Magdalena Poplawska

THE ADDITION OF NITRILE OXIDES TO C60

Abstract The 1,3-dipolar cycloaddition of nitrile oxides to C60 is described. These reactions result in the formation of fullerene-fused isoxazoline heterocycles bearing a series of different substituents in 3-position. The preparation and spectroscopic characterization of these compounds are reported, as well as some investigations of the reactivity of these heterocycles. It is found that fullerene isoxazolines are less reactive than aliphatic isoxazolines.

Synthesis of hydrogenated fullerenes by zinc/acid reduction

Abstract Reduction of C 60 with zinc and acid results in the formation of C 60 H 2 , C 60 H 4 , and more highly hydrogenated fullerenes.

NEW METHOD OF IN SITU GENERATION OF NITRILE OXIDES BY MNO2 OXIDATION OF ALDOXIMES

Abstract Manganese(IV) oxide (MnO2) was found to oxidize aldoximes to nitrile oxides. Nitrile oxides were trapped in situ with dipolarophiles to furnish 2-oxazolines. The best results were obtained with hydroximinoacetates as nitrile oxide precursors.

Comparative cytotoxicity studies of carbon-encapsulated iron nanoparticles in murine glioma cells.

Carbon-encapsulated iron nanoparticles (CEINs) have recently emerged as a new class of magnetic nanomaterials with a great potential for an increasing number of biomedical applications. To address the current deficient knowledge of cellular responses due to CEIN exposures, we focused on the investigation of internalization profile and resulting cytotoxic effects of CEINs (0.0001-100 μg/ml) in murine glioma cells (GL261) in vitro. The studied CEIN samples were characterized (TEM, FT-IR, Zeta potential, Boehm titration) and examined as raw and purified nanomaterials with various surface chemistry composition. Of the four type CEINs (the mean diameter 47-56 nm) studied here, the as-synthesized raw nanoparticles (Fe@C/Fe) exhibited high cytotoxic effects on the plasma cell membrane (LDH, Calcein AM/PI) and mitochondria (MTT, JC-1) causing some pro-apoptotic evens (Annexin V/PI) in glioma cells. The effects of the purified (Fe@C) and surface-modified (Fe@C-COOH and Fe@C-(CH2)2COOH) CEINs were found in quite similar patterns; however, most of these cytotoxic events were slightly diminished compared to those induced by Fe@C/Fe. The study showed that the surface-functionalized CEINs affected the cell cycle progression in both S and G2/M phases to a greater extent compared to that of the rest of nanoparticles studied to data. Taken all together, the present results highlight the importance of the rational design of CEINs as their physicochemical features such as morphology, hydrodynamic size, impurity profiles, and especially surface characteristics are critical determinants of different cytotoxic responses.

Assessing carbon-encapsulated iron nanoparticles cytotoxicity in Lewis lung carcinoma cells

Carbon‐encapsulated iron nanoparticles (CEINs) have been considered as attractive candidates for several biomedical applications. In the present study, we synthesized CEINs (the mean diameter 40–80 nm) using a carbon arc route, and the as‐synthesized CEINs were characterized (scanning and transmission electron microscopy, dynamic light scattering, turbidimetry, Zeta potential) and further tested as raw and purified nanomaterials containing the carbon surface modified with acidic groups. For cytotoxicity evaluation, we applied a battery of different methods (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide, lactate dehydrogenase, calcein AM/propidium iodide, annexin V/propidium iodide, JC‐1, cell cycle assay, Zeta potential, TEM and inductively coupled plasma mass spectrometry) to address the strategic cytotoxic endpoints of Lewis lung carcinoma cells due to CEIN (0.0001–100 µg ml–1) exposures in vitro. Our studies evidence that incubation of Lewis lung carcinoma cells with CEINs is accompanied in substantial changes of zeta potential in cells and these effects may result in different internalization profiles. The results show that CEINs increased the mitochondrial and cell membrane cytotoxicity; however, the raw CEIN material (Fe@C/Fe) produced higher toxicities than the rest of the CEINs studied to data. The study showed that non‐modified CEINs (Fe@C/Fe and Fe@C) elevated some pro‐apoptotic events to a greater extent compared to that of the surface‐modified CEINs (Fe@C‐COOH and Fe@C‐(CH2)2COOH). They also diminished the mitochondrial membrane potentials. In contrast to non‐modified CEINs, the surface‐functionalized nanoparticles caused the concentration‐ and time‐dependent arrest of the S phase in cells. Taken all together, our results shed new light on the rational design of CEINs, as their geometry, hydrodynamic and, in particular, surface characteristics are important features in selecting CEINs as future nanomaterials for nanomedicine applications. Copyright

Conjugation of polyethylenimine and its derivatives to carbon-encapsulated iron nanoparticles

Carbon-based nanomaterials functionalized by cationic polymers are interesting starting materials for the development of nanotheranostic systems. In this study, polyethylenimine (PEI) and its pre-synthesized derivatives were conjugated to carbon-encapsulated iron nanoparticles (CEINs). Branched PEIs of various molecular weight were derivatized. The aim of the polymer modification was to introduce carboxylic functionality to the PEI structure. Two different synthetic pathways were proposed: the amide-type reaction with succinic acid anhydride and reductive amination using p-formylbenzoic acid. The polyethylenimine derivatives were analyzed by means of spectroscopic methods (NMR and FT-IR). In order to determine the ratio of primary, secondary and tertiary amine groups in the modified polymers, inverted-gate 13C NMR spectroscopy was applied. Next, CEINs modified with two different surface carboxylic linkers were functionalized using pristine PEI and its derivatives. The conjugation of the polymer to the surface-modified nanoparticles was carried out using the carbodiimide–amine type reaction. The success of the conjugation process was confirmed by thermogravimetry and infrared spectroscopy. The morphological details were analyzed using transmission electron microscopy, whilst the surface zeta potential and the average particle size were determined by dynamic light scattering. It was found that the molecular weight of the polymer and the type of the surface linker were the key factors which crucially influenced the functionalization yield and the physicochemical features of the synthesized nanoplatforms. The best dispersion stability in aqueous media and the smallest mean hydrodynamic particle size was found for CEINs with the longer carboxylic linker.

Grinding-induced functionalization of carbon-encapsulated iron nanoparticles

Covalent functionalization of carbon-encapsulated iron nanoparticles based on the grinding-induced 1,3-cycloaddition reaction of nitrile oxides is presented. We report an easy to perform, fast and efficient method for the direct introduction of various types of functional moieties, such as carboxylic, metallocene and sugar units, into carbon-encapsulated iron nanoparticles.

Sulfhydrylated graphene-encapsulated iron nanoparticles directly aminated with polyethylenimine: a novel magnetic nanoplatform for bioconjugation of gamma globulins and polyclonal antibodies

This study presents for the first time the direct amination of graphene-encapsulated iron nanoparticles (GEINs) with polyethylenimine (PEI) via radical-type reaction. This work describes the first example of a direct addition of N-centered radical species onto the graphene layer. The pristine PEI and the PEI attached to GEINs have also been derivatized to introduce sulfhydryl functionalities. The proposed two-step protocol constitutes a novel, versatile and low cost method for the synthesis of polymer derivatives decorated with SH moieties. The derivatives of pristine polyethylenimine were analyzed by means of spectroscopic methods (NMR and IR), while the obtained carbon materials were studied by thermogravimetry, infrared spectroscopy, dynamic light scattering, and transmission electron microscopy. Finally, the concomitant part of this work focused on the bioconjugation type reactions of various biocompounds, including bovine gamma-globulins and human polyclonal antibodies of class IgG, with the as-obtained sulfhydrylated GEINs-PEI nanoplatform. The presence of immobilized molecules was confirmed by thermogravimetry, protein and fluorescence assays as well as confocal microscopy images.

Nanoconjugates of ferrocene and carbon-encapsulated iron nanoparticles as sensing platforms for voltammetric determination of ceruloplasmin in blood

The nanoparticles comprising of iron core and carbon shell were decorated with ferrocene derivatives: ferrocenecarboxaldehyde (Fc-1) and ferrocenecarboxaldehyde oxime (Fc-2). A microdrop of suspension of the nanoconjugate was placed on a glassy-carbon electrode to prepare the recognition/sensing layer. Drying and purification of the sensing layer resulted in a well-defined and stable square-wave voltammogram of the ferrocene moiety. The height of the voltammetric peak increased in the presence of ceruloplasmin. That increase was linearly dependent on the logarithmic concentration of ceruloplasmin in blood. The applied external magnetic field was a factor which yielded better sensitivity and repeatability of the sensor response. The linearity of sensor response was found to be between 0.001 and 10μgdL-1 and 0.05-10μgdL-1 for both nanoconjugates: Fe@C-Fc-1 and Fe@C-Fc-2, in the presence and absence of the magnet, respectively. The obtained detection limit (LOD) for Fe@C-Fc-1 was found to be 0.60 and 0.10μgdL-1 in the absence and presence of magnetic field, respectively, whilst for Fe@C-Fc-2 was 0.4 and 0.07μgdL-1 in the absence and presence of a magnet, respectively. The proposed method is selective because the presence of common antioxidants in blood did not interfere significantly with the determination of the concentration of ceruloplasmin.

Novel non-covalent stable supramolecular ternary system comprising of cyclodextrin and branched polyethylenimine

The synthesis of a novel supramolecular system comprising of branched polyethylenimine and cyclodextrin, is presented. The synthesis route is based on the self-assembly phenomena with the inclusion of solvent molecules. The systems are formed by a hydrogen-bonding network and host–guest type interactions between the building blocks. It was found that the native cyclodextrin and polyethylenimine are able to form stable systems when the reaction medium constitutes a polar solvent forming host–guest type complexes with cyclodextrin. A special consideration was paid on the detailed spectroscopic analyses of the obtained water-soluble constructs, including ROESY and diffusion-ordered (DOSY) NMR spectroscopy studies. The versatility and significance of DOSY technique for the analysis of the cyclodextrin complexes and its non-covalent systems with branched polymers, were presented. It was also found that the guest molecules that were incorporated in the complexes exhibited enhanced thermal stability. The morphological details in the solid state were obtained by scanning electron microscope.Graphical Abstract