Federica Aiello

Gli1/DNA interaction is a druggable target for Hedgehog‐dependent tumors

Hedgehog signaling is essential for tissue development and stemness, and its deregulation has been observed in many tumors. Aberrant activation of Hedgehog signaling is the result of genetic mutations of pathway components or other Smo‐dependent or independent mechanisms, all triggering the downstream effector Gli1. For this reason, understanding the poorly elucidated mechanism of Gli1‐mediated transcription allows to identify novel molecules blocking the pathway at a downstream level, representing a critical goal in tumor biology. Here, we clarify the structural requirements of the pathway effector Gli1 for binding to DNA and identify Glabrescione B as the first small molecule binding to Gli1 zinc finger and impairing Gli1 activity by interfering with its interaction with DNA. Remarkably, as a consequence of its robust inhibitory effect on Gli1 activity, Glabrescione B inhibited the growth of Hedgehog‐dependent tumor cells in vitro and in vivo as well as the self‐renewal ability and clonogenicity of tumor‐derived stem cells. The identification of the structural requirements of Gli1/DNA interaction highlights their relevance for pharmacologic interference of Gli signaling.

Multiscale morphology design of hybrid halide perovskites through a polymeric template

Hybrid halide perovskites have emerged as promising active constituents of next generation solution processable optoelectronic devices. During their assembling process, perovskite components undergo very complex dynamic equilibria starting in solution and progressing throughout film formation. Finding a methodology to control and affect these equilibria, responsible for the unique morphological diversity observed in perovskite films, constitutes a fundamental step towards a reproducible material processability. Here we propose the exploitation of polymer matrices as cooperative assembling components of novel perovskite CH3NH3PbI3 : polymer composites, in which the control of the chemical interactions in solution allows a predictable tuning of the final film morphology. We reveal that the nature of the interactions between perovskite precursors and polymer functional groups, probed by Nuclear Magnetic Resonance (NMR) spectroscopy and Dynamic Light Scattering (DLS) techniques, allows the control of aggregates in solution whose characteristics are strictly maintained in the solid film, and permits the formation of nanostructures that are inaccessible to conventional perovskite depositions. These results demonstrate how the fundamental chemistry of perovskite precursors in solution has a paramount influence on controlling and monitoring the final morphology of CH3NH3PbI3 (MAPbI3) thin films, foreseeing the possibility of designing perovskite : polymer composites targeting diverse optoelectronic applications.

Mucoadhesivity and release properties of quaternary ammonium–chitosan conjugates and their nanoparticulate supramolecular aggregates: An NMR investigation

Selective relaxation rate measurements effectively proved the affinity of dexamethasone 21-phosphate disodium salt for quaternary ammonium-chitosan conjugates, their thiolated derivatives and the corresponding nanostructured aggregates. Affinity was also probed by dynamic dialysis. The release profile of dexamethasone loaded nanoparticles was defined by quantitative NMR and interrupted dialysis experiments, and mucoadhesivity of empty nanoparticles was effectively probed by selective relaxation rate measurements.

Synergistic effects of trace amounts of water in the enantiodiscrimination processes by lipodex E: a spectroscopic and computational investigation.

Nuclear magnetic resonance (NMR) investigations on mixtures containing octakis(3-O-butanoyl-2,6-di-O-pentyl)-γ-cyclodextrin (Lipodex E) and each enantiomer of methyl-2-chloropropionate (MCP) ascertained the role of trace amounts of water in the enantiodiscrimination processes. Water is deeply included into the cyclodextrin and favors the formation of the inclusion complex with (S)-MCP, whereas (R)-MCP is only slightly affected, thus causing a significant increase of NMR differentiation. Molecular dynamics simulations were performed to shed light on the possible behavior of Lipodex E in different conditions (i.e., solvent, inclusion complexes), providing energetic and atomistic details that are in agreement with NMR observations.

Water soluble heptakis(6-deoxy-6-thio)cyclomaltoheptaose capped gold nanoparticles via metal vapour synthesis: NMR structural characterization and complexation properties.

The complexation of heptakis(6-deoxy-6-thio)cyclomaltoheptaose to gold nanoparticles prepared by using the Metal Vapour Synthesis (MVS) led to water soluble gold nanoaggregates, thermally stable at 25°C. The role of gold concentration in the MVS-derived starting solution as well as of the cyclodextrin to gold molar ratio on the size of cyclodextrin-capped gold nanoparticles were investigated. The ability of cyclodextrin bonded to gold nanoparticles to include deoxycytidine was also probed in comparison with that of 1-thio-β-D-glucose sodium salt.

Monomeric and Dimeric 9-O Anthraquinone and Phenanthryl Derivatives of Cinchona Alkaloids as Chiral Solvating Agents for the NMR Enantiodiscrimination of Chiral Hemiesters†

Mono- and bis-alkaloid chiral auxiliaries with anthraquinone or phenanthryl cores were probed as chiral solvating agents (CSAs) for the enantiodiscrimination of chiral cyclic hemiesters. The dimeric anthraquinone derivative and the monomeric phenanthryl one showed remarkable efficiency in the nuclear magnetic resonance (NMR) differentiation of enantiomeric mixtures of hemiesters. An anthraquinone analogous with a single alkaloid unit was remarkably less effective. The conformational prevalence of the chiral auxiliaries were ascertained by NMR.

Cyclodextrins as inhibitors of the precipitation of riboflavin-5’-phosphate due to presence of zinc chloride: A NMR investigation

HIGHLIGHTSRiboflavin‐5’‐phosphate precipitates in the presence of divalent cations.Cyclodextrins were probed as solubilizing agents for riboflavin‐5’‐phosphate.&bgr;‐cyclodextrin is the best solubilizing agent.A 1 to 2 riboflavin‐5’‐phosphate/&bgr;‐cyclodextrin complex is formed in solution. ABSTRACT Several cyclodextrins (CDs) were probed in order to counteract the precipitation of riboflavin‐5’‐phosphate (or flavin mononucleotide, FMN‐P) due to the presence of divalent cations, by exploiting Nuclear Magnetic Resonance (NMR) spectroscopy both for quantitative analyses and stereochemical characterizations. Among CDs, &bgr;‐cyclodextrin (&bgr;‐CD) showed the best solubilizing power in virtue of the formation of a 1–2 FMN‐P/&bgr;‐CD complex, the stereochemistry of which was ascertained by ROESY (Rotating‐frame Overhauser Enhanced SpectroscopY) measurements.

Covalently assembled resorcin[4]arenes and molecular tweezers: a chiral recognition rationale by NMR

Abstract Chiral diamides and tetramidic resorcin[4]arenes deriving from (R,R)-1,2-diaminocyclohexane and (S,S)-1,2-diphenylethylendiamine, and a valine containing resorcin[4]arene have been compared by NMR in the enantiodiscrimination of mandelic acid. The relevance of cooperation between side arms and external surface of resorcin[4]arene core has been ascertained.

Chiral Analysis by NMR Spectroscopy: Chiral Solvating Agents

Abstract This chapter will focus on the use of chiral solvating agents (CSAs) for the detection and quantification of enantiomeric substrates by nuclear magnetic resonance spectroscopy, with the aim of identifying the trend of the researches on this topic in this last decade. The main classes of CSAs will be described, spanning from low-to-medium-sized CSAs to structurally complex systems with highly preorganized structures. CSA features will be outlined by means of several examples, which are not meant to cover all the literature on each of the topics.

Role of nanostructured aggregation of chitosan derivatives on [5-methionine]enkephalin affinity

Affinities of quaternary ammonium-chitosan conjugates, their thiolated derivatives and corresponding nanostructured aggregates towards the hydrophilic drug [5-methionine]enkephalin were compared by Nuclear Magnetic Resonance (NMR) spectroscopic methods based on proton selective relaxation rate measurements. Nanoaggregates showed enhanced drug affinity in comparison with corresponding polymers, especially in the case of thiolated systems.