The Potent Oxidant Anticancer Activity of Organoiridium Catalysts

Platinum complexes are the most widely used anticancer drugs; however, new generations of agents are needed. The organoiridium(III) complex [(η⁵‐Cp^xbiph)Ir(phpy)(Cl)] ( 1‐Cl ), which contains π‐bonded biphenyltetramethylcyclopentadienyl (Cp^xbiph) and C^N‐chelated phenylpyridine (phpy) ligands, undergoes rapid hydrolysis of the chlorido ligand. In contrast, the pyridine complex [(η⁵‐Cp^xbiph)Ir(phpy)(py)]⁺ ( 1‐py ) aquates slowly, and is more potent (in nanomolar amounts) than both 1‐Cl and cisplatin towards a wide range of cancer cells. The pyridine ligand protects 1‐py from rapid reaction with intracellular glutathione. The high potency of 1‐py correlates with its ability to increase substantially the level of reactive oxygen species (ROS) in cancer cells. The unprecedented ability of these iridium complexes to generate H₂O₂ by catalytic hydride transfer from the coenzyme NADH to oxygen is demonstrated. Such organoiridium complexes are promising as a new generation of anticancer drugs for effective oxidant therapy.     

Selective Formation of Metastable Ferrihydrite in the Chiton Tooth

Metastable precursors are thought to play a major role in the ability of organisms to create mineralized tissues. Of particular interest are the hard and abrasion‐resistant teeth formed by chitons, a class of rock‐grazing mollusks. The formation of chiton teeth relies on the precipitation of metastable ferrihydrite (Fh) in an organic scaffold as a precursor to magnetite. In vitro synthesis of Fh under physiological conditions has been challenging. Using a combination of X‐ray absorption and electron paramagnetic resonance spectroscopy, we show that, prior to Fh formation in the chiton tooth, iron ions are complexed by the organic matrix. In vitro experiments demonstrate that such complexes facilitate the formation of Fh under physiological conditions. These results indicate that acidic molecules may be integral to controlling Fh formation in the chiton tooth. This biological approach to polymorph selection is not limited to specialized proteins and can be expropriated using simple chemistry.     

Supramolecular Architectures from Bent‐Core Dendritic Molecules

Control of the self‐assembly of small molecules to generate architectures with diverse shapes and dimensions is a challenging research field. We report unprecedented results on the ability of ionic, bent dendritic molecules to aggregate in water. A range of analytical techniques (TEM, SEM, SAED, and XRD) provide evidence of the formation of rods, spheres, fibers, helical ribbons, or tubules from achiral molecules. The compact packing of the bent‐core structures, which promotes the bent‐core mesophases, also occurs in the presence of a poor solvent to provide products ranging from single objects to supramolecular gels. The subtle balance of molecule/solvent interactions and appropriate molecular designs also allows the transfer of molecular conformational chirality to morphological chirality in the overall superstructure. Functional motifs and controlled morphologies can be combined, thereby opening up new prospects for the generation of nanostructured materials through a bottom‐up strategy.     

Gold(III) π-Allyl Complexes

Gold(III) π-complexes have been authenticated recently with alkenes, alkynes, and arenes. The key importance of Pd^II π-allyl complexes in organometallic chemistry (Tsuji–Trost reaction) prompted us to explore gold(III) π-allyl complexes, which have remained elusive so far. The (P,C)Au^III(allyl) and (methallyl) complexes 3 and 3′ were readily prepared and isolated as thermally and air-stable solids. Spectroscopic and crystallographic analyses combined with detailed DFT calculations support tight quasi-symmetric η³-coordination of the allyl moiety. The π-allyl gold(III) complexes are activated towards nucleophilic additions, as substantiated with β-diketo enolates.     

Evidence for Electron Transfer between Graphene and Non-Covalently Bound π-Systems

Hybridizing graphene and molecules possess a high potential for developing materials for new applications. However, new methods to characterize such hybrids must be developed. Herein, the wet-chemical non-covalent functionalization of graphene with cationic π-systems is presented and the interaction between graphene and the molecules is characterized in detail. A series of tricationic benzimidazolium salts with various steric demand and counterions was synthesized, characterized and used for the fabrication of graphene hybrids. Subsequently, the doping effects were studied. The molecules are adsorbed onto graphene and studied by Raman spectroscopy, XPS as well as ToF-SIMS. The charged π-systems show a p-doping effect on the underlying graphene. Consequently, the tricationic molecules are reduced through a partial electron transfer process from graphene, a process which is accompanied by the loss of counterions. DFT calculations support this hypothesis and the strong p-doping could be confirmed in fabricated monolayer graphene/hybrid FET devices. The results are the basis to develop sensor applications, which are based on analyte/molecule interactions and effects on doping.     

Treatment of Human Glioblastoma U251 Cells with Sulforaphane and a Peptide Nucleic Acid (PNA) Targeting miR-15b-5p: Synergistic Effects on Induction of Apoptosis

Glioblastoma multiforme (GBM) is a lethal malignant tumor accounting for 42% of the tumors of the central nervous system, the median survival being 15 months. At present, no curative treatment is available for GBM and new drugs and therapeutic protocols are urgently needed. In this context, combined therapy appears to be a very interesting approach. The isothiocyanate sulforaphane (SFN) has been previously shown to induce apoptosis and inhibit the growth and invasion of GBM cells. On the other hand, the microRNA miR-15b is involved in invasiveness and proliferation in GBM and its inhibition is associated with the induction of apoptosis. On the basis of these observations, the objective of the present study was to determine whether a combined treatment using SFN and a peptide nucleic acid interfering with miR-15b-5p (PNA-a15b) might be proposed for increasing the pro-apoptotic effects of the single agents. To verify this hypothesis, we have treated GMB U251 cells with SFN alone, PNA-a15b alone or their combination. The cell viability, apoptosis and combination index were, respectively, analyzed by calcein staining, annexin-V and caspase-3/7 assays, and RT-qPCR for genes involved in apoptosis. The efficacy of the PNA-a15b determined the miR-15b-5p content analyzed by RT-qPCR. The results obtained indicate that SFN and PNA-a15b synergistically act in inducing the apoptosis of U251 cells. Therefore, the PNA-a15b might be proposed in a “combo-therapy” associated with SFN. Overall, this study suggests the feasibility of using combined treatments based on PNAs targeting miRNA involved in GBM and nutraceuticals able to stimulate apoptosis.     

Glucose/Ribitol Dehydrogenase and 16.9 kDa Class I Heat Shock Protein 1 as Novel Wheat Allergens in Baker’s Respiratory Allergy

Wheat allergens are responsible for symptoms in 60–70% of bakers with work-related allergy, and knowledge, at the molecular level, of this disorder is progressively accumulating. The aim of the present study is to investigate the panel of wheat IgE positivity in allergic Italian bakers, evaluating a possible contribution of novel wheat allergens included in the water/salt soluble fraction. The water/salt-soluble wheat flour proteins from the Italian wheat cultivar Bolero were separated by using 1-DE and 2-DE gel electrophoresis. IgE-binding proteins were detected using the pooled sera of 26 wheat allergic bakers by immunoblotting and directly recognized in Coomassie stained gel. After a preparative electrophoretic step, two enriched fractions were furtherly separated in 2-DE allowing for detection, by Coomassie, of three different proteins in the range of 21–27 kDa that were recognized by the pooled baker’s IgE. Recovered spots were analyzed by nanoHPLC Chip tandem mass spectrometry (MS/MS). The immunodetected spots in 2D were subjected to mass spectrometry (MS) analysis identifying two new allergenic proteins: a glucose/ribitol dehydrogenase and a 16.9 kDa class I heat shock protein 1. Mass spectrometer testing of flour proteins of the wheat cultivars utilized by allergic bakers improves the identification of until now unknown occupational wheat allergens.     

A Ferrofluid with Surface Modified Nanoparticles for Magnetic Hyperthermia and High ROS Production

A ferrofluid with 1,2-Benzenediol-coated iron oxide nanoparticles was synthesized and physicochemically analyzed. This colloidal system was prepared following the typical co-precipitation method, and superparamagnetic nanoparticles of 13.5 nm average diameter, 34 emu/g of magnetic saturation, and 285 K of blocking temperature were obtained. Additionally, the zeta potential showed a suitable colloidal stability for cancer therapy assays and the magneto-calorimetric trails determined a high power absorption density. In addition, the oxidative capability of the ferrofluid was corroborated by performing the Fenton reaction with methylene blue (MB) dissolved in water, where the ferrofluid was suitable for producing reactive oxygen species (ROS), and surprisingly a strong degradation of MB was also observed when it was combined with H₂O₂. The intracellular ROS production was qualitatively corroborated using the HT-29 human cell line, by detecting the fluorescent rise induced in 2,7-dichlorofluorescein diacetate. In other experiments, cell metabolic activity was measured, and no toxicity was observed, even with concentrations of up to 4 mg/mL of magnetic nanoparticles (MNPs). When the cells were treated with magnetic hyperthermia, 80% of cells were dead at 43 °C using 3 mg/mL of MNPs and applying a magnetic field of 530 kHz with 20 kA/m amplitude.