Mariangela Boccalon

Metal-organic transmembrane nanopores.

A stable tetraporphyrin metallacycle with Re(I) corners (1) is capable of forming nanopores in a liposomial membrane, provided that the porphyrin units are properly functionalized with peripheral carboxylic acid residues that, by establishing an hydrogen bond network, allow the formation of dimers that span the depth of the membrane.

Design, Synthesis and Characterisation of Guanosine-Based Amphiphiles

A small library of sugar-modified guanosine derivatives has been prepared, starting from a common intermediate, fully protected on the nucleobase. Insertion of myristoyl chains and of diverse hydrophilic groups, such as an oligoethylene glycol, an amino acid or a disaccharide chain, connected through in vivo reversible ester linkages, or of a charged functional group provided different examples of amphiphilic guanosine analogues, named G1-G7 herein. All of the sugar-modified derivatives were positive in the potassium picrate test, showing an ability to form G-tetrads. CD spectra demonstrated that, as dilute solutions in CHCl(3), distinctive G-quadruplex systems may be formed, with spatial organisations dependent upon the structural modifications. Two compounds, G1 and G2, proved to be good low-molecular-weight organogelators in polar organic solvents, such as methanol, ethanol and acetonitrile. Ion transportation experiments through phospholipid bilayers were carried out to evaluate their ability to mediate H(+) transportation, with G5 showing the highest activity within the investigated series. Moreover, G3 and G5 exhibited a significant cytotoxic profile against human MCF-7 cancer cells in in vitro bioassays.

Design, Synthesis and Characterisation of a Fluorescently Labelled CyPLOS Ionophore

A novel fluorescently labelled synthetic ionophore, based on a cyclic phosphate-linked disaccharide (CyPLOS) backbone and decorated with four tetraethylene glycol tails carrying dansyl units, has been synthesised in 12 steps in 26% overall yield. The key intermediate in the synthetic strategy is a novel glucoside building block, serving through its 2- and 3-hydroxy groups as the anchor point for flexible tetraethylene glycol tentacles with reactive azido moieties at their ends. To test the versatility of this glucoside scaffold, it was preliminarily functionalised with a set of diverse probes--as fluorescent, redox-active or hydrophobic tags--either by reduction of the azides followed by condensation with activated carboxylic acid derivatives, or by a direct coupling with a terminal alkyne in a Cu(I)-promoted 1,3-dipolar cycloaddition. Tagging of the monomeric building block with dansyl residues allowed us to prepare a fluorescent, amphiphilic macrocycle, which was investigated for its propensity to self-aggregate in CDCl(3)--studied by means of concentration-dependent (31)P NMR spectroscopy experiments--and in aqueous solution, in which combined dynamic light scattering (DLS) and small-angle neutron scattering (SANS) measurements provided a detailed physico-chemical analysis of the self-assembled systems, mainly organised in the form of large vesicles. Its ion-transport properties through phospholipid bilayers, determined by HPTS fluorescence assays, showed this compound to be more active than the previously synthesised CyPLOS congeners. Solvent-dependent fluorescence changes for the labelled ionophore in liposome suspension established that the dansyl moieties are dispersed in environments with polarity intermediate between those of CH(2)Cl(2) and propan-2-ol, suggesting that the CyPLOS tentacles infiltrate the mid-polar region of the membranes.

Gold nanoparticles protected by fluorinated ligands for 19F MRI

Gold nanoparticles coated with fluorinated ligands (F-MPCs) present features suitable for (19)F MRI as observed from phantom experiments. Cellular uptake, by HeLa cells, and toxicity of fluorescent dye-decorated F-MPCs are presented together with their ability to bind hydrophobic molecules allowing for a potential combination of targeting, delivery and imaging features.

Gold nanoparticles as drug carriers: a contribution to the quest for basic principles for monolayer design

Two structurally different water-soluble homoligand gold nanoparticle systems, one featuring a rigid fluorous monolayer in the proximity of the gold core and the other featuring a flexible fluorinated region in a distal position, were studied as putative hosting systems by determining their binding constants for a series of fluorinated and non-fluorinated radical probes by means of ESR spectroscopy. Comparison of the binding constants obtained with hydrogenated homoligand nanoparticles of similar structure used as the reference evidenced that the binding of both hydrogenated and fluorinated guests is favoured in the presence of fluorinated nanoparticles. In addition, a flexible fluorinated monolayer acts as a better hosting system than the more rigid counterpart. In the latter case decreasing the size of the nanoparticles causes a small decrease of the binding affinities for both hydrogenated and fluorinated guests. The same nanoparticle systems were analysed for their ability to retard the phase transfer of a fluorescent dye from an aqueous solution to a toluene layer. All of the nanoparticles studied produced a significant decrease of the phase transfer rate of the dye because of the efficient interaction with the monolayer. These data support the introduction of fluorinated moieties in the monolayer of gold nanoparticles as a novel design tool for the development of drug delivery systems.

New meso-substituted trans-A2B2 di(4-pyridyl)porphyrins as building blocks for metal-mediated self-assembling of 4 + 4 Re(I)–porphyrin metallacycles

The reaction between 5-(4-pyridyl)dipyrrylmethane and aromatic aldehydes affords meso-arylsubstituted trans-A2B2 di(4-pyridyl)porphyrins which are key building blocks in the metal-mediated self-assembling of supramolecular structures. A careful optimization of the reaction conditions allowed us to obtain 5,15-diphenyl-10,20-di(4-pyridyl)porphyrin (P1), and two analogues bearing on the meso-phenyl substituents two dipropyl- (P4) or dihexyl-alkyl chains (P5), with yields ranging from 53 to 63%. Porphyrin P1 reacts with Re(CO5)Br to give the expected 4 + 4 Re(I)-porphyrin metallacycle which has been fully characterized by means of infrared, NMR and UV-Vis (absorption and emission) spectroscopies and by guest inclusion studies. Unexpectedly the addition of alkyl chains to the porphyrin fragment, which increase the solubility of the porphyrin in organic solvents, has the opposite effect on the adduct with Re(I). Indeed, the reaction between Re(CO5)Br and porphyrins P4,5 gives very insoluble materials, hampering their complete characterization.

Carbohydrate-based synthetic ion transporters.

In this work, carbohydrate-based systems designed as artificial ion transporters have been surveyed. Despite the large structural diversity and ease of manipulations of carbohydrates, in principle endowed with a variety of desirable properties for ionophoric activity, only few examples of sugar-containing compounds have been reported in the literature for these purposes. The most remarkable example is the family of modified β-cyclodextrins, resulting in active cation and/or anion transporters when long, flexible n-alkyl or oligo-ethylene or butylene glycol chains are appended at the lower rim of the macrocycle. Interesting features have been also found in amphiphilic CyPLOS (Cyclic Phosphate-Linked Oligosaccharide) dimers, that is macrocycles with two phenyl-β-D-glucopyranoside residues, 4,6-linked through phosphodiester bonds, derivatized with tetraethylene glycol tentacles. A wider repertoire of available carbohydrate-based scaffolds is expected to largely stimulate the discovery of novel, efficient artificial ionophores, of great interest for both technological and biomedical applications.

Self-sorting in mixed fluorinated/hydrogenated assemblies

Abstract Mixtures of fluorinated and hydrogenated compounds display peculiar properties arising from their mutual phobicity and the same applies to semifluorinated species in which a reciprocal phobicity pattern exists within the same molecule. The interest in assemblies comprising these species stems from the ease in which self-sorting can take place, allowing the preparation of compartmentalised molecular aggregates with unique hydrophobic patterns or surface features. Most importantly, this is the result of molecular properties rather than specifically designed fabrication techniques. This brief overview describes some examples that are instrumental to present the features of fluorinated/hydrogenated supramolecular assemblies in which self-sorting of the dislike units takes place at different length scales. This review is focussed on flat assemblies such as self-assembled monolayers on gold surfaces, Langmuir Blodgett films and on three dimensional assemblies such as micelles, vesicles and nanoparticles.