB-type interactions for the iodine atom geminal to the phenylring, which is corroborated by DFT-optimized structures of 1:1, 1:2 and 1:3 (1,2,2-triiodovinyl)benzene/pyridine complexes. In addition, a theoretical model reflects an interplay existing between these conjugated and multi-connected sites, highlighting the weakening of the halogen bonds when the number of partners is increased.

In vitro antimicrobial and anti-proliferative activities of plant extracts from Spathodea campanulata, Ficus bubu and Carica papaya

Trifluoromethyl nitrogen heterocycles: Synthetic aspects and potential biological targets

Recent advances regarding the synthetic chemistry of fluorinated aziridines, azetidines, pyrrolidines and their lactam/amino acid counterparts are presented. These heterocycles are of high importance both as building blocks for more complex structures and as active parts of medicinal chemistry-oriented compounds.

2015

In vitro Evaluation of Antimicrobial and Antiproliferative Activities for Compounds Isolated from the Ficus bubu Warb. (Moraceae) Fruits: Chemotaxonomic Significance

Fluorinated conjugated polymers in organic bulk heterojunction photovoltaic solar cells

The photovoltaic technology represents a major renewable energy source to harnes the solar power. Over the last two decades, the development of solution-processed bulk heterojunction polymer solar cells has attracted a considerable interest. This has resulted in a significant efficiency improvement through innovation of device architectures and molecular structure design of donor polymers. In this regard, the introduction of fluorinated units along the conjugated backbone has emerged as a successful strategy for further fine-tuning the physical and chemical properties of conducting polymers. In this review, we highlight recent strategies aiming at improving the solar cell performance by variable fluorine substitution of repeating units. Fluorination was found to achieve a modulation of HOMO and LUMO energy levels and optical properties to some extent. Moreover, intermolecular interactions involving fluorine atoms have a significant influence on blend film morphology. The resulting organic photovoltaic solar cells endowed some of the highest power conversion efficiency values reported to date. © 2015 Elsevier Ltd.

Halogen bonding in polymer science: From crystal engineering to functional supramolecular polymers and materials

Halogen bonding (XB) is commonly defined as a non-covalent bond where halogen atoms (X

Pyrene-end-functionalized poly(L-lactide) as an efficient carbon nanotube dispersing agent in poly(L-lactide): mechanical performance and biocompatibility study

In order to improve the mechanical properties of poly(L-lactide) (PLLA) based implants, a study was made of how far well dispersed multi-walled carbon nanotubes (MWCNTs) within a PLLA matrix were able to positively affect these properties. To this end, pyrene-end-functionalized poly(L-lactide) (py-end-PLLA) was evaluated as a dispersing agent. Transmission electron microscopy (TEM) analyses and mechanical tests of MWCNTs-based materials demonstrated an enhancement of MWCNT dispersion in the PLLA matrix and improved Young’s modulus (E) when 4 wt% of py-end-PLLA was used as the dispersing agent. Subsequently, the bioacceptance of PLLA/py-end-PLLA/MWCNTs nanocomposites was evaluated using human bone marrow stromal cells (HBMC) in vitro . The inclusion of py-end-PLLA and MWCNTs supported HBMC adhesion and proliferation. The expression levels of the bone-specific markers indicated that the cells kept their potential to undergo osteogenic differentiation. The results of this study indicate that the addition of MWCNT combined with py-end-PLLA in PLLA/py-end-PLLA/MWCNTs nanocomposites may widen the range of applications of PLLA within the field of bone tissue engineering thanks to their mechanical strength and cytocompatibility.

2014

Synthesis of alpha-CF3 azanorbornene and azetidines by aza Diels-Alder or iodine-mediated cyclizations: Application in ROMP and ligand design

We report the synthesis of several new α-trifluoromethylated nitrogen heterocycles, among which azanorbornene and azetidine derivatives, by aza Diels-Alder or iodine-mediated cyclizations. These building blocks were used as starting materials for the formation of fluorinated polymers by ROMP or for ligand design through substitution and click reactions.

Tilted fiber Bragg gratings as a new sensing device for in situ and real time monitoring of surface-initiated polymerization

The in situ and real time monitoring of surface-initiated polymerization was performed through tilted fiber Bragg gratings. The combination of gratings and stimuli responsive polymers represents a very appealing technology for the development of new sensing devices. © 2014 The Royal Society of Chemistry.

The 1:1 co-crystal of triphenyl(2,3,5,6-tetrafluorobenzyl)phosphonium bromide and 1,1,2,2-tetrafluoro-1,2-diiodoethane

The title compound, C25H18F4P +·Br-·C2F4I 2, is a 1:1 co-crystal of triphenyl(2,3,5,6-tetrafluorobenzyl) phosphonium (TTPB) bromide and 1,1,2,2-tetrafluoro-1,2-diiodoethane (TFDIE). The crystal structure consists of a framework of TTPB cations held together by C-H⋯Br interactions. In this framework, infinite channels along [100] are filled by TFDIE molecules held together in infinite ribbons by short F⋯F [2.863(2)-2.901(2)Å] interactions. The structure contains halogen bonds (XB) and hydrogen bonds (HB) in the bromide coordination sphere. TFDIE functions as a monodentate XB donor as only one I atom is linked to the Br- anion and forms a short and directional interaction [I⋯Br- 3.1798(7)Å and C-I⋯Br- 177.76(5)°]. The coordination sphere of the bromide anion is completed by two short HBs of about 2.8Å (for H⋯Br) with the acidic methylene H atoms and two longer HBs of about 3.0Å with H atoms of the phenyl rings. Surprisingly neither the second iodine atom of TFDIE nor the H atom on the tetrafluorophenyl group make any short contacts.

Interplay between halogen bonding and lone pair-Pi interactions: A computational and crystal packing study

The supramolecular organization of modified thiophenes resulting from N⋯I halogen bonding (XB) has been studied. X-ray diffraction analyses of two polymorphs of the same supramolecular complex showed an arrangement controlled by halogen-bonded pyridyl and tetrafluoroiodobenzene rings, one case with and the other without the presence of two different lone pair (lp)⋯π interactions, namely O⋯pyridyl and I⋯ tetrafluoroiodobenzene contacts. To shed light on the interplay between these interactions, quantum mechanical calculations were performed at the ωB97X-D/6-31+G(d,p) level on both systems in the gas phase. The longer N⋯I distance observed in the crystal structure without lp⋯π interactions was also corroborated by dispersion-corrected DFT. These results represent the first case in which a synergy between lp⋯π interactions and XB is observed experimentally and confirmed by calculations. Getting organized: X-ray diffraction analyses of two polymorphs of a supramolecular thiophene complex show an arrangement controlled by N⋯I halogen bonding (XB), one case with and the other without the presence of two different lone pair (lp)⋯π interactions, namely O⋯pyridyl and I⋯tetrafluoroiodobenzene contacts (see figure). Quantum mechanical calculations confirm the interplay between concomitant XB and lp⋯π interactions. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

2013

Polylactide stereocomplex crystallization prompted by multiwall carbon nanotubes

Synthesis of binary-patterned brushes by combining atom transfer radical polymerization and ring-opening polymerization

High-resolution structure of a papaya plant-defence barwin-like protein solved by in-house sulfur-SAD phasing

The first crystal structure of a barwin-like protein, named carwin, has been determined at high resolution by single-wavelength anomalous diffraction (SAD) phasing using the six intrinsic S atoms present in the protein. The barwin-like protein was purified from Carica papaya latex and crystallized in the orthorhombic space group P212121. Using in-house Cu Kα X-ray radiation, 16 cumulative diffraction data sets were acquired to increase the signal-to-noise level and thereby the anomalous scattering signal. A sequence-database search on the papaya genome identified two carwin isoforms of 122 residues in length, both containing six S atoms that yield an estimated Bijvoet ratio of 0.93% at 1.54 Å wavelength. A systematic analysis of data quality and redundancy was performed to assess the capacity to locate the S atoms and to phase the data. It was observed that the crystal decay was low during data collection and that successful S-SAD phasing could be obtained with a relatively low data multiplicity of about 7. Using a synchrotron source, high-resolution data (1 Å) were collected from two different crystal forms of the papaya latex carwin. The refined structures showed a central β-barrel of six strands surrounded by several α-helices and loops. The β-barrel of carwin appears to be a common structural module that is shared within several other unrelated proteins. Finally, the possible biological function of the protein is discussed.

Magnetic poly(vinylpyridine)-coated carbon nanotubes: an efficient supramolecular tool for wastewater purification.

Herein, we report the first example of a supramolecular carbon nanotube (CNT)-based magnetic depolluting agent for divalent metal ion (M(2+)) removal from aqueous solutions. In particular, magnetic multi-walled carbon nanotubes (m-MWCNTs) coated with poly(vinylpyridine) (PVPy) self-aggregate in aqueous solutions that contain divalent metal ions (such as Zn(2+), Cu(2+) and Pb(2+)) to form tight insoluble bundles in which the M(2+) ions remain trapped through pyridyl-M(2+)-pyridyl interactions. Magnetic filtration ultimately affords the efficient separation of the depolluted solution from the precipitated M(2+)-CNT agglomerates. Upon acid treatment, the supramolecular threads could be disassembled to afford the free CNT-polymer hybrid, thus allowing recycling of the depolluting agent. All materials and complexation/decomplexation steps were thoroughly characterised by using thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), transmission and scanning electron microscopy (TEM and SEM, respectively). The quantification of the M(2+) residual concentrations in water was evaluated by using inductively coupled plasma optical emission spectroscopy (ICP-OES), which showed that, depending on the metal cation, this material can remove up to 99% of the contaminant.

Halogen bonding at work: Recent applications in synthetic chemistry and materials science

Halogen bonding has recently entered the arena of reliable and valuable non-covalent interactions for the construction of supramolecular complexes. A step further, this highlight provides some new insights related to the design of advanced functional materials encompassing halogen bonded mesomorphic and electronic components. Other recent applications have been extended to various aspects of solution phase recognition (catalysis, ion sensing and resolution) and macromolecular organizations (porous, polymeric and hybrid systems). © 2013 The Royal Society of Chemistry.

2012

Ceramide, cerebroside and triterpenoid saponin from the bark of aerial roots of Ficus elastica (Moraceae).

Three compounds, ficusamide (1), ficusoside (2) and elasticoside (3), were isolated from the bark of aerial roots of Ficus elastica (Moraceae), together with nine known compounds, including four triterpenes, three steroids and two aliphatic linear alcohols. The chemical structures of the three compounds were established by extensive 1D and 2D NMR spectroscopy, mass spectrometry and by comparison with published data. The growth inhibitory effect of the crude extract and isolated compounds was evaluated against several microorganisms and fungi. The cytotoxicity against human cancer cell lines was also assessed. Ficusamide (1) displayed a moderate in vitro growth inhibitory activity against the human A549 lung cancer cell line and a strong activity against Staphylococcus saprophyticus, while elasticoside (3) showed a potent activity on Enterococcus faecalis.

Surface-initiated controlled polymerization as a convenient method for designing functional polymer brushes

Imidazolium End-Functionalized ATRP Polymers as Directing Agents for CNT Dispersion and Confinement

Imidazolium end-functionalized poly(butyl acrylate) and polystyrene (co)polymers (Im-PnBuA, Im-PSty, and Im-PnBuA-b-PSty are synthesized via ATRP. The controlled character of the polymerization reactions is highlighted by SEC and MALDI-TOF MS analyses. Subsequently, the polymers are tested as dispersing/compatibilizing agents for CNTs in polymer matrices. When CNTs are challenged with a mixture of Im-PnBuA and Im-PSty, the CNTs are mainly located in the PnBuA phase. In contrast, the Im-PnBuA-b-PSty block copolymer enables CNT confinement in the PSty phase. By selecting the proper ω-imidazolium polymer, it is possible to direct the CNT confinement toward a specific polymer phase within polymer mixtures.

2011

Synthesis of clicked imidazolium-containing biosourced copolymers and application in carbon nanotube dispersion

New polyesters incorporating a variable quantity of imidazolium rings along the backbone are synthesized by Huisgen 1,3-dipolar cycloaddition (“click” reaction). Subsequently, the imidazolium-grafted copolymers reveal an efficient dispersing ability toward the carbon nanotubes (CNTs) through supramolecular interactions in organic media. Interestingly, these compounds offer a simple and reliable strategy to control the quantity of dispersed CNTs as a function of imidazolium content. This approach is particularly suitable for the elaboration of biosourced and biodegradable materials based on poly(butylene succinate) with high-performance properties.

Design of crosslinked semi-crystalline poly(ε-caprolactone)-based networks with one-way and two-way shape memory properties through Diels-Alder reactions

Cross-linked poly(ε-caprolactone) (PCL)-based polyesterurethane (PUR) systems have been synthesized through Diels-Alder reactions by reactive extrusion. The Diels-Alder and retro-Diels-Alder reactions proved to be useful for enhancing the molecular motion of PCL-based systems, and therefore their crystallization ability, in the design of cross-linked semicrystalline polymers with one-way and two-way shape-memory properties. Successive reactions between α,ω-diol PCL (PCL2), furfuryl alcohol, and methylene diphenyl 4,4′-diisocyanate straightforwardly afforded the α,ω-furfuryl PCL-based PUR systems, and subsequent Diels-Alder reactions with N,N-phenylenedimaleimide afforded the thermoreversible cycloadducts. The cross-linking density could be modulated by partially replacing PCL-diol with PCL-tetraol. Interestingly, the resulting PUR systems proved to be semicrystalline cross-linked polymers, the melting temperature of which (close to 45 °C) represented the switching temperature for their shape-memory properties. Qualitative and quantitative measurements demonstrated that these PUR systems exhibited one-way and two-way shape-memory properties depending on their cross-linking density.

Self-Complementary Nonlinear Optical-Phores Targeted to Halogen Bond-Driven Self-Assembly of Electro-Optic Materials

Poly(ethylene oxide)-b-poly(L-lactide) diblock copolymer/carbon nanotube-based nanocomposites

Supramolecular interactions as a powerful tool for the design of high-performance poly(L-lactide)/carbon nanotube nanocomposites

Thermal degradation of Poly(L-lactide)

Reversible positioning at submicrometer scale of carbon nanotubes mediated by pH-sensitive poly(amino-methacrylate) patterns

2010

Structure-function relationships in liquid-crystalline halogen-bonded complexes

New liquid-crystalline materials were prepared by self-assembly driven by halogen bonding between a range of 4-alkoxystilbazoles, 4-alkyl-, and 4-alkoxy-substituted pyridines as halogen-bonding acceptors, and substituted derivatives of 4-iodotetrafluorophenyl as halogen-bonding donors. Despite the fact that the starting materials are not mesomorphic, the dimeric, halogen-bonded complexes obtained exhibited nematic and SmA phases, depending on the length of the alkyl chains present on the components. The modularity of this approach also led to new chiral mesogens starting from non-mesomorphic chiral compounds.

Synthesis and supramolecular organization of regioregular polythiophene block oligomers.

The self-assembly of functional polythiophenes was studied by a bottom-up approach "from molecule to polymer". The synthesis and the X-ray structure of 2,5-dibromo-3-styryl and 3-2',3',4',5',6'-pentafluorostyryl-thiophenes revealed a supramolecular arrangement controlled by pi-pi interactions between the aromatic rings. A [2 + 2] photocyclization reaction in the solid state of (E)-1-2',5'-dibromo-3'-thienyl-2-pentafluorophenylethene triggers the formation of a rare cycloadduct comprising thiophene rings. The X-ray analysis confirmed its rctt stereochemistry. The synthesis of P3HT-b-P3ST and P3HT-b-P3STF block oligomers was achieved by a GRIM method in good yields. An indirect proof of well-defined nanostructured organization was provided by the partial photocyclization of pendant styryl moieties under UV irradiation.

Halogen-bonded and interpenetrated networks through the self-assembly of diiodoperfluoroarene and tetrapyridyl tectons

Imidazolium end-functionalized poly(L-lactide) for efficient carbon nanotube dispersion

Poly(amino-methacrylate) as versatile agent for carbon nanotube dispersion

Controlled room temperature ROP of L-lactide by ICl3

(E)-3-(2,3,4,5,6-Penta-fluoro-styr-yl)thio-phene

The reaction of thio-phene-3-carboxaldehyde and perfluoro-benzyl-triphenyl- phospho-nium bromide in the presence of sodium hydride gave the title compound, C12H5F5S, in 70% yield. The thiophene and perfluorophenyl groups form a dihedral angle of 5.4 (2)°. The structure is characterized by a head-to-tail organization in a columnar arrangement due to π-π inter-actions between the thio-phene and penta-fluoro-phenyl rings with centroid-centroid distances in the range 3.698 (2)-3.802 (2) Å.

2009

Synthesis, polymerization and conducting properties of an ionic liquid-type anionic monomer

Ionic IPNs as novel candidates for highly conductive solid polymer electrolytes

Halide anions driven self-assembly of haloperfluoroarenes

2008

Halogen Bonding in Supramolecular Chemistry

Halogen bonding (XB) is the noncovalent interaction where halogen atoms function as electrophilic species. The energetic and geometrical features of the interaction are described along with the atomic characteristics conferring to molecules the specific ability to interact via XB. Halogen bonding impacts all fields where the control of intermolecular recognition and self-assembly processes plays a key role. In this review, some heuristic principles are presented to develop a rational crystal engineering based on halogen bonding. The functional potential of the interaction is also shown by applications in the field of liquid crystals, magnetic and conducting materials, and biological systems.

2-(2,3,5,6-Tetrafluoro-4-iodo-phenylamino)-ethanol

Mutual induced coordination in halogen-bonded anionic assemblies with (6.3) cation-templated topologies

Binding Energies and 19F Nuclear Magnetic Deshielding in Paramagnetic Halogen Bonded Complexes of TEMPO with Haloperfluorocarbons

Dendrimeric tectons as building blocks in halogen bonded supramolecular networks

Mesogenic, trimeric, halogen-bonded complexes from alkoxystilbazoles and 1,4-dihalotetrafluorobenzene

2007

Highly interpenetrated networks supported by N⋅⋅⋅I halogen bonding

Halogen bonding (XB) has been used to assemble tetrakis(4-pyridyl)pentaerythritol (tetradentate XB acceptor) with different α,ω-diiodoperfluoroalkanes (bidentate XB donors) or tetrakis(4-iodotetrafluorophenyl)pentaerythritol (tetradentate XB donor). The remarkable linearity of the XB formed, the rodlike character of α,ω-diiodoperfluoroalkanes and the mutual complementarities of pentaerythritol partners, translate the three-dimensional character of the XB acceptor into open primary networks, which interpenetrate to avoid the presence of voids and to ensure segregation of the modules. Two-dimensional (2D) square 44 layers (sql) with fourfold and fivefold interpenetration, as well as an eightfold diamondoid network (dia) of class Ia and a remarkable tenfold dia network of class IIIa, have been obtained.

Tuning second-order NLO responses through halogen bonding.

As a function of the ability of the solvent to behave as acceptor of halogen bonding, the NLO-phores under study give rise to microbeta(lambda) values ranging from +192 x 10(-48) esu to -465 x 10(-48) esu.

Engineering functional materials by halogen bonding

4,4'-Bipyridine-1,3-diiodo-2,4,5,6-tetrafluorobenzene

2006

Solid state synthesis under supramolecular control of a 2D heterotetratopic self-complementary tecton for halogen bonding

Hybrid Calixarene /Inorganic Salt/ Diiodoperfluorocarbon Supramolecular Assemblies

Metric Engineering of Supramolecular Borromean Rings

2005

One-pot synthesis of doubly unsaturated trifluoromethyl amines: easy access to CF3-substituted piperidinesur

A straightforward route to trifluoromethyl analogs of piperidines is described. These syntheses involve a Barbier-type allylation reaction of trifluoroacetaldimines, followed by N-allylation (one-pot), and ring-closing metathesis. An efficient asymmetric version is also reported (>98 % de). Functionalized heterobicyclic compounds can also be obtained by a Pauson-Khand reaction. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Cyclotriphosphazene [N3P3(2,2'-dioxybiphenyl)2-(4-pyridinoxy)2] and its halogen bonded complex with 1,4-diiodotetrafluorobenzene

2004

Crystal engineering of brominated tectons

A novel phosphorus-carbon bond formation by ring opening with diethyl phosphite of oxazolines derived from serine

2003

Efficient synthesis of β-halogeno protected L-alanines and their β-phosphonium derivatives

Stereoselective Barbier-Type Allylation Reaction of Trifluoromethyl Aldimines

NMR enantiodifferentiation of triphenylphosphonium salts by chiral hexacoordinated phosphate anions

2001

Triphenylphosphonium salts bearing an L-alanyl substituent