Giorgio Grisci

A Click Chemistry-Based “Grafting Through” Approach to the Synthesis of a Biorelevant Polymer Brush

A new biorelevant polymer brush showing a polybenzofulvene backbone was synthesized by a “grafting through” approach based on click chemistry and spontaneous polymerization reactions. The easy polymerization of the relatively complex monomer (6-MOEG-9-TM-BF3k) suggests the existence of a particularly efficient recognition process capable of pre-organizing the monomer molecules for the spontaneous polymerization. 13C-NMR spectroscopy as well as UV-vis and fluorescence spectroscopy suggested for poly-6-MOEG-9-TM-BF3k the features of a vinyl (1,2) π-stacked polymer. The new polybenzofulvene derivative was found to interact with water at room temperature to give clear water solutions, but TEM analysis demonstrated the presence of macromolecular aggregates showing dimensions larger than those suggested by SEC-MALS analysis for the isolated macromolecules. DLS studies confirmed the presence of objects showing average dimensions in the range of 200–300 nm and suggested thermoresponsive colloidal properties for poly-6-MOEG-9-TM-BF3kmacromolecules. Finally, owing to its favourable absorption/emission properties and water solubility, the interaction of poly-6-MOEG-9-TM-BF3k with live cells was studied by fluorescence microscopy experiments, which revealed that the polymer brush was unable to enter live cells and alter cell morphology.

Synthesis and characterization of charge-transporting π-stacked polybenzofulvene derivatives

Two new benzofulvene derivatives bearing two or three methoxy substituents on the benzene ring were synthesized and induced to polymerize spontaneously in order to investigate the photophysical and electronic properties of the corresponding polymers. The photophysical features of the newly synthesized polymers suggested a high degree of π-stacking both in the solid state and in diluted solutions, and the large Stokes shift was interpreted in terms of an efficient energy transfer within the excimer. Absorption and emission features in the solid state were found to be similar to those in diluted solutions and the stable PL quantum yield was considered a promising feature with regard to the potential applications of the polymers in light emitting devices. Finally, the remarkable hole mobility shown by poly-4,5,6-MO-BF3k along with the enhancing effect of the methoxy substituents in the charge mobility opens up new routes to the development of materials potentially useful in optoelectronics.

Highly emissive supramolecular assemblies based on π-stacked polybenzofulvene hosts and a benzothiadiazole guest

Two new benzofulvene derivatives bearing a fluorene chromophore in different positions of the phenylindene scaffold were synthesized and induced to polymerize spontaneously. The photophysical investigation evidenced the role of the substitution topology of the monomeric units in the optical properties of the corresponding polymers. In particular, the polymer emission efficiency was found to improve both in solution and in the solid state when the fluorene residue enhances monomer conjugation and rigidity. The ability of this newly synthesized class of polymers to self-organize in supramolecular structures is evidenced through a study on blends with a benzothiadiazole based dye at different concentrations. Aggregation quenching processes of the dye are sharply reduced and complete resonant energy transfer from the polymer to the dye is reached even at 1% dye concentration. The peculiar ability of this new class of π-stacked polymers to self-assemble in such a supramolecular organization suggests their use as platforms for the design of more complex nanostructured films with enhanced optical and optoelectronic properties.

Design, Synthesis, and Biological Evaluation of Imidazo[1,5-a]quinoline as Highly Potent Ligands of Central Benzodiazepine Receptors

A series of imidazo[1,5-a]quinoline derivatives was designed and synthesized as central benzodiazepine receptor (CBR) ligands. Most of the compounds showed high CBR affinity with Ki values within the submicromolar and subnanomolar ranges with interesting modulations in their structure-affinity relationships. In particular, fluoroderivative 7w (Ki = 0.44 nM) resulted in the most potent ligand among the imidazo[1,5-a]quinoline derivatives described so far. Overall, these observations confirmed the assumption concerning the presence of a large though apparently saturable lipophilic pocket in the CBR binding site region interacting with positions 4 and 5 of the imidazo[1,5-a]quinoline nucleus. The in vivo biological characterization revealed that compounds 7a,c,d,l,m,q,r,w show anxiolytic and antiamnestic activities without the unpleasant myorelaxant side effects of the classical 1,4-BDZ. Furthermore, the effect of 7l,q,r, and 8i in lowering lactate dehydrogenase (LDH) release induced by ischemia-like conditions in rat brain slices suggested neuroprotective properties for these imidazo[1,5-a]quinoline derivatives.

Bithiophene-based polybenzofulvene derivatives with high stacking and hole mobility

Four new benzofulvene derivatives bearing bithiophene chromophores at two different key positions of the phenylindene scaffold were prepared in order to evaluate the role of different chromophores in the optoelectronic features of polybenzofulvene derivatives. The results of the photophysical studies showed that the optical properties of the newly-synthesized bithiophene-functionalized polymers were affected by both the polymer enchainment and the substitution topology of the monomeric units. On the other hand, the hole-mobility appeared to be affected to a lesser extent, but the best performances were obtained in poly-6-HBT-BF3k showing the strongest bithiophene side chain packing. This work demonstrates that the optoelectronic properties of polybenzofulvene derivatives can be optimized by a targeted chemical design such as side chain engineering.

Self-assembly of a water soluble perylene and surfactant into fluorescent supramolecular ensembles sensitive to acetylcholinesterase activity

The modulation of assembly/disassembly of perylene diimide derivatives (PDIs) represents an intriguing challenge for fluorescence sensing purposes. Herein, an aminoacid-functionalized PDI (PDI-Thr) is selected as a conformationally-sensitive probe which transduces the modification of its aggregation state into an optical response. Photoluminescence measurements reveal that the emission of PDI-Thr in aqueous solution can be finely modulated by a cationic surfactant, myristoylcholine chloride (MyrCh). Fluorescence sensing studies illustrate that the PDI-Thr/MyrCh ensembles exhibit an emission intensity variation in response to the enzymatic activity of acetylcholinesterase, which is able to reverse the surfactochromic effect by catalyzing the hydrolysis of MyrCh. Detailed NMR investigations elucidate the supramolecular mechanism behind the sensing behavior. This study sheds light on the synergistic combination of electrostatic and hydrophobic interactions occurring between PDI-Thr and MyrCh, leading to the fluorescent ensemble which is responsible for the sensing performance. The discussed results outline that the development of fluorophore/surfactant ensembles based on water soluble PDIs have great potential for the label-free sensing of a wide range of analytes and enzymes.

Hyaluronan-coated polybenzofulvene brushes as biomimetic materials

Hyaluronic acid (HA) forms pericellular coats in many cell types that are involved in the early stages of cell adhesion by interacting with the CD44 receptor. Based on the largely recognized overexpression of the CD44 receptor in tumor tissues, a polybenzofulvene molecular brush has been enveloped into hyaluronan shells to obtain a tri-component polymer brush (TCPB) composed of intrinsically fluorescent backbones bearing nona(ethylene glycol) arms terminated with low molecular weight HA macromolecules. The nanoaggregates obtained in TCPB water dispersions were characterized on the basis of dimensions, zeta potential, and in vitro cell toxicity. This biomimetic multifunctional material bearing HA on the surface of its cylindrical brush architecture showed promising prerequisites for the preparation of nanostructured drug delivery systems.

Side chain engineering in π-stacked polybenzofulvene derivatives bearing electron-rich chromophores for OLED applications

In order to obtain new polymeric materials endowed with improved optoelectronic performances, suitable side chain engineering was designed to insert different chromophores showing electron donating ability [i.e. triphenylamine (TPA) and 9-methylcarbazole (MCBZ) residues] in two different key positions (i.e. 6 and 4′) of the 3-phenylindene scaffold of the polybenzofulvene monomeric units. Among the four newly-synthesized polybenzofulvene derivatives, those bearing triphenylamine moieties were found to show higher emissive properties with respect to the corresponding carbazole derivatives. Moreover, the preliminary OLED devices prepared with the triphenylamine-based polymers showed promising features, but the role of the aggregation process in affecting the emission properties of poly-6-TPA-BF3k suggested that extensive device development studies are required in order to maximize polybenzofulvene performances in OLED applications.

Wound healing properties of hyaluronan derivatives bearing ferulate residues

HAFA macromolecules were designed as graft copolymers combining ferulic acid (FA) structure and the hyaluronic acid (HA) backbone linked through an ester bond. These materials were prepared by feruloylation of HA with bisimidazolide 3 [i.e. (E)-4-(3-(1H-imidazol-1-yl)-3-oxoprop-1-enyl)-2-methoxyphenyl 1H-imidazole-1-carboxylate] and obtained with different grafting degree (GD) values, which could be tuned by applying suitable reaction conditions. Among the numerous applications envisioned for HAFA graft copolymers on the basis of the physico-chemical, biological, and pharmacological properties of the starting natural products and the grafting-derived features such as physical cross-linking, potential wound healing properties have been evaluated in vitro and in vivo in preclinical models. In human keratinocyte (HaCaT) cells, our data showed the ability of HAFA-17 (GD = 7%) to ameliorate the in vitro scratch wound significantly with respect to the control HA and FA alone, and this effect was associated with the ability of HAFA-17 to also induce keratinocyte proliferation as determined by BrdU assay. In addition, experiments on wound healing in SKH1 mice confirmed the ability of HAFA-17 to improve the wound closure rate also in vivo. Overall, the data presented herein suggest HAFA-17 as a possible future drug for the therapeutic treatment of acute and chronic wounds.

Self-assembled periodic patterns on the optical fiber tip by microsphere arrays

In this work, we report a fabrication route for self-assembling periodic patterns on optical fiber tips. The technique is based on self-assembling polystyrene microspheres at the air/water interface and on successive transferring of the monolayer colloidal crystal on the fiber tip. By applying to the fiber further treatments like particle size reduction, metal coating and sphere removal, different periodic structures are conveniently realized. The results obtained indicate that self-assembly technique affords opportunity to create on the optical fiber tip dielectric and metallic-dielectric spheres’ arrays with a feature size down to a submicron scale or metallic patterns with a few hundred nanometers at low fabrication costs.