Alessandro Ponti

Cu/Cu-oxide nanoparticles as catalyst in the “click” azide–alkyne cycloaddition

Mixed Cu/Cu-oxide nanoparticles are an effective catalyst for the “click” 1,3-dipolar cycloaddition between azides and terminal alkynes, featuring short reaction times, soft reaction conditions and full regioselectivity.

A Smart Platform for Hyperthermia Application in Cancer Treatment: Cobalt-Doped Ferrite Nanoparticles Mineralized in Human Ferritin Cages

Magnetic nanoparticles, MNPs, mineralized within a human ferritin protein cage, HFt, can represent an appealing platform to realize smart therapeutic agents for cancer treatment by drug delivery and magnetic fluid hyperthermia, MFH. However, the constraint imposed by the inner diameter of the protein shell (ca. 8 nm) prevents its use as heat mediator in MFH when the MNPs comprise pure iron oxide. In this contribution, we demonstrate how this limitation can be overcome through the controlled doping of the core with small amount of Co(II). Highly monodisperse doped iron oxide NPs with average size of 7 nm are mineralized inside a genetically modified variant of HFt, carrying several copies of α-melanocyte-stimulating hormone peptide, which has already been demonstrated to have excellent targeting properties toward melanoma cells. HFt is also conjugated to poly(ethylene glycol) molecules to increase its in vivo stability. The investigation of hyperthermic properties of HFt-NPs shows that a Co doping of 5% is enough to strongly enhance the magnetic anisotropy and thus the hyperthermic efficiency with respect to the undoped sample. In vitro tests performed on B16 melanoma cell line demonstrate a strong reduction of the cell viability after treatment with Co doped HFt-NPs and exposure to the alternating magnetic field. Clear indications of an advanced stage of apoptotic process is also observed from immunocytochemistry analysis. The obtained data suggest this system represents a promising candidate for the development of a protein-based theranostic nanoplatform.

One-step synthesis and functionalization of hydroxyl-decorated magnetite nanoparticles.

Magnetite nanoparticles covered by a layer of omega-hydroxycarboxylic acid were synthesized in one step by high-temperature decomposition of iron(III) omega-hydroxycarboxylates in tri- and tetra-ethylene glycol. The nanoparticles were characterized by TEM, XRD, IR, XPS and NMR techniques in order to show that they comprise a crystalline magnetite core and actually bear on the outer surface terminal hydroxy groups. The latter ones are convenient handles for further functionalization as opposed to the chemically-inert aliphatic chains which cover conventionally synthesized nanoparticles. This was shown by several examples in which the hydroxy groups on the nanoparticle surface were easily transformed in other functional groups or reacted with other molecules. For instance, the hydroxyl-decorated nanoparticles were made water soluble by esterification with a PEGylated acetic acid. The reactive behavior of the surfactant monolayer was monitored by degrading the nanoparticles with aqueous acid and isolating the surfactant for NMR characterization. In general, the reactivity of the terminal hydroxyl groups on the nanoparticle surface parallels that observed in the free surfactants. The reported hydroxyl-decorated magnetite nanoparticles can be thus considered as pro-functional nanoparticles, i.e., a convenient starting material to functionalized magnetic nanoparticles.

Uncommon aqueous media for nitrilimine cycloadditions. I. Synthetic and mechanistic aspects in the formation of 1-aryl-5-substituted-4,5-dihydropyrazoles

A number of 1-aryl-5-substituted-4,5-dihydropyrazoles 4 have been synthesised by 1,3-dipolar cycloaddition of variously substituted nitrilimines 2 onto the appropriate alkenyl dipolarophiles 3 in aqueous media and in the presence of a surfactant. Under these conditions, uncommon for the large majority of [3u2006+u20062] cycloadditions, the electronic features of both the cycloaddends strongly dictate the reaction outcome. Clean and fast cycloadditions were observed between electron-rich nitrilimines and electron-poor dipolarophiles, while the reversal of the electronic features of the reactants gave poor results. Changes in surfactant concentration leads to some novel mechanistic insights.

Picosecond solvation dynamics of alkali cations in superfluid 4He nanodroplets

Infrared spectra are reported for carbon dioxide and nitrous oxide solvated in superfluid helium droplets, corresponding to the vibrational excitation of the (0201)/(1001) Fermi diad. Although the rotational constants of these two molecules are similar in the gas phase, they are observed to be quite different in liquid helium, namely, 0.154 cm−1 for CO2 and 0.0717 cm−1 for N2O. In addition, solvation in helium results in shifts in the vibrational origin that are in the opposite directions, −0.42 cm−1, for CO2 and +1.2 cm−1 for N2O. The spectra also show strong droplet size dependence, indicative of the interactions between the molecule and the liquid.

Stereoselective intramolecular cycloadditions of homochiral nitrile imines: synthesis of enantiomerically pure 3,3a-dihydro-pyrazolo[1,5-a][1,4]benzodiazepine-6(4H)-ones

Abstract Starting from the commercially available ( S )-1-phenylethylamine, we have synthesised the homochiral hydrazonoyl chlorides 4 . The intramolecular cycloaddition of the corresponding nitrile imines 5 gave the diastereoisomeric 3,3a-dihydro-pyrazolo[1,5- a ][1,4]benzodiazepine-6(4 H )-ones 6 and 7 in enantiopure form.

Chirality in the Absence of Rigid Stereogenic Elements: The Absolute Configuration of Residual Enantiomers of C3-Symmetric Propellers

Two new tris(aryl)phosphane oxides existing as configurationally stable residual enantiomers have been synthesised and their racemates resolved by semipreparative HPLC on a chiral stationary phase (CSP HPLC). One of them, recognised as a conglomerate, could be resolved by fractional crystallisation at a preparative scale level. In this case, the absolute configuration of the propeller-shaped molecule was determined by anomalous X-ray scattering. The problem of the correlative assignment of the absolute configuration to all known C(3)-symmetric three-bladed propeller-shaped molecules existing as stable residual enantiomers is discussed. The configurational stability of the new chiral phosphane oxides and of the corresponding phosphanes was evaluated by CD signal decay kinetics and dynamic (1)H NMR spectroscopy. The racemisation barriers in phosphanes were found about 10 kcal mol(-1) lower than those found for the corresponding oxides, though geometry and inter-ring gearing would be very similar in the two series. Configurational stability of residual tris(aryl)phosphanes was found to be influenced by the electronic availability of the phosphorus centre, as evaluated by electrochemical CV experiments.

Assessment of mechanistic hypotheses of 1,3-dipolar cycloaddition of (arylsulfonyl)allene to nitrilimines by DFT reactivity indices

The mechanism of 1,3-dipolar cycloaddition between 1-[2-(acetylamino)phenylsulfonyl]-1,2-propadiene 1 and a series of N-(4-substituted)phenyl-C-methoxycarbonylnitrilimines 2 has been reinvestigated on the basis of DFT calculations and a quantitative formulation of the HSAB principle. Comparison of the new computational results with experimental findings led to the formulation of a mechanistic scheme involving both 1,3-prototropic and 1,3-arylsulfonyl shifts. The role of silver cation is also pointed out.

Poly(amidoamine)s carrying TEMPO residues for NMR imaging applications

An amphoteric bio-compatible and stealth-like poly (amidoamine) named ISA23 was obtained from 2,2-bis(acrylamido)acetic acid (BAC) and 2-methylpiperazine. The partial substitution of 4-amino-2,2,6,6-tetramethylpiperidin-1-oxyl (Amino-TEMPO) for 2-methylpiperazine as co-monomer gave two new PAA-TEMPO conjugates based on ISA23: ISA23-TEMPO1 and ISA23-TEMPO2 with 10 and 40% TEMPO-carrying units per polymer chain, respectively. In this study, a thorough NMR characterization of ISA23 polymer together with NMR and ESR characterizations of the ISA23-TEMPO derivatives and a preliminary evaluation of their potential as NMR labels for imaging applications are reported. Relaxivity measurements performed on ISA23-TEMPO1 and ISA23-TEMPO2 showed relaxivities of 0.4 and 1.8 mM−1 s−1, respectively, indicating that the PAA-TEMPO adducts have a definite potential as NMR imaging contrast agents. This was confirmed by preliminary magnetic resonance imaging (MRI) determinations.

Uncommon aqueous media for nitrilimine cycloadditions. II. Computational study of the effect of water on reaction rate

The effect of water on the 1,3-dipolar cycloaddition reaction of nitrilimines to alkenes has been studied by HF and DFT ab initio calculations. As solvation models we used the polarizable continuum model and a model comprising small clusters consisting of reactants hydrogen-bonded to water molecules. In addition, a combination of these two models was considered. Reactivity has been qualitatively estimated by the familiar frontier molecular orbital approach and quantitatively computed by a recent extension to the hard–soft acid–base principle involving molecular reactivity indices. The main conclusions drawn from the extensive computational results are that (i) the effect of water is in general rather small and (ii) therefore, water is not directly responsible for the large acceleration of the 1,3-dipolar cycloaddition reaction of nitrilimines to alkenes. Its role is surely minor with respect to that played by the ionic catalysts present in the reaction mixture, in agreement with the conclusions drawn in the experimental companion paper.