86 pubblicazioni classificate nel seguente modo:

Locking up G-Quadruplexes with Light-Triggered Staples Leads to Increased Topological, Thermodynamic, and Metabolic Stability
ANGEWANDTE CHEMIE. INTERNATIONAL EDITION
Autore/i: Barr, Jack; Cadoni, Enrico; Schellinck, Sofie; Laudadio, Emiliano; Martins, José C; Madder, Annemieke
Classificazione: 1 Contributo su Rivista
Abstract: G-quadruplexes (G4 s) are secondary, tetraplexed DNA structures abundant in non-coding regions of the genome, implicated in gene transcription processes and currently firmly recognised as important potential therapeutic targets. Given their affinity for human proteins, G4 structures are investigated as potential decoys and aptamers. However, G4 s tend to adopt different conformations depending on the exact environmental conditions, and often only one displays the specifically desired biological activity. Their less intensively studied counterparts, the elusive tetraplexed intercalated-motifs (IMs) are typically unstable at neutral pH, hampering the investigation of their potential involvement in a biological context. We herein report on a photochemical method for “stapling” such tetraplexed-structures, to increase their stability, lock their topology and enhance their enzymatic resistance, while maintaining biological activity. The chemical structure and topology of the stapled Thrombin Binding Aptamer (TBA) was spectroscopically characterised and rationalised in silico. The method was then extended to other biologically relevant G4- and IM-prone sequences, hinting towards potential application of such stapled structures in a therapeutic context.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/338393

Probing conformational dynamics of EGFR mutants via SEIRA spectroscopy: potential implications for tyrosine kinase inhibitor design
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
Autore/i: Laudadio, Emiliano; Piccirilli, Federica; Vondracek, Henrick; Mobbili, Giovanna; Semrau, Marta S.; Storici, Paola; Galeazzi, Roberta; Romagnoli, Elena; Sorci, Leonardo; Toma, Andrea; Aglieri, Vincenzo; Birarda, Giovanni; Minnelli, Cristina
Classificazione: 1 Contributo su Rivista
Abstract: Missense mutations in EGFR's catalytic domain alter its function, promoting cancer. SEIRA spectroscopy, supported by MD simulations, reveals structural differences in the compactness and hydration of helical motifs between active and inactive EGFR conformations models. These findings provide novel insights into the biophysical mechanisms driving EGFR activation and drug resistance, offering a robust method for studying emerging EGFR mutations and their structural impacts on TKIs’ efficacy.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/334252

Demonstration of Microwave Harvesting Through Pyroelectricity in Cryogenic Conditions: A Quantum-to-Experimental Approach
IEEE MICROWAVE AND WIRELESS TECHNOLOGY LETTERS
Autore/i: Aldrigo, Martino; Dragoman, Mircea; Dinescu, Adrian; Vasilache, Dan; Iordanescu, Sergiu; Dinu, Livia Alexandra; Dragoman, Daniela; Laudadio, Emiliano; Pavoni, Eleonora; Pierantoni, Luca; Mencarelli, Davide
Classificazione: 1 Contributo su Rivista
Abstract: In this letter, we present a comprehensive study of a planar field effect transistor (FET) with a graphene/ferroelectric channel on high-resistivity silicon substrate, able to convert the incident microwave power into a pyroelectric voltage in cryogenic conditions down to 100 K. The FET is based on a graphene monolayer/zirconium-doped hafnium oxide (HZO) heterostructure, being the graphene perforated with a matrix of nanoholes. This choice has two aims: 1) to create a bandgap in the graphene monolayer and 2) to reduce graphene's thermal conductivity, thereby promoting the generation of a pyroelectric current. Starting from quantum simulations to assess the electrical behavior of the channel, we measured in a cryogenic setup a maximum detected pyroelectric voltage of about 18 mV at 2 GHz and at 100 K. Moreover, the detected transient pulses fit in to solitons, which are typical for thin film ferroelectrics.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/340992

Towards graphene-based asymmetric diodes: a density functional tight-binding study
NANOSCALE ADVANCES
Autore/i: Mohebbi, Elaheh; Pavoni, Eleonora; Pierantoni, Luca; Stipa, Pierluigi; Hemmetter, Andreas; Laudadio, Emiliano; Mencarelli, Davide
Classificazione: 1 Contributo su Rivista
Abstract: Self-consistent charge density functional tight-binding (DFTB) calculations have been performed to investigate the electrical properties and transport behavior of asymmetric graphene devices (AGDs). Three different nanodevices constructed of different necks of 8 nm, 6 nm and 4 nm, named Graphene-N8, Graphene-N6 and Graphene-N4, respectively, have been proposed. All devices have been tested under two conditions of zero gate voltage and an applied gate voltage of +20 V using a dielectric medium of 3.9 epsilon interposed between the graphene and the metallic gate. As expected, the results of AGD diodes exhibited strong asymmetric I(V) characteristic curves in good agreement with the available experimental data. Our predictions implied that Graphene-N4 would achieve great asymmetry (A) of 1.40 at |VDS| = 0.2 V with maximum transmittance (T) of 6.72 in the energy range 1.30 eV. More importantly, while the A of Graphene-N4 was slightly changed by applying the gate voltage, Graphene-N6/Graphene-N8 showed a significant effect with their A increased from 1.20/1.03 under no gate voltage (NGV) to 1.30/1.16 under gate voltage (WGV) conditions. Our results open up unprecedented numerical prospects for designing tailored geometric diodes.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/327579

Adsorption of Polylactic-co-Glycolic Acid on Zinc Oxide Systems: A Computational Approach to Describe Surface Phenomena
NANOMATERIALS
Autore/i: Mohebbi, Elaheh; Pavoni, Eleonora; Minnelli, Cristina; Galeazzi, Roberta; Mobbili, Giovanna; Sabbatini, Simona; Stipa, Pierluigi; Masoud Seyyed Fakhrabadi, Mir; Laudadio, Emiliano
Classificazione: 1 Contributo su Rivista
Abstract: Zinc oxide and polylactic-co-glycolic acid (ZnO-PLGA) nanocomposites are known to exhibit different biomedical applications and antibacterial activity, which could be beneficial for adding to wound dressings after different surgeries. However, possible cytotoxic effects along with various unexpected activities could reduce the use of these prominent systems. This is correlated to the property of ZnO, which exhibits different polymeric forms, in particular, wurtzite, zinc-blende, and rocksalt. In this study, we propose a computational approach based on the density functional theory to investigate the properties of ZnO-PLGA systems in detail. First, three different stable polymorphs of ZnO were considered. Subsequently, the abilities of each system to absorb the PLGA copolymer were thoroughly investigated, taking into account the modulation of electrical, optical, and mechanical properties. Significant differences between ZnO and PLGA systems have been found; in this study, we remark on the potential use of these models and the necessity to describe crucial surface aspects that might be challenging to observe with experimental approaches but which can modulate the performance of nanocomposites.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/329232

Insights into the interfaces of VO2(M) and VO2(B) polymorphs with different substrates
MATERIALS ADVANCES
Autore/i: Mohebbi, Elaheh; Pavoni, Eleonora; Pierantoni, Luca; Stipa, Pierluigi; Laudadio, Emiliano; Mencarelli, Davide
Classificazione: 1 Contributo su Rivista
Abstract: The phenomena arising at the interface between oxide materials and substrates can fundamentally and practically change the physical and chemical properties of the materials themselves. In this study, we employed density functional theory (DFT) calculations to elucidate the stability and optical properties of VO2(M) and VO2(B) interactions with substrates of sapphire(c-cut), sapphire(r-cut), SrTiO3(001), SrTiO3(111), SrNbO3(001), SrNbO3(111), LaAlO3(c-cut), and LaAlO3(r-cut). The surface calculations showed that the fully relaxed SrTiO3(111) and SrNbO3(001) possess the highest energies of 31.8 eV nm−2 and 21.15 eV nm−2 relative to other slabs, before optimizing with VO2(M) and VO2(B) polymorphs, respectively. The calculated adsorption energy indicated that the interface of VO2(M) and VO2(B) structures showed more stability on SrTiO3(001) and SrTiO3(111), with adsorption energy values of 2.83 eV and 0.91 eV, respectively. Furthermore, the optical absorption properties of the highest and lowest stable interfaces have been evaluated. The outcomes predicted that VO2(M)@SrTiO3(001) and VO2(B)@SrTiO3(111) have their optical adsorption in the visible light range, while VO2(M)@sapphire(c-cut) and VO2(B)@sapphire(c-cut) showed the main adsorption peak in the infrared region.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/327903

Graphene Monolayer Nanomesh Structures and Their Applications in Electromagnetic Energy Harvesting for Solving the Matching Conundrum of Rectennas
NANOMATERIALS
Autore/i: Dragoman, Mircea; Dinescu, Adrian; Aldrigo, Martino; Dragoman, Daniela; Mohebbi, Elaheh; Pavoni, Eleonora; Laudadio, Emiliano
Classificazione: 1 Contributo su Rivista
Abstract: In this paper, we investigate various graphene monolayer nanomesh structures (diodes) formed only by nanoholes, with a diameter of just 20 nm and etched from the graphene layer in different shapes (such as rhombus, bow tie, rectangle, trapezoid, and triangle), and their electrical properties targeting electromagnetic energy harvesting applications. In this respect, the main parameters characterizing any nonlinear device for energy harvesting are extracted from tens of measurements performed on a single chip containing the fabricated diodes. The best nano-perforated graphene structure is the triangle nanomesh structure, which exhibits remarkable performance in terms of its characteristic parameters, e.g., a 420 Ω differential resistance for optimal impedance matching to an antenna, a high responsivity greater than 103 V/W, and a low noise equivalent power of 847 pW/√Hz at 0 V.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/337261

Unveiling pyroelectricity in ferroelectric planar capacitors with area-selective wet etched hafnium zirconium oxide: from ab initio and multiphysics simulations to experiments
JPHYS ENERGY
Autore/i: Aldrigo, Martino; Zampa, Gian Marco; Dragoman, Mircea; Dinu, Livia Alexandra; Nastase, Florin; Romanitan, Cosmin; Parvulescu, Catalin; Brincoveanu, Oana; Iordanescu, Sergiu; Vulpe, Silviu; Laudadio, Emiliano; Mohebbi, Elaheh; Pavoni, Eleonora
Classificazione: 1 Contributo su Rivista
Abstract: In this work, a systematic approach aimed at investigating and validating a novel way of realizing pyroelectric harvesting is presented. Generating a direct-current (dc) signal through a temperature gradient within a less than 7 nm-thick ferroelectric zirconium-doped hafnium oxide (HZO) nano-film, embedded in planar interdigitated capacitors on high-resistivity silicon, is a new, simple, effective, and reproducible solution. Temperature-related structural modifications in HZO are first simulated using advanced ab initio calculations. Then, rigorous multiphysics simulations of the final devices provide insight into the expected performance of the pyroelectric harvester, as a function of temperature, contact area, and crystal orientation, showing a maximum open-circuit voltage of up to 900 mV. The fabrication of the harvesters involves the area-selective wet etching of the HZO layer to retain it exclusively in between the fingers of each capacitor. This choice maximizes the pyroelectric effect (which strongly depends on the area) and represents a new paradigm in the development of HZO-based electronics, which are conventionally built on ferroelectric continuous films. Experimental validation at both low frequencies and microwaves confirms the pyroelectric effect, exhibiting a significant increase in the output current for higher temperature gradients, and a generated dc voltage of several hundred millivolts.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/337262

Layered Double Hydroxides as Systems for Capturing Small-Molecule Air Pollutants: A Density Functional Theory Study
MOLECULES
Autore/i: Mohebbi, Elaheh; Minnelli, Cristina; Pavoni, Eleonora; Sisti, Laura; Laudadio, Emiliano; Stipa, Pierluigi
Classificazione: 1 Contributo su Rivista
Abstract: Air pollutants are usually formed by easily spreading small molecules, representing a severe problem for human health, especially in urban centers. Despite the efforts to stem their diffusion, many diseases are still associated with exposure to these molecules. The present study focuses on modeling and designing two-dimensional systems called Layered Double Hydroxides (LDHs), which can potentially trap these molecules. For this purpose, a Density Functional Theory (DFT) approach has been used to study the role of the elemental composition of LDHs, the type of counterion, and the ability of these systems to intercalate NO2 and SO2 between the LDH layers. The results demonstrated how the counterion determines the different possible spacing between the layers, modulating the internalization capacity of pollutants and determining the stability degree of the system for a long-lasting effect. The variations in structural properties, the density of states (DOS), and the description of the charge transfer have been reported, thus allowing the investigation of aspects that are difficult to observe from an experimental point of view and, at the same time, providing essential details for the effective development of systems that can counteract the spread of air pollutants
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/337260

Investigation on the Synergy between Membrane Permeabilizing Amphiphilic α-Hydrazido Acids and Commonly Used Antibiotics against Drug-Resistant Bacteria
MOLECULES
Autore/i: Minnelli, Cristina; Mangiaterra, Gianmarco; Laudadio, Emiliano; Citterio, Barbara; Rinaldi, Samuele
Classificazione: 1 Contributo su Rivista
Abstract: The growth of (multi)drug resistance in bacteria is among the most urgent global health issues. Monocationic amphiphilic α-hydrazido acid derivatives are structurally simple mimics of antimicrobial peptides (AMPs) with fewer drawbacks. Their mechanism of membrane permeabilization at subtoxic concentrations was found to begin with an initial electrostatic attraction of isolated amphiphile molecules to the phospholipid heads, followed by a rapid insertion of the apolar portions. As the accumulation into the bilayer proceeded, the membrane increased its fluidity and permeability without being subjected to major structural damage. After having ascertained that α-hydrazido acid amphiphiles do not interact with bacterial DNA, they were subjected to synergy evaluation for combinations with conventional antibiotics. Synergy was observed for combinations with tetracycline against sensitive S. aureus and E. coli, as well as with ciprofloxacin and colistin against resistant strains. Additivity with a remarkable recovery in activity of conventional antibiotics (from 2-fold to ≥32-fold) together with largely subtoxic concentrations of α-hydrazido acid derivatives was found for combinations with ciprofloxacin toward susceptible S. aureus and methicillin toward MRSa. However, no potentiation of conventional antibiotics was observed for combinations with linezolid and gentamicin against the corresponding resistant S. aureus and E. coli strains.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/333952

Band gap and THz optical adsorption of SnSe and SnSe2 nanosheets on graphene: Negative dielectric constant of SnSe
RESULTS IN PHYSICS
Autore/i: Mohebbi, Elaheh; Pavoni, Eleonora; Pierantoni, Luca; Stipa, Pierluigi; Zampa, Gian Marco; Laudadio, Emiliano; Mencarelli, Davide
Classificazione: 1 Contributo su Rivista
Abstract: Density functional theory (DFT) calculations have been used to investigate physical–chemical sensing of various proposed interfaces as SnSe@Graphene, SnSe2@Graphene, Graphene@SnSe@Graphene, and Graphene@SnSe2@Graphene, where dispersion corrections have been included to taken into account the vdW interactions between the layers. Initially, we predicted the electronic structures, mobility and carrier concentrations (cc) of SnSe and SnSe2 structures. Using different methodology, the outcomes have confirmed the semiconductor properties of SnSe and SnSe2 with indirect bandgap of 1.20 eV and 0.94 eV calculated by Generalized Gradient Approximation (GGA) and MetaGGA (MGGA) adopted with Perdew-Burke-Ernzerhof (PBE) functional, while hybrid Heyd-Scuseria-Ernzerhof (HSE) hybrid functional overestimated the experimental observations for both materials. Room temperature high mobility and cc have predicted by 126 × 103 cm2V−1 s−1 with cc of 1.3 × 1013 cm3 for a two layers SnSe and 69 × 103 cm2V−1 s−1 with cc of 4.2 × 1018 cm3 for three layers SnSe2. Optical absorption spectrum revealed that the presence of two peaks at 60 THz and 48 THz with the intensity of 89879 cm−1 and 34504 cm−1 for interfaces including two layers of graphene. More interestingly, dielectric constant calculations showed that the transfer of carriers between graphene layers and SnSe in Graphene@SnSe@Graphene interface with absorption peak shifted to 24 THz along the in-plane direction and negative dielectric constants in the range of 24–169 THz, showing the effect of light-trapping through plasmonic.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/326952

Effect of different pseudopotentials on the phonon frequencies, dielectric constant, and Born effective charge of SnSe and SnSe2 nanostructures: A density functional perturbation theory study
JOURNAL OF PHYSICS AND CHEMISTRY OF SOLIDS
Autore/i: Mohebbi, Elaheh; Pavoni, Eleonora; Pierantoni, Luca; Stipa, Pierluigi; Laudadio, Emiliano; Mencarelli, Davide
Classificazione: 1 Contributo su Rivista
Abstract: The choice of the pseudopotentials (PPs) is a crucial step towards an accurate atomistic calculation of physical properties of 2D materials. In this study, based on Density-Functional Perturbation Theory (DFPT), we investigated the dependency of the phonon properties such as phonon frequencies, dielectric constant, Born effective charge, and vibrational modes of SnSe and SnSe2 monolayers to the different types of PPs. On the basis of Generalized Gradient Approximation (GGA) using PBE functional, we computed eight phonon calculations for both lattices in combinations with four different PPs including Normconversing (NC) FHI/HGH, Ultrasoft (USPP), and Standard Solid-State (SSSP), while other parameters like cut-off energy, k-points mesh, and convergence threshold were kept fixed. However, the phonon properties of acoustic and optical phonons were better predicted by USPP and SSSP for phonon dispersion of SnSe and SnSe2, respectively. Regarding the dielectric constant and Bohr effective charge calculations, our results showed that SnSe and SnSe2 structures possess the dielectric tensor of 8.9 and 6.6 along the in-plane direction by using USPP calculations. Our outcomes also revealed less sensitivity of SnSe2 polarization to the type of PPs by applying the electric field. This study recommends USPP and SSSP to further phonon analysis of other semiconductors.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/324392

First principles study of WSe2 and the effect of V doping on the optical and electronic properties
MATERIALS ADVANCES
Autore/i: Pavoni, E.; Mohebbi, E.; Zampa, G. M.; Stipa, P.; Pierantoni, L.; Laudadio, E.; Mencarelli, D.
Classificazione: 1 Contributo su Rivista
Abstract: Tungsten diselenide WSe2 is a material with an intriguing character that has captivated the attention of researchers; in this study, an ab initio analysis is presented that focuses on the optical and electronic properties of WSe2. The study made use of density functional theory (DFT) by employing the Perdew– Burke–Ernzerhof (PBE) generalized gradient approximation (GGA) density functional and PseudoDojo pseudopotential. The study looked at the properties of both bulk and monolayer WSe2 to determine how the number of layers affects the properties of the material. To further investigate the properties of WSe2, four different systems based on vanadium doped-WSe2 were analyzed from the optical and electronic points of view. The systems contained different percentages of V: (i) WSe2:V 1.4%, (ii) WSe2:V 2.8%, (iii) WSe2:V 5.6%, and (iv) WSe2:V 11.2%. The introduction of vanadium brought about a reduction of the bandgap and a global shift of the projected density of states. The valence band maximum (VBM) also crossed the Fermi level, which is consistent with the p-type nature of vanadium doping. Furthermore, the absorption spectra changed in terms of the position and the intensity of the optical transition as a result of vanadium introduction
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/325661

Strong enhancement of graphene plasmonic emission by quantum Čerenkov effect in confined structures
APPLIED PHYSICS LETTERS
Autore/i: Zampa, Gian Marco; Mencarelli, Davide; Mohebbi, Elaheh; Pavoni, Eleonora; Pierantoni, Luca; Laudadio, Emiliano
Classificazione: 1 Contributo su Rivista
Abstract: One notable issue in low terahertz (THz) applications is to achieve sources with higher output power than the state of the art. One possible solution to the foregoing problem is to amplify the electromagnetic field emitted by already accessible THz generators. Here, we study the quantum Cerenkov effect as a possible explanation for low-THz amplification, which has been found experimentally elsewhere. Specifically, the emission of surface plasmons from traveling electrons in mono-dimensional graphene, mediated by charge–field interaction, is shown to provide in-plane electromagnetic radiation down to THz and mm-wave frequencies. We focus on a structure consisting of a graphene layer between metal electrodes, which enhance the field confinement and lead to a linearization of the plasmon dispersion in the frequency domain. When compared to a non-confined plasmonic radiation, the above-mentioned configuration shows emission rates ten times larger, which make it promising for THz amplification.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/340993

Quantum tunnelling in hafnia-based metal-insulator-metal diodes: atomistic-to-continuum modelling approach and experimental validation
PHYSICA SCRIPTA
Autore/i: Pavoni, Eleonora; Laudadio, Emiliano; Christopher, Hardly Joseph; Zampa, Gian Marco; Russo, Paola; Mohebbi, Elaheh; Mencarelli, Davide; Dragoman, Mircea; Stipa, Pierluigi; Pierantoni, Luca; Aldrigo, Martino
Classificazione: 1 Contributo su Rivista
Abstract: In this work, we present a metal-insulator-metal (MIM) diode, based on quantum tunnelling phenomena. Its model is based on a multilevel modelling approach consisting of atomistic and continuum simulations, fully validated by extensive measurements. The MIM structure comprises a hafnium oxide (or hafnia, HfO2) dielectric layer, less than 4 nm thick and a square contact area of only 4 μm2, placed between two metallic electrodes, namely platinum as the source and titanium as the drain. The current–voltage (I–V) curve has been estimated by Density Functional Theory (DFT) calculations through an optimisation of the interfaces between metals and monoclinic HfO2. The dielectric parameters arising from ab initio computations have then been used as inputs for the successive circuit and electromagnetic simulations. Finally, the multilevel model has been validated with great accuracy, first measuring the I–V characteristics by applying a drain-source voltage between −1 V and +1 V, and then extracting the scattering parameters up to 40 GHz, thus demonstrating that DFT and circuit/electromagnetic simulations match almost perfectly the experimental ones. These outcomes represent the first study of such nanoscale devices investigated by means of a rigorous atomistic-to-continuum approach, providing invaluable information in order to improve fabrication and correctly assess the macroscale performance of nanoelectronics systems.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/326511

Chemical Scaffolds for the Clinical Development of Mutant-Selective and Reversible Fourth-Generation EGFR-TKIs in NSCLC
ACS CHEMICAL BIOLOGY
Autore/i: Laudadio, Emiliano; Mangano, Luca; Minnelli, Cristina
Classificazione: 1 Contributo su Rivista
Abstract: In nonsmall cell lung cancer (NSCLC), as well as in other tumors, the targeted therapy is mainly represented by tyrosine kinase inhibitors (TKIs), small molecules able to target oncogenic driver alterations affecting the gene encoding the epidermal growth factor receptor (EGFR). Up to now, several different TKIs have been developed. However, cancer cells showed an incredible adaptive tumor response to the inhibition of the sequentially mutated EGFR (EGFRM+), triggering the need to explore novel pharmacochemical strategies. This Review summarizes the recent efforts in the development of new reversible next-generation EGFR TKIs to fight the resistance against T790M and C797S mutations. Specifically, after giving an overview of the role of the EGFR's signaling pathways in cancer progression, we are going to discuss the most relevant approved drugs and drug candidates in terms of chemical structure, binding modalities, and their potency and selectivity against the mutated EGFR over the wild-type form. This could provide important guidelines and rationale for the discovery and iterative development of new drugs.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/328431

Copper-Layered Double Hydroxide for Methanol Electrooxidation: A Combined DFT and Experimental Characterization
2024 IEEE International Workshop on Metrology for Living Environment, MetroLivEnv 2024 - Proceedings
Autore/i: Minnelli, C.; Gramigni, D.; Pavoni, E.; Ripani, L.; Laudadio, E.; Mobbili, G.; Barucca, G.; Stipa, P.; Galeazzi, R.; Mengucci, P.; Mohebbi, E.; Romagnoli, E.; Marcaccio, M.
Editore: Institute of Electrical and Electronics Engineers Inc.
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Abstract: Exposure to volatile organic compounds (VOCs) can cause several health problems both in humans and animals. Among them, methanol (CH3OH), the most abundant oxygenated VOCs present in the troposphere, is a precursor of carbon monoxide (CO) and formaldehyde (CH3CHO) but it is also one of the simplest molecules used as a fuel for cleaner energy production. The aim of this research aspires to design and characterize promising advanced functional sensor-material based on CH3OH oxidation to either drive energy conversion, detect the methanol concentration and/or prevent environmental methanol pollution. The electrochemical methanol oxidation reaction (MOR) is a meaningful pathway to obtain these aims since the low potential is required for reaction occurrence. In the context of the development of sustainable and economic sensor-material, layered double hydroxide (LDH) based on Cu is a very promising one. Two different LDH copper-based composites were synthetized and characterized by means of X-ray diffraction experiments, electrochemical measurements, and atomistic simulations. Results showed a crucial structural role played by the type of M(II) ion present in the structure of the LDH. In particular, copper-based LDH containing Zn(II) exhibits a stronger ability to oxidize CH3OH than those containing Mg(II). The atomistic simulations indicate a sort of cooperative affect by the Zn(II), most probably through an enhanced adsorption phenomenon which is relevant in the mediated electron transfer by the active species Cu(III). Overall, this work highlighted the prevision potential of the in silico studies which will be useful to faster screen of different materials followed by selection and synthesis of those showing the optimal features in terms of pollutant adsorption and structure stability. This combined experimental-in silico approach could therefore lead to a faster design and optimization of effective functional materials for applications in indoor and outdoor quality.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/336545

First-Principles Calculation of MoO2 and MoO3 Electronic and Optical Properties Compared with Experimental Data
NANOMATERIALS
Autore/i: Pavoni, Eleonora; Modreanu, MIRCEA GABRIEL; Mohebbi, Elaheh; Mencarelli, Davide; Stipa, Pierluigi; Laudadio, Emiliano; Pierantoni, Luca
Classificazione: 1 Contributo su Rivista
Abstract: MoO3 and MoO2 systems have attracted particular attention for many widespread applications thanks to their electronic and optical peculiarities; from the crystallographic point of view, MoO3 adopts a thermodynamically stable orthorhombic phase (α-MoO3) belonging to the space group Pbmn, while MoO2 assumes a monoclinic arrangement characterized by space group P21/c. In the present paper, we investigated the electronic and optical properties of both MoO3 and MoO2 by using Density Functional Theory calculations, in particular, the Meta Generalized Gradient Approximation (MGGA) SCAN functional together with the PseudoDojo pseudopotential, which were used for the first time to obtain a deeper insight into the nature of different Mo–O bonds in these materials. The calculated density of states, the band gap, and the band structure were confirmed and validated by comparison with already available experimental results, while the optical properties were validated by recording optical spectra. Furthermore, the calculated band-gap energy value for the orthorhombic MoO3 showed the best match to the experimental value reported in the literature. All these findings suggest that the newly proposed theoretical techniques reproduce the experimental evidence of both MoO2 and MoO3 systems with high accuracy.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/314849

Cytotoxicity in vitro of two non-commercial samples of chrysotile and fibrous erionite
PERIODICO DI MINERALOGIA
Autore/i: Pugnaloni, Armanda; DI VALERIO, Silvia; Tossetta, Giovanni; Armeni, Tatiana; Cianfruglia, Laura; Tiano, Luca; Marchegiani, Fabio; Stipa, Pierluigi; Laudadio, Emiliano; Sabbatini, Simona; Minnelli, Cristina; Vaiasicca, Salvatore; Ramini, Debora; Procopio, Antonio D.; Fazioli, Francesca; Francesco Gualtieri, Alessandro
Classificazione: 1 Contributo su Rivista
Abstract: Exposure to naturally occurring asbestos and fibrous erionite can have severe impacts for the human health and cause malignant mesothelioma. The disease burden associated with this exposure is difficult to quantify and is not properly investigated. A characterization of the crystal-chemical-physical properties and toxicity/carcinogenicity of naturally occurring fibres with attention to asbestos and erionite is therefore highly recommended. The present study deals with the in vitro biological effects in MeT5A and A549 human cell lines of two non-commercial asbestos fibres: Valmalenco chrysotile from Central Alps Italy and fibrous erionite from Jersey Nevada, USA, including the standards UICC Chrysotile and UICC crocidolite. Light and scanning electron microscopy (SEM) observations showed morphological cell perturbation of treated cells. SEM-EDAX investigations revealed that the release of chemical components in the culture media affect cell viability. ROS levels increased in accordance with glutathione depletion, witnessing a remarkable cellular stress. Free radical release on pristine fibres was investigated by means of electron paramagnetic resonance (EPR) spin trapping technique and FTIR spectroscopy to characterize the molecular structures of fibres. Results reflect the cytotoxic effects and evidence the different toxicity pathways prompted by these fibre species due to their different crystal assemblages and physical properties.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/323351

Identification of Flavone Derivative Displaying a 4'-Aminophenoxy Moiety as Potential Selective Anticancer Agent in NSCLC Tumor Cells
MOLECULES
Autore/i: Mobbili, Giovanna; Romaldi, Brenda; Sabbatini, Giulia; Amici, Adolfo; Marcaccio, Massimo; Galeazzi, Roberta; Laudadio, Emiliano; Armeni, Tatiana; Minnelli, Cristina
Classificazione: 1 Contributo su Rivista
Abstract: Five heterocyclic derivatives were synthesized by functionalization of a flavone nucleus with an aminophenoxy moiety. Their cytotoxicity was investigated in vitro in two models of human non-small cell lung cancer (NSCLC) cells (A549 and NCI-H1975) by using MTT assay and the results compared to those obtained in healthy fibroblasts as a non-malignant cell model. One of the aminophenoxy flavone derivatives (APF-1) was found to be effective at low micromolar concentrations in both lung cancer cell lines with a higher selective index (SI). Flow cytometric analyses showed that APF-1 induced apoptosis and cell cycle arrest in the G2/M phase through the up-regulation of p21 expression. Therefore, the aminophenoxy flavone-based compounds may be promising cancer-selective agents and could serve as a base for further research into the design of flavone-based anticancer drugs.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/314597

Structural Basis for Agonistic Activity and Selectivity toward Melatonin Receptors hMT1 and hMT2
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Autore/i: Cantarini, M.; Rusciano, D.; Amato, R.; Canovai, A.; Cammalleri, M.; Monte, M. D.; Minnelli, C.; Laudadio, E.; Mobbili, G.; Giorgini, G.; Galeazzi, R.
Classificazione: 1 Contributo su Rivista
Abstract: Glaucoma, a major ocular neuropathy originating from a progressive degeneration of retinal ganglion cells, is often associated with increased intraocular pressure (IOP). Daily IOP fluctuations are physiologically influenced by the antioxidant and signaling activities of melatonin. This endogenous modulator has limited employment in treating altered IOP disorders due to its low stability and bioavailability. The search for low-toxic compounds as potential melatonin agonists with higher stability and bioavailability than melatonin itself could start only from knowing the molecular basis of melatonergic activity. Thus, using a computational approach, we studied the melatonin binding toward its natural macromolecular targets, namely melatonin receptors 1 (MT1) and 2 (MT2), both involved in IOP signaling regulation. Besides, agomelatine, a melatonin-derivative agonist and, at the same time, an atypical antidepressant, was also included in the study due to its powerful IOP-lowering effects. For both ligands, we evaluated both stability and ligand positioning inside the orthosteric site of MTs, mapping the main molecular interactions responsible for receptor activation. Affinity values in terms of free binding energy (ΔGbind) were calculated for the selected poses of the chosen compounds after stabilization through a dynamic molecular docking protocol. The results were compared with experimental in vivo effects, showing a higher potency and more durable effect for agomelatine with respect to melatonin, which could be ascribed both to its higher affinity for hMT2 and to its additional activity as an antagonist for the serotonin receptor 5-HT2c, in agreement with the in silico results.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/311973

Density functional theory and molecular dynamics studies on electrical, mechanical, and thermal properties of TiO2 nanoparticles interacting with poly lactic-co-glycolic acid
COLLOIDS AND SURFACES. A, PHYSICOCHEMICAL AND ENGINEERING ASPECTS
Autore/i: Laudadio, Emiliano; Mohebbi, Elaheh; Pavoni, Eleonora; Minnelli, Cristina; Sabbatini, Simona; Stipa, Pierluigi
Classificazione: 1 Contributo su Rivista
Abstract: Poly-lactic poly-co-glycolic acid (PLGA) copolymer is widely used thanks to its biocompatibility, even if could be difficult to find desirable mechanical properties for the polymer matrix. For this reason, inorganic nanoparticles like titanium dioxide (TiO2) can be used to modulate the mechanical properties of systems maintaining their biological capabilities. In this concern, density functional theory (DFT) and molecular dynamics (MD) simulations have been used to study the absorption phenomena of PLGA on surfaces of I4₁/amd (Anatase), P42/mnm (Rutile), and Pbca (Brookite) polymorphs of TiO2 DFT results showed that Anatase TiO2 is the best choice to absorb PLGA in comparison to the other PLGA-TiO2 surfaces. MD simulations remarked a peculiar stabilization pathway of PLGA-TiO2 with Anatase surface along the MD time and the largest increase in both Young’s and Bulk’s moduli. Finally, the influence of temperature on the mechanical properties of PLGA/A-TiO2 has also been investigated; in particular, MD results revealed that Young’s modulus of nanocomposite and the binding energy decreased by increasing the temperature. The outcomes of the present investigation could be helpful to clarify the potential uses of the PLGA-TiO2 nanocomposites in the biomedical field ranging from bone tissue engineering to drug delivery.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/313852

Harvesting microwave energy using pyroelectricity of nanostructured graphene/zirconium-doped hafnium oxide ferroelectric heterostructures
NANOTECHNOLOGY
Autore/i: Dragoman, Mircea; Aldrigo, Martino; Dinescu, Adrian; Vasilache, Dan; Iordanescu, Sergiu; Dragoman, Daniela; Laudadio, Emiliano; Pavoni, Eleonora
Classificazione: 1 Contributo su Rivista
Abstract: In this work, we present the design, atomistic/circuit/electromagnetic simulations, and the experimental results for graphene monolayer/zirconium-doped hafnium oxide (HfZrO) ultra-thin ferroelectric-based field effect transistors fabricated at the wafer scale, regarding the pyroelectricity generation directly from microwave signals, at room temperature and below it, namely at 218 K and at 100 K. The transistors work like energy harvesters, i.e. they collect low-power microwave energy and transform it into DC voltages with a maximum amplitude between 20 and 30 mV. The same devices function as microwave detectors in the band 1-10.4 GHz and at very low input power levels not exceeding 80μW when they are biased by using a drain voltage, with average responsivity values in the range 200-400 mV mW-1.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/312968

Integration of Lipid-Functionalized Epigallocatechin-3-gallate into PLGA Matrix as a Novel Polyphenol-Based Nanoantioxidant
ACS OMEGA
Autore/i: Minnelli, Cristina; Stipa, Pierluigi; Mobbili, Giovanna; Sabbatini, Simona; Romaldi, Brenda; Armeni, Tatiana; Laudadio, Emiliano
Classificazione: 1 Contributo su Rivista
Abstract: The search for polyphenol-based materials with antioxidant activity is a growing research area in the biomedical field. To obtain an efficient and stable nanoantioxidant, a novel biosystem was designed by integrating a lipophilic derivative of epigallocatechin-3-gallate (named EGCG-C18) on the surface of poly(lactic-co-glycolic acid) (PLGA). Poly(vinyl alcohol) (PVA) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol) (DSPE-PEG2000) were selected as polymeric and lipidic stabilizers, respectively, and their influence on both physical properties and the antioxidant activity of nanoantioxidant was investigated by a combined in silico and experimental approach. Full-atom molecular dynamics (MD) simulations were carried out to describe the different self-assembly processes of all components and the interactions that guided the EGCG-C18 insertion inside the PLGA matrix. Together with infrared spectroscopy results, the formation of an antioxidant lipid shell on the PLGA surface was clear. Dynamic light scattering and transmission electron microscopy showed that in the presence of DSPE-PEG2000, NPs were smaller than those treated with PVA. In addition, the different stabilizers used strongly influenced the ROS-scavenging ability of nanomaterials and this effect was strictly related to the molecular organization of EGCG-C18. MD showed that the apolar interaction between the alkyl chains of DSPE-PEG2000 and EGCG-C18 oriented the phenolic groups of the polyphenol toward the solvent, providing an ability of NP to scavenge hydroxyl radicals over to free EGCG-C18 and PLGA/PVA NPs. Finally, the ability of nanoantioxidants to protect human dermal fibroblasts from cell death induced by oxidative stress has been tested, revealing the high potential of these novel NPs as polyphenol-based materials.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/325971

Insights Into a New Geometric Graphene Diode with Ultrahigh Asymmetry Ratio: A Computational Approach
Proceedings of the IEEE Conference on Nanotechnology
Autore/i: Mohebbi, E.; Pavoni, E.; Pierantoni, L.; Stipa, P.; Laudadio, E.; Mencarelli, D.
Editore: IEEE Computer Society
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Abstract: In this study, we introduce a novel concept of the transport properties of three proposed geometric graphene diodes based on self-consistent charge density functional tight-binding method. The calculations have been performed with bias voltages up to a few volts suitable for electronics applications. Geometrical graphene devices based ballistic region exhibited strong nonlinear I(V) characteristic curves as well as desirable current amounts. The results indicated that the graphene Device C with an edge width 5nm and angle of 47° showed an excellent current value of 213 μA at 1.5V, which was higher than other two devices A and B with edge widths 9 nm and 5nm and corresponding angle 61°. A maximum AR of 2.23 has been achieved at a current of 137 μA for Device C, which is among the highest values for a geometric graphene device reported to date. This study provides a pathway for optimizing the graphene diodes to be used as potential applications for energy harvesting devices.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/326753

In vitro toxicity of short vs long chrysotile fibres
PERIODICO DI MINERALOGIA
Autore/i: Gualtieri, Alessandro; Mirata, Serena; Almonti, Vanessa; Maria Bassi, Anna; Meo, Chiara; Scarfì, Sonia; Zapparoli, Mauro; Armeni, Tatiana; Cianfruglia, Laura; Marzioni, Daniela; Fantone, Sonia; Tossetta, Giovanni; Stipa, Pierluigi; Laudadio, Emiliano; Sabbatini, Simona; Minnelli, Cristina; DI VALERIO, Silvia; Vaiasicca, Salvatore; Procopio, Antonio; Pugnaloni, Armanda
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/323471

In vitro toxicity of short vs long chrysotile fibres
Autore/i: Gualtieri, Alessandro; Mirata, Serena; Almonti, Vanessa; Bassi Anna, Maria; Meo, Chiara; Scarfì, Sonia; Zapparoli, Mauro; Armeni, Tatiana; Cianfruglia, Laura; Marzioni, Daniela; Fantone, Sonia; Tossetta, Giovanni; Stipa, Pierluigi; Laudadio, Emiliano; Sabbatini, Simona; Minnelli, Cristina; DI VALERIO, Silvia; Vaiasicca, Salvatore; Procopio, Antonio; Pugnaloni, Armanda
Classificazione: 1 Contributo su Rivista
Abstract: Chrysotile is a natural hydrous layer silicate that belongs to the serpentine group. Because of its unique asbestiform shape and outstanding physical-chemical properties, chrysotile is still nowadays the most used commercial mineral fibre in the world. This occurs despite the mineral has been classified as a Group 1 carcinogen by the International Agency for Research on Cancer (IARC). Since the “fibre toxicity paradigm” relies on the fibre size (length L and width W) and biodurability, the present work attempts to shed light on the issue of the toxicity of short vs. long chrysotile fibres by investigating two size-separated batches of chrysotile fibres (L>5 mm and L≤5 mm) of a commercial Russian sample. In parallel, UICC crocidolite and NYAD G wollastonite fibres were used as a positive and a negative carcinogenic standard, respectively. The calculated fibre potential toxicity/pathogenicity index (FPTI) value of the long-fibre chrysotile (2.35) is greater than that of the short-fibre (2.18) predicting a greater potential of toxicity/pathogenicity of the former. The FTPI value of short-fibre chrysotile is greater than that of wollastonite (1.92-2.12) but lower than that of crocidolite (2.67). The theoretical predictions were complemented with in vitro toxicity tests performed in parallel on four different cell types involved in the toxicity of inhaled mineral fibres: alveolar, endothelial, mesothelial cells and macrophages. The results from the MTT and LDH toxicity and ROS production tests are in line with the FPTI prediction. The negative carcinogenic standard wollastonite displays the lower in vitro toxicity score (0.25), while the short-fibre chrysotile presents a higher score (0.43), followed by the long-fibre chrysotile (0.66) and the positive carcinogenic standard crocidolite (0.67).In conclusion, our in vitro acute toxicity results on chrysotile are in line with the FPTI model predictions, indicating that short chrysotile asbestos fibres should not be assimilated to “innocuous dusts”

First-principles investigation of interface phenomena in hafnium-based metal–insulator–metal diodes
NANOSCALE ADVANCES
Autore/i: Pavoni, Eleonora; Mohebbi, Elaheh; Stipa, Pierluigi; Pierantoni, Luca; Mencarelli, Davide; Dragoman, Mircea; Aldrigo, Martino; Laudadio, Emiliano
Classificazione: 1 Contributo su Rivista
Abstract: Metal–insulator–metal (MIM) diodes are very interesting in many different applications exploiting environment-friendly renewable energy solutions. Moreover, since the dimensions of such devices are at the nanoscale, the size and the characteristics of their constitutive elements can drastically influence their macroscale performance. As it could be difficult to describe in detail the physical phenomena occurring among materials in nanoscale systems, in this work first-principles calculations have been used to study the structural and electrical properties of three different hafnium oxide (HfO2)-MIM diodes. These devices have been simulated at the atomistic level by interposing 3 nm of HfO2 between drain and source electrodes made of gold and platinum, respectively. The monoclinic and orthorhombic polymorphs of HfO2 have been considered to model different types of MIM diodes, and the interface geometries have been optimized to compute the current–voltage characteristics, reflecting the tunneling mechanisms occurring in such devices. The calculation of the transmission pathways has also been carried out to investigate the effects of atomistic coordinates despite the use of the same material. The results demonstrate the role of the Miller indices of metals and the influence of the HfO2 polymorphs on the MIM properties. In this study, the importance of interface phenomena on the measurable properties of the proposed devices has been investigated in detail.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/313853

Mechanistic insight toward EGFR activation induced by ATP: role of mutations and water in ATP binding patterns
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
Autore/i: Laudadio, Emiliano; Mobbili, Giovanna; Sorci, Leonardo; Galeazzi, Roberta; Minnelli, Cristina
Classificazione: 1 Contributo su Rivista
Abstract: The discovery of mutations within the kinase domain of the epidermal growth factor receptor (EGFR) gene has enabled a new era of targeted therapy in non-small cell lung cancer (NSCLC). Drugs belonging to the family of tyrosine kinase inhibitors (TKIs) are designed to bind ATP binding cleft, anyway, the occurrence of aminoacidic mutations decreases the effectiveness of the antitumoral treatment. Despite many efforts has been already made, the impact of the mutations on conformation and stability of EGFR-ATP complexes is still not fully understood. Therefore, we investigated the effect of mutations that leads to changes in Michaelis-Menten constant (Km) using dynamic docking simulations. We focused on six different EGFR forms in relation to different mutation states, then we found a good correlation between the calculated ATP affinities and Km values. Moreover, since dynamic switching of TKEGFR from the inactive towards the active state is known to regulate the kinase activity, we observed that ATP induces the inwards movement of the aC-helix with the Lys745 close to Glu762 in all cases. This means that ATP binding should be the first step in promoting the conformational shift to the active state. Finally, we highlighted for the first time the key contribution of water hydrogen bond and water-bridge networks in the modulation of ATP affinity. The identified mutant-specific ATP binding patterns and conformational features could be much useful to guide cancer therapy and develop more personalized medicine.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/306582

Insights into PLGA-encapsulated epigallocatechin 3-gallate nanoparticles as a new potential biomedical system: A computational and experimental approach
EUROPEAN POLYMER JOURNAL
Autore/i: Minnelli, Cristina; Stipa, Pierluigi; Sabbatini, Simona; Mengucci, Paolo; Mobbili, Giovanna; Galeazzi, Roberta; Armeni, Tatiana; Romaldi, Brenda; Celli, Annamaria; Laudadio, Emiliano
Classificazione: 1 Contributo su Rivista
Abstract: Biodegradable poly-lactic poly-glycolic copolymer (PLGA) represents one of the best strategies adopted to convey small molecules unstable and characterised by a low bioavailability if administered without vehicles. This is the case of Epigallocatechin-3-gallate (EGCG), which is one of the most interesting polyphenols from a biomedical point of view. In this study, the impact of EGCG on PLGA nanoparticles (NPs) properties has been studied underlining the role of the binary PVA/Poloxamer-407 as stabilizer system for obtaining colloidal stable NPs. Characterization has been carried out by dynamic light scattering (DLS), encapsulation efficiency, drug release studies, scanning electron microscopy (SEM) and infrared spectroscopy (IR). Molecular dynamics (MD) simulations have been used to model the PLGA and EGCG systems to understand the behaviour of NPs and the interactions that guided the EGCG encapsulation. The nanodispersions exhibited promising cytotoxic potentials in human lung carcinoma A549 cell lines enhancing the well-known growth inhibitor effect of the free EGCG.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/309751

Stability, phonon calculations, electronic structure, and optical properties of a VO2(M) nanostructure: A comprehensive density functional theory study
FRONTIERS IN MATERIALS
Autore/i: Mohebbi, Elaheh; Pavoni, Eleonora; Mencarelli, Davide; Stipa, Pierluigi; Laudadio, Emiliano; Pierantoni, Luca
Classificazione: 1 Contributo su Rivista
Abstract: This work aimed to precisely evaluate the physical properties of vanadium dioxide (M), particularly the optical characteristics. We employed different exchangecorrelation functionals to determine the phase stability, band gap properties, and optical characteristics of an experimentally recognized monoclinic VO2(M) polymorph. The calculations not only correctly interpreted the VO2(M) origin but also predicted other optical properties including the extinction coefficient (k) and refractive index (n), which have not been reported in experimental measurements. Phonon dispersion calculations confirmed the presence of negative frequencies for acoustic modes in the phononic curves. When the HSE functional correctly reproduced the experimental band gap, here for the first time, our calculations based on PBE and PBEsol yielded non-zero electronic bandgaps of 0.23 and 0.15 eV for bulk VO2(M). Our predictions showed that semilocal functionals can adequately predict the semiconductor properties of VO2(M) and performed better than all previously reported theoretical works on nulled band gaps. In addition to the better prediction of the peak position in the absorption spectra with HSE hybrid functional, this method also reasonably well described the static dielectric constant of 7.54, showing an excellent match to the experimental values. In general, the results of this study reveal that hybrid functionals yield superior outcomes compared to semi-local functionals for optical properties of a VO2(M) polymorph. Our results suggest that the PBEsol + HSE approach allows the efficient characterization of smart materials for electronic and optoelectronic applications.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/312967

Effect of Wet and Dry Environments in CNC/MWCNTs/Ag2O Electrically Conductive Films: Material Characterization and Molecular Dynamics Simulation
JOURNAL OF PHYSICAL CHEMISTRY. C
Autore/i: Luzi, Francesca; Angulo Dehesa, Ainhoa; Laudadio, Emiliano; Puglia, Debora; Lizundia, Erlantz; Stipa, Pierluigi; Armentano, Ilaria; Torre, Luigi
Classificazione: 1 Contributo su Rivista
Abstract: Electrically-conducting biobased materials present a bright future to be used in high-technological applications including sensors, soft electronics and active packaging. Accordingly, in this work we develop and characterize ternary nanohybrid films combining cellulose nanocrystals (CNC), multi-walled carbon nanotubes (MWCNTs) and silver oxide (Ag2O) nanoparticles. An evaporation-induced self-assembly process is applied to obtain homogenously dispersed free-standing nanocomposite films as proven by electron microscopy observations. Thermogravimetric analyses show that while MWCNTs delay the cleavage of glycosidic linkages of cellulose, Ag2O catalyzed thermodegradation events to render materials with reduced thermal stabilities. The electrical and dielectrical properties of the nanohybrid materials are analysed under completely dry and 53% humidity atmospheres and the results are observed also in the light of the electric modulus. Water increases the conductivity of binary and ternary systems and shift the electric modulus relaxation peak. Finally, full atom molecular dynamics simulations are performed for the first time to better describe the phenomena on interfaces between nanoscale systems, underlying mechanisms for the obtained electrical AC and DC results. Computational results reveal changes in the CNC/MWCNT/Ag2O interactions depending on the water presence, more different types of interactions are found in relation to the type of nanomaterial. The combination of experimental and simulation data here shown sheds further light on the electric conducting mechanism of nanocellulose-based materials with multifunctional properties.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/324776

The Effect of Y Doping on Monoclinic, Orthorhombic, and Cubic Polymorphs of HfO2: A First Principles Study
NANOMATERIALS
Autore/i: Pavoni, Eleonora; Mohebbi, Elaheh; Mencarelli, Davide; Stipa, Pierluigi; Laudadio, Emiliano; Pierantoni, Luca
Classificazione: 1 Contributo su Rivista
Abstract: HfO2 can assume different crystalline structures, such as monoclinic, orthorhombic, and cubic polymorphs, each one characterized by unical properties. The peculiarities of this material are also strongly related to the presence of doping elements in the unit cell. Thus, the present paper has the main purpose of studying and comparing twelve different systems characterized by diverse polymorphs and doping percentages. In particular, three different crystalline structures were considered: the monoclinic P21/c, the orthorhombic Pca21, and the cubic Fm3¯m phases of HfO2. Each one has been studied by using Y as a doping agent with three different contents: 0% Y:HfO2, 8% Y:HfO2, 12% Y:HfO2, and 16% Y:HfO2. For all the systems, density functional theory (DFT) methods based on PBE/GGA, and on the HSE hybrid functionals were used to optimize the geometry as well as to study their optical properties. Depending on the polymorphs, Y affects the formation energy in different ways and causes changes in the optical properties. When the percentage of Y did not exceed 12%, a stabilization of the cubic phase fraction and an increase of the dielectric constant was observed. Additionally, the calculated optical bandgap energies and the refractive index are examined to provide an overview of the systems and are compared with experimental data. The bandgaps obtained are in perfect agreement with the experimental values and show a slight increase as the doping percentage grows, while only minor differences are found between the three polymorphs in terms of both refractive index and optical band gap. The adopted first principles study generates a reasonable prediction of the physical-chemical properties of all the systems, thus identifying the effects of doping phenomena.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/309301

Insights into first-principles characterization of the monoclinic VO2(B) polymorph via DFT + U calculation: electronic, magnetic and optical properties
NANOSCALE ADVANCES
Autore/i: Mohebbi, Elaheh; Pavoni, Eleonora; Mencarelli, Davide; Stipa, Pierluigi; Pierantoni, Luca; Laudadio, Emiliano
Classificazione: 1 Contributo su Rivista
Abstract: We have studied the structural, electronic, magnetic, and optical properties of the VO2(B) polymorph using first-principles calculations based on density functional theory (DFT). This polymorph was found to display four optimized structures namely VO2(B)PP, VO2(B)LP, VO2(B)PPD, and VO2(B)LPD using the generalized gradient approximation (GGA) PBE exchange-correlation functional by including/excluding van der Waals interaction. Our derivation provides a theoretical justification for adding an on-site Coulomb U value in the conventional DFT calculations to allow a direct comparison of the two methods. We predicted a zero bandgap of the VO2(B) structure based on GGA/PBE. However, by GGA/PBE + U, we found accurate bandgap values of 0.76, 0.66, and 0.70 eV for VO2(B)PP, VO2(B)LP, and VO2(B)PPD, respectively. The results obtained from DFT + U were accompanied by a structural transition from the metallic to semiconductor property. Here, we verified the non-magnetic characteristic of the monoclinic VO2(B) phase with some available experimental and theoretical data. However, the debate on the magnetic property of this polymorph remains unresolved. Imaginary and real parts of the dielectric function, as computed with the GGA/PBE functional and the GGA/PBE + U functional, were also reported. The first absorption peaks of all considered geometries in the imaginary part of the dielectric constants indicated that the VO2(B) structure could perfectly absorb infrared light. The computed static dielectric constants with positive values, as derived from the optical properties, confirmed the conductivity of this material. Among the four proposed geometries of VO2(B) in this study, the outcomes obtained by VO2(B)PPD reveal good results owing to the excellent consistency of its bandgap, magnetic and optical properties with other experimental and theoretical observations. The theoretical framework in our study will provide useful insight for future practical applications of the VO2(B) polymorph in electronics and optoelectronics.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/306543

The Role of Zr on Monoclinic and Orthorhombic HfxZryO2 Systems: A First-Principles Study
MATERIALS
Autore/i: Pavoni, Eleonora; Mohebbi, Elaheh; Stipa, Pierluigi; Mencarelli, Davide; Pierantoni, Luca; Laudadio, Emiliano
Classificazione: 1 Contributo su Rivista
Abstract: HfO2 shows different polymorphs, including monoclinic and orthorhombic ones, that exhibit singular properties. Moreover, the character of HfO2 is also influenced by the Zr atoms as a doping agent. Here, an extensive study of the monoclinic P21/c and the orthorhombic Pca21 polymorphs of HfO2, Hf0.75Zr0.25O2, and Hf0.5Zr0.5O2 is reported. For all six systems, density functional theory (DFT) methods based on generalized gradient approximations (GGAs) were first used; then the GGA + U method was settled and calibrated to describe the electrical and optical properties of polymorphs and the responses to the oxygen vacancies. Zr had different effects in relation to the polymorph; moreover, the amount of Zr led to important differences in the optical properties of the Pca21 polymorph. Finally, oxygen vacancies were investigated, showing an important modulation of the properties of HfxZryO2 nanostructures. The combined GGA and GGA + U methods adopted in this work generate a reasonable prediction of the physicochemical properties of o- and m-HfxZryO2, identifying the effects of doping phenomena.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/303736

HIF-1-Dependent Induction of β3 Adrenoceptor: Evidence from the Mouse Retina
CELLS
Autore/i: Amato, R.; Pisani, F.; Laudadio, E.; Cammalleri, M.; Lucchesi, M.; Marracci, S.; Filippi, L.; Galeazzi, R.; Svelto, M.; Dal Monte, M.; Bagnoli, P.
Classificazione: 1 Contributo su Rivista
Abstract: A major player in the homeostatic response to hypoxia is the hypoxia-inducible factor (HIF)-1 that transactivates a number of genes involved in neovessel proliferation in response to low oxygen tension. In the retina, hypoxia overstimulates β-adrenoceptors (β-ARs) which play a key role in the formation of pathogenic blood vessels. Among β-ARs, β3-AR expression is increased in proliferating vessels in concomitance with increased levels of HIF-1α and vascular endothelial growth factor (VEGF). Whether, similarly to VEGF, hypoxia-induced β3-AR upregulation is driven by HIF-1 is still unknown. We used the mouse model of oxygen-induced retinopathy (OIR), an acknowledged model of retinal angiogenesis, to verify the hypothesis of β3-AR transcriptional regulation by HIF-1. Investigation of β3-AR regulation over OIR progression revealed that the expression profile of β3-AR depends on oxygen tension, similar to VEGF. The additional evidence that HIF-1α stabilization decouples β3-AR expression from oxygen levels further indicates that HIF-1 regulates the expression of the β3-AR gene in the retina. Bioinformatics predicted the presence of six HIF-1 binding sites (HBS #1-6) upstream and inside the mouse β3-AR gene. Among these, HBS #1 has been identified as the most suitable HBS for HIF-1 binding. Chromatin immunoprecipitation-qPCR demonstrated an effective binding of HIF-1 to HBS #1 indicating the existence of a physical interaction between HIF-1 and the β3-AR gene. The additional finding that β3-AR gene expression is concomitantly activated indicates the possibility that HIF-1 transactivates the β3-AR gene. Our results are indicative of β3-AR involvement in HIF-1-mediated response to hypoxia.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/299489

PBEsol/HSE Functional: A promising candidate for Vanadium dioxide (B) characterization
RSC ADVANCES
Autore/i: Mohebbi, Elaheh; Pavoni, Eleonora; Mencarelli, Davide; Stipa, Pierluigi; Pierantoni, Luca; Laudadio, Emiliano
Classificazione: 1 Contributo su Rivista
Abstract: A VO2(B) polymorph has been thoroughly investigated by means of density functional theory (DFT) calculations to evaluate the structure, Raman spectrum, cohesive energy, phonon band structure, an delectronic and optical properties. Among the computed Raman modes, eight of them have been assigned to the VO2(B) structure in full agreement with the corresponding experimental spectra. The minimized structure of the VO2(B) polymorph indicated the presence of negative frequencies in its phonon dispersion curves, confirming the dynamic instability of this material. Herein, the combination of generalized gradient approximation (GGA)/PBEsol with a hybrid HSE functional has been employed to perform ab initio calculations on VO2(B), since the conventional semi-local DFT calculations are believed to underestimate the band gap of materials. By considering the electronic structure calculations, for the first time, we found that the calibration of the PBEsol functional can efficiently model the metallic-like properties of VO2(B) with a band gap of 0.26 eV, while the corresponding electronic bandgap of VO2(B) based on the HSE functional possesses a larger band gap of 0.67 eV. The prediction of optical characteristics of VO2(B) indicated that the optical conductivity of VO2(B) lies in the infrared region of light. This work strongly suggests the combination of GGA/PBEsol with HSE hybrid functionals to carefully describe the physical properties of smart materials exploitable in electronics and optoelectronics applications. The nanostructure of VO2(B) looks promising for IR photodetectors and smart windows applications as a semiconductor material with excellent optical features. It is predicted that in the future VO2(B) will continue to expand the envelope of its capabilities because of its remarkable properties.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/308981

FTIR spectroscopy for determination of the raw materials used in wood pellet production
FUEL
Autore/i: Toscano, G.; Maceratesi, V.; Leoni, E.; Stipa, P.; Laudadio, E.; Sabbatini, S.
Classificazione: 1 Contributo su Rivista
Abstract: The research investigates the possibility of distinguishing pellet wood fuels using infrared spectroscopy. It has been applied Attenuated Total Reflectance – Fourier Transform InfraRed (ATR-FTIR) spectroscopy, deemed an analysis technique appropriate for detecting the chemical composition of materials, to determine woody components make up a wood pellet. Considering the large quantities of this solid biofuel on the market, it is necessary to guarantee the safety and traceability aspects of the product, as its origin and source, in addition to the quality parameters indicated by the ISO 17225-2 standards. In this study, a total of 98 samples of the most common wood used for European pellet production, have been selected and collected. This set of samples include also materials coming from the wood industry, as residues of the chemical process. Through clustering analysis Principal component Analysis (PCA) and Hierarchical Cluster Analysis (HCA) techniques applied to spectroscopic analyzer data, it has been seen that ATR-FTIR results provide information on wood pellet typology, hardwood and softwood, and pellet made by woody materials containing high quantity of chemical products like glues.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/297702

Microwave Detection Using Two-Atom-Thick Self-Switching Diodes Based on Quantum Simulations and Advanced Circuit Models
IEEE TRANSACTIONS ON MICROWAVE THEORY AND TECHNIQUES
Autore/i: Aldrigo, M.; Dragoman, M.; Pelagalli, N.; Laudadio, E.; Zappelli, L.; Iordanescu, S.; Vasilache, D.; Dinescu, A.; Pierantoni, L.; Stipa, P.; Mencarelli, D.
Classificazione: 1 Contributo su Rivista
Abstract: In this article, a two-atom-thick diode based on 2-D materials is presented for microwave detection. The diode consists of a molybdenum disulfide monolayer/graphene monolayer heterojunction transferred onto a silicon/silicon dioxide substrate and patterned by means of nanolithography techniques to obtain a geometrical self-switching diode. The interaction between the two monolayers gives rise to a double-stage device, which behaves as a back-to-back diode in the [-3, +3] V voltage range, and as a tunnel diode when exceeding +10 V. The heterojunction can be reproduced at the wafer scale, thanks to its CMOS compatibility and ease of fabrication, and it can be used efficiently as a microwave detector up to 10 GHz, with the best performance around the ISM 2.45-GHz band. Starting from advanced quantum simulations to predict the dc behavior of the single heterojunction-based channel, the diode was fabricated and fully characterized experimentally. Lastly, a rigorous equivalent circuit model is provided, which relies on the measured scattering parameters at high frequencies and allows treating the diode embedded into a coplanar waveguide line as a two-port lossy device. This way, the device can be exploited in circuit-based numerical tools for the design of complex microwave front ends.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/294141

Salt effects on mixed composition membranes containing an antioxidant lipophilic edaravone derivative: a computational-experimental study
ORGANIC & BIOMOLECULAR CHEMISTRY
Autore/i: Laudadio, Emiliano; Minnelli, Cristina; Mobbili, Giovanna; Sabbatini, Giulia; Stipa, Pierluigi; Rusciano, Dario; Galeazzi, Roberta
Classificazione: 1 Contributo su Rivista
Abstract: The protection of lipid membranes against oxidation avoids diseases associated with oxidative stress. As a strategy to contrast it, functionalized lipids with antioxidant activity are used to become part of membranes thus protecting them. For this purpose, a lipophilic edaravone derivative has been synthesized, adding a C18 saturated chain to the original structure. The antioxidant activity of C18-Edv has been demonstrated in our previous work. In this study, molecular dynamics simulations have been performed to define the effects of NaCl, MgCl2, KCl, and CaCl2 salts on a palmitoyl-oleoyl-sn-glycero-phosphocholine (POPC) lipid bilayer encapsulating C18-Edv. The results showed how different salts influence POPC lateral diffusion, and the movements of C18-Edv heads, which are antioxidant moieties, were correlate to the ability of C18-Edv molecules to protect membranes. MgCl2 showed a negative impact leading to C18-Edv clusterization and membrane stretching, while KCl and NaCl showed a moderate influence on the mixed lipid membrane structure. CaCl2 increased the exposure of the C18-Edv heads to the lipid–water interface, resulting in the salt with a higher propensity to guarantee protection against radicals in the aqueous phase. Finally, C18-Edv-POPC liposomes have been prepared following the simulation conditions, and then an experimental Oxygen Radical Absorbance Capacity (ORAC) assay has been performed to confirm the in silico predicted results.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/306581

Tuning curvature and phase behavior of monoolein bilayers by epigallocatechin-3-gallate: Structural insight and cytotoxicity
COLLOIDS AND SURFACES. B, BIOINTERFACES
Autore/i: Minnelli, C.; Moretti, P.; Laudadio, E.; Gerelli, Y.; Pigozzo, A.; Armeni, T.; Galeazzi, R.; Mariani, P.; Mobbili, G.
Classificazione: 1 Contributo su Rivista
Abstract: The use of glyceryl monooleate (GMO)-based nanoparticles has not yet been explored in overcoming the low bioavailability of Epigallocatechin-3-gallate (EGCG), a green tea polyphenol with a known anticancer activity. Since the inclusion of a guest molecule can affect the curvature and the supramolecular structure of fully hydrated GMO-based phase, the phase behavior of bulk and dispersed liquid crystalline systems containing EGCG were explored by Small Angle Neutron Scattering and X-Ray Diffraction experiments. Molecular Dynamic Simulations showed how the interaction of EGCG with polar heads of GMO strongly affects the curvature and packing of GMO phase. The EGCG encapsulation efficiency was determined in the nanodispersions and their size studied by Dynamic Light Scattering and Atomic Force Microscopy. A nanodispersed formulation has been optimized with a cytotoxic effect more than additive of GMO and EGCG.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/293264

Influence of a lipophilic edaravone on physical state and activity of antioxidant liposomes: An experimental and in silico study
COLLOIDS AND SURFACES. B, BIOINTERFACES
Autore/i: Minnelli, C.; Laudadio, E.; Fiorini, R.; Galeazzi, R.; Armeni, T.; Stipa, P.; Rusciano, D.; Mobbili, G.
Classificazione: 1 Contributo su Rivista
Abstract: The influence of a lipophilic derivative of Edaravone (C18Edv) on a POPC liposomal bilayer has been investigated by a combined computational-experimental approach. The order and hydration degree of three different systems composed by 10%, 20% and 40% in w/w percentage of C18Edv respect to POPC were investigated through Molecular Dynamics (MD) simulations and fluorescence spectroscopy experiments. Dynamic Light Scattering measurements showed how the presence of different amounts of C18EdV determines differences on liposome size and stability. The survey revealed that the content of lipophilic antioxidant tunes liposome rigidity and influences cellular uptake and antioxidant activity which are maximized for formulation containing 20% of C18Edv
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/293789

Glyoxalase 2: Towards a Broader View of the Second Player of the Glyoxalase System
ANTIOXIDANTS
Autore/i: Scire', Andrea Antonino; Cianfruglia, Laura; Minnelli, Cristina; Romaldi, Brenda; Laudadio, Emiliano; Galeazzi, Roberta; Antognelli, Cinzia; Armeni, Tatiana
Classificazione: 1 Contributo su Rivista
Abstract: Glyoxalase 2 is a mitochondrial and cytoplasmic protein belonging to the metallo-β-lactamase family encoded by the hydroxyacylglutathione hydrolase (HAGH) gene. This enzyme is the second enzyme of the glyoxalase system that is responsible for detoxification of the α-ketothaldehyde methylglyoxal in cells. The two enzymes glyoxalase 1 (Glo1) and glyoxalase 2 (Glo2) form the complete glyoxalase pathway, which utilizes glutathione as cofactor in eukaryotic cells. The importance of Glo2 is highlighted by its ubiquitous distribution in prokaryotic and eukaryotic organisms. Its function in the system has been well defined, but in recent years, additional roles are emerging, especially those related to oxidative stress. This review focuses on Glo2 by considering its genetics, molecular and structural properties, its involvement in post-translational modifications and its interaction with specific metabolic pathways. The purpose of this review is to focus attention on an enzyme that, from the most recent studies, appears to play a role in multiple regulatory pathways that may be important in certain diseases such as cancer or oxidative stress-related diseases.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/307801

Tailoring the Barrier Properties of PLA: A State-of-the-Art Review for Food Packaging Applications
POLYMERS
Autore/i: Marano, Stefania; Laudadio, Emiliano; Minnelli, Cristina; Stipa, Pierluigi
Classificazione: 1 Contributo su Rivista
Abstract: It is now well recognized that the production of petroleum-based packaging materials has created serious ecological problems for the environment due to their resistance to biodegradation. In this context, substantial research efforts have been made to promote the use of biodegradable films as sustainable alternatives to conventionally used packaging materials. Among several biopolymers, poly(lactide) (PLA) has found early application in the food industry thanks to its promising properties and is currently one of the most industrially produced bioplastics. However, more efforts are needed to enhance its performance and expand its applicability in this field, as packaging materials need to meet precise functional requirements such as suitable thermal, mechanical, and gas barrier properties. In particular, improving the mass transfer properties of materials to water vapor, oxygen, and/or carbon dioxide plays a very important role in maintaining food quality and safety, as the rate of typical food degradation reactions (i.e., oxidation, microbial development, and physical reactions) can be greatly reduced. Since most reviews dealing with the properties of PLA have mainly focused on strategies to improve its thermal and mechanical properties, this work aims to review relevant strategies to tailor the barrier properties of PLA-based materials, with the ultimate goal of providing a general guide for the design of PLA-based packaging materials with the desired mass transfer properties.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/304945

Phase Properties of Different HfO2 Polymorphs: A DFT-Based Study
CRYSTALS
Autore/i: Laudadio, Emiliano; Stipa, Pierluigi; Pierantoni, Luca; Mencarelli, Davide
Classificazione: 1 Contributo su Rivista
Abstract: Background: Hafnium Dioxide (HfO2) represents a hopeful material for gate dielectric thin films in the field of semiconductor integrated circuits. For HfO2, several crystal structures are possible, with different properties which can be difficult to describe in detail from an experimental point of view. In this study, a detailed computational approach has been shown to present a complete analysis of four HfO2 polymorphs, outlining the intrinsic properties of each phase on the basis of atomistic displacements. Methods: Density functional theory (DFT) based methods have been used to accurately describe the chemical physical properties of the polymorphs. Corrective Hubbard (U) semi-empirical terms have been added to exchange correlation energy in order to better reproduce the excited-state properties of HfO2 polymorphs. Results: the monoclinic phase resulted in the lowest cohesive energy, while the orthorhombic showed peculiar properties due to its intrinsic ferroelectric behavior. DFT + U methods showed the different responses of the four polymorphs to an applied field, and the orthorhombic phase was the least likely to undergo point defects as oxygen vacancies. Conclusions: The obtained results give a deeper insight into the differences in excited states phenomena in relation to each specific HfO2 polymorph.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/294525

Identification of a novel nitroflavone-based scaffold for designing mutant-selective EGFR tyrosine kinase inhibitors targeting T790M and C797S resistance in advanced NSCLC
BIOORGANIC CHEMISTRY
Autore/i: Minnelli, Cristina; Laudadio, Emiliano; Sorci, Leonardo; Sabbatini, Giulia; Galeazzi, Roberta; Amici, Adolfo; Semrau, Marta S.; Storici, Paola; Rinaldi, Samuele; Stipa, Pierluigi; Marcaccio, Massimo; Mobbili, Giovanna
Classificazione: 1 Contributo su Rivista
Abstract: The inhibition of the Epidermal Growth Factor (EGFR) represents one of the most promising strategies in non small cell lung cancer (NSCLC) therapy. The recently identified C797S mutation causes resistance of EGFRL858R/T790M against osimertinib, the latest approved third generation EGFR inhibitor. The identification of small molecules capable of selectively inhibiting the T790M mutations also in the late-onset C797S mutation is a desirable strategy and novel chemical structures might provide new insight in the overcoming resistance mechanisms. Here we report the identification of a novel mutant-selective privileged molecular core; guided by a structure-based drug design, a flavone skeleton has been rationally modified, and a virtual library generated. Reversible EGFR inhibitors targeting both L858R/T790M and L858R/T790M/C797S mutations with a higher affinity with respect to the wild type one are discovered via a three-track virtual screening. Selected hits were synthesized and tested in an activity-based enzyme assay against wild-type EGFR, L858R/T790M, as well as L858R/T790M/C797S. The results showed that a nitroflavone-based compound inhibits the phosphorylation of EGFR mutants at low-micromolar concentration showing selectivity over the wild type ones. Structurally similar flavone analogues have been synthesized and the following inhibition assays underlied the importance of both the presence and position of the nitrophenoxy moiety.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/308602

Prediction of drug-carrier interactions of PLA and PLGA drug-loaded nanoparticles by molecular dynamics simulations
EUROPEAN POLYMER JOURNAL
Autore/i: Stipa, Pierluigi; Marano, Stefania; Galeazzi, Roberta; Minnelli, Cristina; Mobbili, Giovanna; Laudadio, Emiliano
Classificazione: 1 Contributo su Rivista
Abstract: terestdue to their potential as an ideal non-toxic vehicle for the delivery of active compounds in a controlled andtargeted manner. However, at the stage of academic and industrial development, the lack of regulatory instructionsfor the assessment and characterization of those nanometric materials is considerably delaying theirclinical success if compared to other macroscopic systems (i.e. microparticles). In fact, owing to their highsurface area to volume ratio, unwanted interactions between nanoparticles and biological systems may occur,leading to unexpected toxicity. In addition, knowledge of drug-polymer interactions is compulsory, as they candirectly affect many fundamental properties, such as the drug-loading ability, nanoparticle size, the drug physicalstate and stability, as well as the actual drug release profile.In this context, computational methods able to rapidly predict the binding and dynamics between drugmolecule and its carrier, and between the carrier and biological systems, are highly desirable to minimize theinvestment in drug design and development. In this study a full atomistic molecular dynamics simulationapproach was validated to investigate biomolecular behaviour of poly (lactic acid) (PLA) and poly (lactic-coglycolicacid) (PLGA) as nanoparticulate drug delivery systems. Both polymer systems have been firstly investigatedwithout drugs to better observe their tendency to interact with aqueous solution, which represents a crucial point for drug delivery systems. Subsequently, simulations were run after the incorporation of drugs. Paracetamol, Prednisolone, and Isoniazid were chosen as model drugs in relation to their different affinity with lipids. Specific interactions between polymers and drugs were considered, and a direct comparison between computational results and experimental evidences found in literature was carried out.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/287681

Amidinoquinoxaline-Based Nitrones as Lipophilic Antioxidants
ANTIOXIDANTS
Autore/i: Gruber, Nadia; Orelli, Liliana; Minnelli, Cristina; Mangano, Luca; Laudadio, Emiliano; Mobbili, Giovanna; Stipa, Pierluigi
Classificazione: 1 Contributo su Rivista
Abstract: The potential of nitrones (N-oxides) as therapeutic antioxidants is due to their ability to counteract oxidative stress, mainly attributed to their action as radical scavengers toward C- and Ocentered radicals. Among them, nitrones from the amidinoquinoxaline series resulted in interesting derivatives, due to the ease with which it is possible to introduce proper substituents within their structure in order to modulate their lipophilicity. The goal is to obtain lipophilic antioxidants that are able to interact with cell membranes and, at the same time, enough hydrophilic to neutralize those radicals present in a water compartment. In this work, the antioxidant efficacy of a series of amidinoquinoxaline nitrones has been evaluated regarding the oxidation of 2-deoxyribose and lipid peroxidation. The results have been rationalized on the basis of the different possible mechanisms involved, depending on some of their properties, such as lipophilicity, the ability to scavenge free radicals, and to undergo single electron transfer (SET) reactions.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/291464

Molecular dynamics simulations of quinine encapsulation into biodegradable nanoparticles: A possible new strategy against Sars-CoV-2
EUROPEAN POLYMER JOURNAL
Autore/i: Stipa, Pierluigi; Marano, Stefania; Galeazzi, Roberta; Minnelli, Cristina; Laudadio, Emiliano
Classificazione: 1 Contributo su Rivista
Abstract: A new coronavirus disease, SARS-CoV-2, has spread into a global pandemic in December 2019. Since no specific therapeutic drugs for treating COVID-19 have been approved by FDA, recent studies suggest that the known antimalarial quinine and its derivatives (chloroquine and hydroxychloroquine) inhibit receptor binding of the viral particles and inhibits the strong “cytokine storm”, which is the main cause of death among infected patients. In particular, the natural alkaloid quinine has shown to possess a better safety profile and greater tolerability compared to its derivatives. Dosage optimization of quinine is still necessary as the currently available dosage forms have controversial pharmacokinetics and safety profiles. Therefore, repurposing quinine dosage forms to improve its pharmacokinetics and safety profile may be necessary to support its use against SARS-CoV-2. In this context, biodegradable/biocompatible polymeric nanoparticles may provide a safe site-specific and controlled quinine delivery, reducing the frequency of drug administration and the dose. In this study, a full atomistic molecular dynamics simulation approach has been used to investigate the use of poly-(glycolic acid) and poly-(lactic acid) and their copolymer poly-(lactic-co-glycolic acid) as potential delivery systems for lipophilic quinine to get insights into the mechanism of quinine encapsulation and release at the atomic/molecular level.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/291646

Insights into the Antioxidant Mechanism of Newly Synthesized Benzoxazinic Nitrones: In Vitro and In Silico Studies with DPPH Model Radical
ANTIOXIDANTS
Autore/i: Marano, Stefania; Minnelli, Cristina; Ripani, Lorenzo; Marcaccio, Massimo; Laudadio, Emiliano; Mobbili, Giovanna; Amici, Adolfo; Armeni, Tatiana; Stipa, Pierluigi
Classificazione: 1 Contributo su Rivista
Abstract: Synthetic nitrone spin-traps are being explored as therapeutic agents for the treatment of a wide range of oxidative stress-related pathologies, including but not limited to stroke, cancer, cardiovascular, and neurodegenerative diseases. In this context, increasing efforts are currently being made to the design and synthesis of new nitrone-based compounds with enhanced efficacy. The most researched nitrones are surely the ones related to α-phenyl-tert-butylnitrone (PBN) and 5,5- dimethyl-1-pyrroline N-oxide (DMPO) derivatives, which have shown to possess potent biological activity in many experimental animal models. However, more recently, nitrones with a benzoxazinic structure (3-aryl-2H-benzo[1,4]oxazin-N-oxides) have been demonstrated to have superior antioxidant activity compared to PBN. In this study, two new benzoxazinic nitrones bearing an electron- withdrawing methoxycarbonyl group on the benzo moiety (in para and meta positions respect to the nitronyl function) were synthesized. Their in vitro antioxidant activity was evaluated by two cellular-based assays (inhibition of AAPH-induced human erythrocyte hemolysis and cell death in human retinal pigmented epithelium (ARPE-19) cells) and a chemical approach by means of the α,α-diphenyl-β-picrylhydrazyl (DPPH) scavenging assay, using both electron paramagnetic resonance (EPR) spectroscopy and UV spectrophotometry. A computational approach was also used to investigate their potential primary mechanism of antioxidant action, as well as to rationalize the effect of functionalization on the nitrones reactivity toward DPPH, chosen as model radical in this study. Further insights were also gathered by exploring the nitrone electrochemical properties via cyclic voltammetry and by studying their kinetic behavior by means of EPR spectroscopy. Results showed that the introduction of an electron-withdrawing group in the phenyl moiety in the para position significantly increased the antioxidant capacity of benzoxazinic nitrones both in cell and cell-free systems. From the mechanistic point of view, the calculated results closely matched the experimental findings, strongly suggesting that the H-atom transfer (HAT) is likely to be the primary mechanism in the DPPH quenching.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/291465

Berberine derivatives as pseudomonas aeruginosa mexxy-oprm inhibitors: Activity and in silico insights
MOLECULES
Autore/i: Giorgini, G.; Mangiaterra, G.; Cedraro, N.; Laudadio, E.; Sabbatini, G.; Cantarini, M.; Minnelli, C.; Mobbili, G.; Frangipani, E.; Biavasco, F.; Galeazzi, R.
Classificazione: 1 Contributo su Rivista
Abstract: The natural alkaloid berberine has been demonstrated to inhibit the Pseudomonas aeruginosa multidrug efflux system MexXY-OprM, which is responsible for tobramycin extrusion by binding the inner membrane transporter MexY. To find a structure with improved inhibitory activity, we compared by molecular dynamics investigations the binding affinity of berberine and three aromatic substituents towards the three polymorphic sequences of MexY found in P. aeruginosa (PAO1, PA7, and PA14). The synergy of the combinations of berberine or berberine derivatives/tobramycin against the same strains was then evaluated by checkerboard and time-kill assays. The in silico analysis evidenced different binding modes depending on both the structure of the berberine derivative and the specific MexY polymorphism. In vitro assays showed an evident MIC reduction (32-fold and 16-fold, respectively) and a 2–3 log greater killing effect after 2 h of exposure to the combinations of 13-(2-methylbenzyl)-and 13-(4-methylbenzyl)-berberine with tobramycin against the tobramycin-resistant strain PA7, a milder synergy (a 4-fold MIC reduction) against PAO1 and PA14, and no synergy against the ΔmexXY strain K1525, confirming the MexY-specific binding and the computational results. These berberine derivatives could thus be considered new hit compounds to select more effective berberine substitutions and their common path of interaction with MexY as the starting point for the rational design of novel MexXY-OprM inhibitors.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/293785

The Natural Alkaloid Berberine Can Reduce the Number of Pseudomonas aeruginosa Tolerant Cells
JOURNAL OF NATURAL PRODUCTS
Autore/i: Mangiaterra, G.; Cedraro, N.; Laudadio, E.; Minnelli, C.; Citterio, B.; Andreoni, F.; Mobbili, G.; Galeazzi, R.; Biavasco, F.
Classificazione: 1 Contributo su Rivista
Abstract: The eradication of recurrentPseudomonas aeruginosa(PA) lung infection in cystic fibrosis (CF) patients may be hampered by the development of persistent bacterial forms, which can tolerate antibiotics through efflux pump overexpression. After demonstrating the efflux pump inhibitory effect of the alkaloid berberine on the PA MexXY-OprM efflux pump, in this study, we tested its ability (80/320 μg/mL) to enhance tobramycin (20xMIC/1000xMIC) activity against PA planktonic/biofilm cultures. Preliminary investigations of the involvement of MexY in PA tolerance to tobramycin treatment, performed on the isogenic pair PA K767 (wild type)/K1525 (ΔmexY) growing in planktonic and biofilm cultures, demonstrated that the ΔmexYmutant K1525 produced a lower (100 and 10 000 times, respectively) amount of tolerant cells than that of the wild type. Next, we grew broth cultures of PAO1, PA14, and 20 PA clinical isolates (of which 13 were from CF patients) in the presence of 20xMIC tobramycin with and without berberine 80 μg/mL. Accordingly, most strains showed a greater (from 10- to 1000-fold) tolerance reduction in the presence of berberine. These findings highlight the involvement of the MexXY-OprM system in the tobramycin tolerance of PA and suggest that berberine may be used in new valuable therapeutic combinations to counteract persister survival.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/293786

Effect of epigallocatechin-3-gallate on egfr signaling and migration in non-small cell lung cancer
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Autore/i: Minnelli, C.; Cianfruglia, L.; Laudadio, E.; Mobbili, G.; Galeazzi, R.; Armeni, T.
Classificazione: 1 Contributo su Rivista
Abstract: The epidermal growth factor receptor (EGFR) is one of the most well-studied molecular targets in non-small cell lung cancer (NSCLC) and tyrosine kinase inhibitors have been shown to be effective in the treatment of advanced NSCLC. Nevertheless, the efficacy of tyrosine kinase inhibitors could be compromised by additional mutations in EGFR and compensatory activations of other pathways. Epigallocatechin-3-gallate (EGCG), the main bioactive molecule in green tea, acts as a tyrosine kinase inhibitor toward cancer cells overexpressing EGFR (wild-type). However, little information has been reported on the effect of EGCG on EGFR with activating mutations. In this study, we evaluated the ability of EGCG to inhibit EGFR signaling activation in three different NSCLC cell lines containing wild-type EGFR or EGFR with additional mutations. The effect on proliferation, apoptosis, migration, and vinculin expression was then studied. Overall, our results demonstrate that EGCG polyphenol inhibits cell proliferation and migration in NSCLC cell lines, although with different efficacy and mechanisms. These data may be of interest for an evaluation of the use of EGCG as an adjunct to NSCLC therapies.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/293787

Acetylshikonin isolated from Lithospermum erythrorhizon roots inhibits dihydrofolate reductase and hampers autochthonous mammary carcinogenesis in Δ16HER2 transgenic mice
PHARMACOLOGICAL RESEARCH
Autore/i: Wang, J.; Iannarelli, R.; Pucciarelli, S.; Laudadio, E.; Galeazzi, R.; Giangrossi, M.; Falconi, M.; Cui, L.; Navia, A. M.; Buccioni, M.; Marucci, G.; Tomassoni, D.; Serini, L.; Sut, S.; Maggi, F.; Dall'Acqua, S.; Marchini, C.; Amici, A.
Classificazione: 1 Contributo su Rivista
Abstract: Breast cancer (BC) is the most common cancer in women and, among different BC subtypes, triple negative (TN) and human epidermal growth factor receptor 2 (HER2)-positive BCs have the worst prognosis. In this study, we investigated the anticancer activity of the root ethanolic and hexane extracts from Lithospermum erythrorhizon, a traditional Chinese herbal medicine known also as tzu ts'ao or tzu-ken, against in vitro and in vivo models of TNBC and HER2-positive BC. Treatment with L. erythrorhizon root extracts resulted in a dose-dependent inhibition of BC cell viability and in a significant reduction of the growth of TNBC cells transplanted in syngeneic mice. Acetylshikonin, a naphthoquinone, was identified as the main bioactive component in extracts and was responsible for the observed antitumor activity, being able to decrease BC cell viability and to interfere with autochthonous mammary carcinogenesis in Δ16HER2 transgenic mice. Acetylshikonin anticancer effect depends on its ability to act as a potent inhibitor of dihydrofolate reductase (DHFR), to down-regulate key mediators governing cancer growth and progression, such as HER2, Src and STAT3, and to induce apoptosis by caspase-3 activation. The accumulation of acetylshikonin in blood samples as well as in brain, kidney, liver and tumor tissues was also investigated by liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS) highlighting that L. erythrorhizon treatment is effective in delivering the active compound into the target tissues. These results provide evidence that L. erythrorhizon extract and in particular its main component acetylshikonin are effective against aggressive BC subtypes and reveal new acetylshikonin mechanisms of action.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/285410

Role of tobramycin in the induction and maintenance of viable but non-culturable pseudomonas aeruginosa in an in vitro biofilm model
ANTIBIOTICS
Autore/i: Mangiaterra, G.; Cedraro, N.; Vaiasicca, S.; Citterio, B.; Galeazzi, R.; Laudadio, E.; Mobbili, G.; Minnelli, C.; Bizzaro, D.; Biavasco, F.
Classificazione: 1 Contributo su Rivista
Abstract: The recurrence of Pseudomonas aeruginosa (PA) biofilm infections is a major issue in cystic fibrosis (CF) patients. A pivotal role is played by the presence of antibiotic-unresponsive persisters and/or viable but non-culturable (VBNC) forms, whose development might be favored by subinhibitory antibiotic concentrations. The involvement of tobramycin and ciprofloxacin, widely used to treat CF PA lung infections, in the abundance of VBNC cells was investigated in PA biofilms models. In vitro biofilms of the laboratory strain PAO1-N and the clinical strain C24 were developed and starved by subculture for 170 days in a non-nutrient (NN) broth, unsupplemented or supplemented with one-quarter minimal inhibitory concentration (MIC) of tobramycin or ciprofloxacin. VBNC cells abundance, estimated as the difference between total live (detected by qPCR and flow cytometry) and colony forming unit (CFU) counts, showed a strain-and drug-specific pattern. A greater and earlier abundance of VBNC PAO1-N cells was detected in all conditions. Exposure of the C24 strain to NN and NN + ciprofloxacin induced only a transient VBNC subpopulation, which was more abundant and stable until the end of the experiment in tobramycin-exposed biofilms. The same response to tobramycin was observed in the PAO1-N strain. These findings suggest that low tobramycin concentrations might contribute to PA infection recurrence by favoring the development of VBNC forms.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/285412

Encapsulation of a neutral molecule into a cationic clay material: Structural insight and cytotoxicity of resveratrol/layered double hydroxide/BSA nanocomposites
NANOMATERIALS
Autore/i: Minnelli, C.; Laudadio, E.; Galeazzi, R.; Barucca, G.; Notarstefano, V.; Cantarini, M.; Armeni, T.; Mobbili, G.
Classificazione: 1 Contributo su Rivista
Abstract: Resveratrol (RES) is a stilbenoid polyphenol with interesting antitumor activity compromised by its poor solubility and bioavailability; thus, new approaches are necessary to improve its therapeutic effectiveness. In the present study, bovine serum albumin coated layered double hydroxide (LDH–BSA) was employed to encapsulate RES in order to overcome the above-mentioned usage limits. To evaluate the feasibility of neutral RES complexation with cationic LDH, we carried out molecular dynamics simulation in order to predict its structure and stability. In the supramolecular complex formed with LDH, RES disposes itself in the interlamellar region of LDH where it is stabilized by intermolecular interactions. The physico-chemical characteristics of the resulting nanocomplexes were studied by X-ray powder diraction, transmission electron microscopy, and attenuated total reflection Fourier transform infrared spectroscopy. The encapsulation efficiency and drug release studies were also performed. The combined experimental and computational approach were highly effective in giving insight into the interaction mode of the neutral RES with the charged LDH. Finally, the nanohybrid’s anticancer ability was evaluated in human lung cancer cell line (A549) resulting in higher activity with respect to bare RES. Overall, the results showed that the nanocomposites are suitable for biomedical applications as delivery agents of RES.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/273148

Cholesterol-mediated oligomerization pathways of serotonin G-coupled receptor 5-HT2C
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
Autore/i: Massaccesi, Luca; Laudadio, Emiliano; Mobbili, Giovanna; Minnelli, Cristina; Galeazzi, Roberta
Classificazione: 1 Contributo su Rivista
Abstract: Serotonin (5-HT) receptors have been shown to homodimerize and heterodimerize with other G protein-coupled receptors (GPCRs), although the details of this process have not yet been elucidated. Here we use coarse-grained molecular dynamics on monomeric 5-HT2C receptors to predict the transmembrane (TM) helices involved in such associations. All these simulations were carried out both in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayers and in mixed composition POPC-Cholesterol ones, to show whether the presence of cholesterol could directly influence and drive the dimeric association. The goal is to get insights on the self-assembly pathway leading to GPCRs 5-HT2C oligomerization, which is supposed to be the basis of its constitutional activity. From the analysis of the molecular dynamics trajectories, we observed the formation of 5-HT2C oligomers through self-assembly and we identified the main domains involved in the receptor dimerization. In particular, dimers and oligomers from the two different environments show TM4-TM5 and TM1-TM7-H8 as the preferential dimerization interfaces. Nevertheless, substantial differences arise for oligomers in POPC and in POPC-Chol membranes: in POPC-Chol the variability of dimers interfaces is strictly limited to the TM1-TM7-H8 and TM4-TM5 interfaces and the dimorphism depends on cholesterol that directly participates in its formation. These results are in agreement with both experimental evidences and other computational studies conducted on other GPCRs oligomerization.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/282435

Monoalkylated Epigallocatechin-3-gallate (C18-EGCG) as Novel Lipophilic EGCG Derivative: Characterization and Antioxidant Evaluation
ANTIOXIDANTS
Autore/i: Minnelli, Cristina; Galeazzi, Roberta; Laudadio, Emiliano; Amici, Adolfo; Rusciano, Dario; Armeni, Tatiana; Cantarini, Mattia; Stipa, Pierluigi; Mobbili, Giovanna
Classificazione: 1 Contributo su Rivista
Abstract: Epigallocatechin-3-gallate (EGCG) has the highest antioxidant activity compared to the others catechins of green tea. However, the beneficial eects are mainly limited by its poor membrane permeability. A derivatization strategy to increase the EGCG interaction with lipid membranes is considered as one feasible approach to expand its application in lipophilic media, in particular the cellular absorption. At this purpose the hydrophilic EGCG was modified by inserting an aliphatic C18 chain linked to the gallate ring by an ethereal bond, the structure determined by NMR (Nuclear Magnetic Resonance) and confirmed by Density Functional Theory (DFT) calculations. The in vitro antioxidant activity of the mono-alkylated EGCG (C18-EGCG) was studied by the DPPH and Thiobarbituric Acid Reactive Substances (TBARS) assays, and its ability to protect cells towards oxidative stress was evaluated in Adult Retinal Pigmented Epithelium (ARPE-19) cells. Molecular Dynamics (MD) simulation and liposomal/buer partition were used to study the interaction of the modified and unmodified antioxidants with a cell membrane model: the combined experimental-in silico approach shed light on the higher anity of C18-EGCG toward lipid bilayer. Although the DPPH assay stated that the functionalization decreases the EGCG activity against free radicals, from cellular experiments it resulted that the lipid moiety increases the antioxidant protection of the new lipophilic derivative.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/275132

Efficient and versatile modeling of mono-and multi-layer MoS2 field effect transistor
ELECTRONICS
Autore/i: Pelagalli, N.; Laudadio, E.; Stipa, P.; Mencarelli, D.; Pierantoni, L.
Classificazione: 1 Contributo su Rivista
Abstract: Two-dimensional (2D) materials with intrinsic atomic-level thicknesses are strong candidates for the development of deeply scaled field-effect transistors (FETs) and novel device architectures. In particular, transition-metal dichalcogenides (TMDCs), of which molybdenum disulfide (MoS2) is the most widely studied, are especially attractive because of their non-zero bandgap, mechanical flexibility, and optical transparency. In this contribution, we present an efficient full-wave model of MoS2-FETs that is based on (1) defining the constitutive relations of the MoS2 active channel, and (2) simulating the 3D geometry. The former is achieved by using atomistic simulations of the material crystal structure, the latter is obtained by using the solver COMSOL Multiphysics. We show examples of FET simulations and compare, when possible, the theoretical results to the experimental from the literature. The comparison highlights a very good agreement.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/284800

Microwave applications of zirconium-doped hafnium oxide ferroelectrics: From nanoscale calculations up to experimental results
IEEE MTT-S International Microwave Symposium Digest
Autore/i: Aldrigo, M.; Dragoman, M.; Laudadio, E.; Iordanescu, S.; Modreanu, M.; Povey, I. M.; Nastase, F.; Vulpe, S.; Stipa, P.; Di Donato, A.; Pierantoni, L.; Mencarelli, D.
Editore: Institute of Electrical and Electronics Engineers Inc.
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Abstract: In this paper, a systematic approach is reported for the electrical properties investigation of an emerging new class of materials for microwave applications, namely zirconium-doped hafnium oxide (HfZrO) ferroelectrics. Starting from atomistic simulations that take into account both structural and spectroscopic data to determine the interatomic potentials, the dielectric constant for the orthorhombic phase of HfZrO ferroelectrics has been extracted. By employing well-established microwave characterization techniques, the tunability of both effective permittivity and loss tangent of HfZrO for a low DC bias voltage of ±5 V has been verified experimentally. Finally, two microwave applications of thin-film (6-nm-thick) HfZrO-based ferroelectrics have been explored, namely an interdigitated capacitor-like phase shifter and a phased antenna array made of two patch elements working at 2.55 GHz, able to steer its beam of 25° for an applied bias of only ±1 V. These results demonstrate the potential impact that ferroelectric-based microwave circuits with tunable characteristics will have in the future telecommunications systems and, as well, the importance of a rigorous approach for their full chemical, physical and electromagnetic characterization.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/284943

Conformational Insight on WT- and Mutated-EGFR Receptor Activation and Inhibition by Epigallocatechin-3-Gallate: Over a Rational Basis for the Design of Selective Non-Small-Cell Lung Anticancer Agents
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Autore/i: Minnelli, Cristina; Laudadio, Emiliano; Mobbili, Giovanna; Galeazzi, Roberta
Classificazione: 1 Contributo su Rivista
Abstract: Non-small cell lung cancer (NSCLC) represents a dicult condition to treat, due to epidermal growth factor receptor (EGFR) kinase domain mutations, which lead to ligand-independent phosphorylation. Deletion of five amino acids (ELREA) in exon 19 and mutational change from leucine to arginine at position 858 (L858R) are responsible for tyrosine kinase domain aberrant activation. These two common types of EGFR-mutated forms are clinically associated with high response with Tyrosine Kinase Inhibitors (TKI); however, the secondary T790M mutation within the Tyrosine Kinase Domain (TKD) determines a resistance to these EGFR-TKIs. Using molecular dynamic simulation (MD), the present study investigated the architectural changes of wild-type and mutants EGFR’s kinase domains in order to detect any conformational dierences that could be associated with a constitutively activated state and thus to evaluate the dierences between the wild-type and its mutated forms. In addition, in order to evaluate to which extent the EGFR mutations aect its inhibition, Epigallocatechin 3-Gallate (EGCG) and Erlotinib (Erl), known EGFR-TKI, were included in our study. Their binding modes with the EGFR-TK domain were elucidated and the binding dierences between EGFR wild-type and the mutated forms were evidenced. The aminoacids mutations directly influence the binding anity of these two inhibitors, resulting in a dierent ecacy of Erl and EGCG inhibition. In particular, for the T790M/L858R EGFR, the binding modes of studied inhibitors were compromised by aminoacidic substitution confirming the experimental findings. These results may be useful for novel drug design strategies targeting the dimerization domain of the EGFR mutated forms, thus preventing receptor activation.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/275131

Synthesis, characterization and antioxidant properties of a new lipophilic derivative of edaravone
ANTIOXIDANTS
Autore/i: Minnelli, C.; Laudadio, E.; Galeazzi, R.; Rusciano, D.; Armeni, T.; Stipa, P.; Cantarini, Mattia; Mobbili, G.
Classificazione: 1 Contributo su Rivista
Abstract: As part of a program aimed to obtain antioxidants able to interact with cell membrane, edaravone (EdV, 3-methyl-1-phenyl-2-pyrazolin-5-one), a well-known free radical scavenger, has been modified by alkylation at its allylic position (4) with a C-18 hydrocarbon chain, and the increased lipophilicity has been determined towards the interaction with liposomes. The obtained derivative has been studied by means of density functional theory (DFT) methods in order to characterize its lowest energy conformers and predict its antioxidant properties with respect to the parent compound EdV. The in vitro antioxidant activity of C18-edaravone was studied by means of the α,α-diphenyl-β-picrylhydrazyl (DPPH) assay and in lipid peroxidation experiments performed on artificial lipid membranes using water-soluble as well as lipid-soluble radical initiators. Moreover, since oxidative stress is involved in numerous retinal degenerative diseases, the ability of C18-edaravone to contrast 2,2-azobis (2-amidinopropane hydrochloride) (AAPH)-induced cell death was assessed in adult retinal pigmented epithelium (ARPE-19) cells. Overall, the results demonstrated that the newly synthesized molecule has a high affinity for lipid membrane, increasing the efficacy of the unmodified edaravone under stress conditions.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/269345

Insights into the Molecular Mechanisms of Eg5 Inhibition by (+)-Morelloflavone
PHARMACEUTICALS
Autore/i: Ogunwa, Tomisin Happy; Laudadio, Emiliano; Galeazzi, Roberta; Miyanishi, Takayuki
Classificazione: 1 Contributo su Rivista
Abstract: (+)-Morelloflavone (MF) is an antitumor biflavonoid that is found in the Garcinia species. Recently, we reported MF as a novel inhibitor of ATPase and microtubules-gliding activities of the kinesin spindle protein (Eg5) in vitro. Herein, we provide dynamical insights into the inhibitory mechanisms of MF against Eg5, which involves binding of the inhibitor to the loop5/α2/α3 allosteric pocket. Molecular dynamics simulations were carried out for 100 ns on eight complexes: Eg5-Adenosine diphosphate (Eg5-ADP), Eg5-ADP- S -trityl-l-cysteine (Eg5-ADP-STLC), Eg5-ADP-ispinesib, Eg5-ADP-MF, Eg5-Adenosine triphosphate (Eg5-ATP), Eg5-ATP-STLC, Eg5-ATP-ispinesib, and Eg5-ATP-MF complexes. Structural and energetic analyses were done using Umbrella sampling, Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) method, GROMACS analysis toolkit, and virtual molecular dynamics (VMD) utilities. The results were compared with those of the known Eg5 inhibitors; ispinesib, and STLC. Our data strongly support a stable Eg5-MF complex, with significantly low binding energy and reduced flexibility of Eg5 in some regions, including loop5 and switch I. Furthermore, the loop5 Trp127 was trapped in a downward position to keep the allosteric pocket of Eg5 in the so-called "closed conformation", comparable to observations for STLC. Altered structural conformations were also visible within various regions of Eg5, including switch I, switch II, α2/α3 helices, and the tubulin-binding region, indicating that MF might induce modifications in the Eg5 structure to compromise its ATP/ADP binding and conversion process as well as its interaction with microtubules. The described mechanisms are crucial for understanding Eg5 inhibition by MF.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/266043

Depth Distribution of Spin-Labeled Liponitroxides within Lipid Bilayers: A Combined EPR and Molecular Dynamics Approach
ACS OMEGA
Autore/i: Laudadio, Emiliano; Galeazzi, Roberta; Mobbili, Giovanna; Minnelli, Cristina; Barbon, Antonio; Bortolus, Marco; Stipa, Pierluigi
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/265831

A novel 3'-tRNAGlu-derived fragment acts as a tumor suppressor in breast cancer by targeting nucleolin
FASEB JOURNAL
Autore/i: Falconi, M.; Giangrossi, M.; Zabaleta, M. E.; Wang, J.; Gambini, V.; Tilio, M.; Bencardino, D.; Occhipinti, S.; Belletti, B.; Laudadio, E.; Galeazzi, R.; Marchini, C.; Amici, A.
Classificazione: 1 Contributo su Rivista
Abstract: RNA-derived fragments (tRFs) have been defined as a novel class of small noncoding RNAs. tRFs have been reported to be deregulated in cancer, but their biologic function remains to be fully understood. We have identified a new tRF (named tRF3E), derived from mature tRNAGlu, that is specifically expressed in healthy mammary glands but not in breast cancer (BC). Consistently, tRF3E levels significantly decrease in the blood of patients with epidermal growth factor receptor 2 (HER2)-positive BC reflecting tumor status (control > early cancer > metastatic cancer). tRF3E down-regulation was recapitulated in Δ16HER2 transgenic mice, representing a BC preclinical model. Pulldown assays, used to search for proteins capable to selectively bind tRF3E, have shown that this tRF specifically interacts with nucleolin (NCL), an RNA-binding protein overexpressed in BC and able to repress the translation of p53 mRNA. The binding properties of NCL-tRF3E complex, predicted in silico and analyzed by EMSA assays, are congruent with a competitive displacement of p53 mRNA by tRF3E, leading to an increased p53 expression and consequently to a modulation of cancer cell growth. Here, we provide evidence that tRF3E plays an important role in the pathogenesis of BC displaying tumor-suppressor functions through a NCL-mediated mechanism
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/273149

Early impairment of epigenetic pattern in neurodegeneration: Additional mechanisms behind pyrethroid toxicity
EXPERIMENTAL GERONTOLOGY
Autore/i: Bordoni, L.; Nasuti, C.; Fedeli, D.; Galeazzi, R.; Laudadio, E.; Massaccesi, L.; Lopez-Rodas, G.; Gabbianelli, R.
Classificazione: 1 Contributo su Rivista
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/267206

Side Effects of Curcumin: Epigenetic and Antiproliferative Implications for Normal Dermal Fibroblast and Breast Cancer Cells
ANTIOXIDANTS
Autore/i: Cianfruglia, Laura; Minnelli, Cristina; Laudadio, Emiliano; Scirè, Andrea; Armeni, Tatiana
Classificazione: 1 Contributo su Rivista
Abstract: Curcumin is a yellow-orange pigment obtained from the plant Curcuma longa, which is known to exert beneficial effects in several diseases, including cancer. However, at high doses, it may produce toxic and carcinogenic effects in normal cells. In this context, we studied the effects of curcumin on normal human dermal fibroblast (HDF) cells and breast cancer cells (MCF7).
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/270288

Natural Alkaloid Berberine Activity against Pseudomonas aeruginosa MexXY-Mediated Aminoglycoside Resistance: In Silico and in Vitro Studies
JOURNAL OF NATURAL PRODUCTS
Autore/i: Laudadio, Emiliano; Cedraro, Nicholas; Mangiaterra, Gianmarco; Citterio, Barbara; Mobbili, Giovanna; Minnelli, Cristina; Bizzaro, Davide; Biavasco, Francesca; Galeazzi, Roberta
Classificazione: 1 Contributo su Rivista
Abstract: The multidrug efflux system MexXY-OprM, inside the resistance-nodulation-division family, is a major determinant of aminoglycoside resistance in Pseudomonas aeruginosa. In the fight aimed to identify potential efflux pump inhibitors among natural compounds, the alkaloid berberine emerged as a putative inhibitor of MexXY-OprM. In this work, we elucidated its interaction with the extrusor protein MexY and assessed its synergistic activity with aminoglycosides. In particular, we built an in silico model for the MexY protein in its trimeric association using both AcrB ( E. coli) and MexB ( P. aeruginosa) as 3D templates. This model has been stabilized in the bacterial cytoplasmic membrane using a molecular dynamics approach and used for ensemble docking to obtain the binding site mapping. Then, through dynamic docking, we assessed its binding affinity and its synergism with aminoglycosides focusing on tobramycin, which is widely used in the treatment of pulmonary infections. In vitro assays validated the data obtained: the results showed a 2-fold increase of the inhibitory activity and 2-4 log increase of the killing activity of the association berberine-tobramycin compared to those of tobramycin alone against 13/28 tested P. aeruginosa clinical isolates. From hemolytic assays, we preliminarily assessed berberine's low toxicity.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/267855

A Poloxamer-407 modified liposome encapsulating epigallocatechin-3-gallate in the presence of magnesium: Characterization and protective effect against oxidative damage
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Autore/i: Minnelli, C.; Moretti, P.; Fulgenzi, G.; Mariani, P.; Laudadio, E.; Armeni, T.; Galeazzi, R.; Mobbili, G.
Classificazione: 1 Contributo su Rivista
Abstract: Epigallocatechin-3-gallate (EGCG) is a polyphenolic catechin from green tea, well known for being bioactive in age-associated pathologies where oxidative stress plays a preeminent role. The activity of this molecule is however contrasted by its high chemical and metabolic instability that determines a poor concentration of the antioxidant within the biological system after administration. In order to protect the molecule and increase its delivery efficiency, we have encapsulated EGCG inside anionic liposomes made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine and cholesteryl hemisuccinate. To maximize EGCG internalization, magnesium salt was added in the preparation. However stable nanodispersions suitable for drug delivery were obtained only after treatment with Poloxamer-407, a polyethylene–propylene glycol copolymer. The structural and morphological properties of the produced dispersion were studied by X-ray diffraction, which showed a multilamellar structure even after EGCG addition and an ordering effect of Poloxamer-407; Dynamic Light Scattering demonstrated serum stability of the liposomes. The characterization was completed by evaluating both encapsulation efficiency (100%, in the final formulation) and in vitro EGCG release. Since oxidative stress is involved in numerous retinal degenerative diseases, such as age-related macular degeneration, the ability of these liposomes to contrast H2O2-induced cell death was assessed in human retinal cells. Morphological changes at the subcellular level were analyzed by Transmission Electron Microscopy, which showed that mitochondria were better preserved in cells treated with liposomes then those treated with free EGCG. In conclusion, the results demonstrated that the produced formulation enhances the efficacy of EGCG under stress conditions, thus representing a potential formulation for the intracellular delivery of EGCG in diseases caused by oxidative damage
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/260787

Liposomal Formulations for an Efficient Encapsulation of Epigallocatechin-3-gallate: An in- Silico/Experimental Approach
MOLECULES
Autore/i: Laudadio, Emiliano; Minnelli, Cristina; Amici, Adolfo; Massaccesi, Luca; Mobbili, Giovanna; Galeazzi, Roberta
Classificazione: 1 Contributo su Rivista
Abstract: As a part of research project aimed to optimize antioxidant delivery, here we studied the influence of both salts and lipid matrix composition on the interaction of epigallocatechin-3-gallate (EGCG) with bilayer leaflets. Thus, we combined in silico and experimental methods to study the ability of neutral and anionic vesicles to encapsulate EGCG in the presence of Ca2+ and Mg2+ divalent salts. Experimental and in silico results show a very high correlation, thus confirming the efficiency of the developed methodology. In particular, we found out that the presence of calcium ions hinders the insertion of EGCG in the liposome bilayer in both neutral and anionic systems. On the contrary, the presence of MgCl2 improves the insertion degree of EGCG molecules respect to the liposomes without divalent salts. The best and most efficient salt concentration is that corresponding to a 5:1 molar ratio between Mg2+ and EGCG, in both neutral and anionic vesicles. Concerning the lipid matrix composition, the anionic one results in better promotion of the catechin insertion within the bilayer since experimentally we achieved 100% EGCG encapsulation in the lipid carrier in the presence of a 5:1 molar ratio of magnesium. Thus, the combination of this anionic liposomal formulation with magnesium chloride, avoids time-consuming separation steps of unentrapped active principle and appears particularly suitable for EGCG delivery applications.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/253262

Protein–protein interactions of human glyoxalase II: findings of a reliable docking protocol
ORGANIC & BIOMOLECULAR CHEMISTRY
Autore/i: Galeazzi, Roberta; Laudadio, Emiliano; Falconi, Emanuele; Massaccesi, Luca; Ercolani, Luisa; Mobbili, Giovanna; Minnelli, Cristina; Scirè, Andrea; Cianfruglia, Laura; Armeni, Tatiana
Classificazione: 1 Contributo su Rivista
Abstract: Glyoxalase II (GlxII) is an antioxidant glutathione-dependent enzyme, which catalyzes the hydrolysis of S-d-lactoylglutathione to form d-lactic acid and glutathione (GSH). The last product is the most important thiol reducing agent present in all eukaryotic cells that have mitochondria and chloroplasts. It is generally known that GSH plays a crucial role not only in the cellular redox state but also in various cellular processes. One of them is protein S-glutathionylation, a process that can occur through an oxidation reaction of proteins' thiol groups by GSH. Changes in protein S-glutathionylation have been associated with a range of human diseases such as diabetes, cardiovascular and pulmonary diseases, neurodegenerative diseases and cancer. Within a major project aimed at elucidating the role of GlxII in the mechanism of S-glutathionylation, a reliable computational protocol consisting of a protein-protein docking approach followed by atomistic Molecular Dynamics (MD) simulations was developed and it was applied to the prediction of molecular associations between human GlxII (in the presence and absence of GSH) and some proteins that are known to be S-glutathionylated in vitro, such as actin, malate dehydrogenase (MDH) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The computational results show a high propensity of GlxII to interact with actin and MDH through its active site and a high stability of the GlxII-protein systems when GSH is present. Moreover, close proximities of GSH with actin and MDH cysteine residues have been found, suggesting that GlxII could be able to perform protein S-glutathionylation by using the GSH molecule present in its catalytic site.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/259145

Selective induction of apoptosis in MCF7 cancer-cell by targeted liposomes functionalised with mannose-6-phosphate
JOURNAL OF DRUG TARGETING
Autore/i: Minnelli, Cristina; Cianfruglia, Laura; Laudadio, Emiliano; Galeazzi, Roberta; Pisani, Michela; Crucianelli, Emanuela; Bizzaro, Davide; Armeni, Tatiana; Mobbili, Giovanna
Classificazione: 1 Contributo su Rivista
Abstract: Liposomes are versatile platforms to carry anticancer drugs in targeted drug delivery; they can be surface modified by different strategies and, when coupled with targeting ligands, are able to increase cellular internalisation and organelle-specific drug delivery. An interesting strategy of antitumoral therapy could involve the use of lysosomotropic ligand-targeted liposomes loaded with molecules, which can induce lysosomal membrane permeabilization (LMP), leakage of cathepsins into the cytoplasm and subsequent apoptosis. We have previously demonstrated the ability of liposomes functionalised with a mannose-6-phosphate to reach lysosomes; in this research we compare the behaviour of M6P-modified and non-functionalised liposomes in MCF7 tumour cell and in HDF normal cells. With this aim, we first demonstrated by Western blotting the overexpression of mannose-6-phosphate/insulin-like growth factor (M6P/IGF-II) receptor in MCF7. Then, we prepared calcein-loaded liposomes and we revealed the increased uptake of M6P-functionalised liposomes in MCF7 cells respect to HDF cells by flow cytometry analysis. Finally, we loaded functionalised and not functionalised liposomes with N-hexanoyl-d-erythro-sphingosine (C6Cer), able to initiate LMP-induced apoptosis; after having studied the stability of both vesicles in the presence of serum by Dynamic Light Scattering and Spectrophotometric turbidity measurements, we showed that ceramide-loaded M6P-liposomes significantly increased apoptosis in MCF7 with respect to HDF cells. © 2017 Informa UK Limited, trading as Taylor & Francis Group
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/251684

PROTEIN-PROTEIN INTERACTION BETWEEN GLYOXALASE II AND SPECIFIC REDOX DEPENDENT PROTEINS THROUGH S-GLUTATHIONYLATION MODIFICATION
CHALLENGES IN REDOX BIOLOGY
Autore/i: Cianfruglia, Laura; Minnelli, Cristina; Andrea, Scirè; Laudadio, Emiliano; Mobbili, Giovanna; Galeazzi, Roberta; Principato, Giovanni; Armeni, Tatiana
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/260250

New lipo-nitroxides as antioxidant agents targeting lipid peroxidation.
SPIN2017_Book_of_Abstracts
Autore/i: Bortolus, Marco; Barbon, Antonio; Galeazzi, Roberta; Laudadio, Emiliano; Minnelli, Cristina; Mobbili, Giovanna; Cipolletti, Roberto; Stipa, Pierluigi
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/258268

rational design of functionalized lipids with antioxidant and scavenging activity as components of innovative artificial tears
Autore/i: Laudadio, Emiliano
Editore: Università Politecnica delle Marche
Classificazione: 8 Tesi di dottorato
Abstract: Durante i tre anni di dottorato mi sono occupato del design razionale di lipidi funzionalizzati ad attività antiossidante da utilizzare per la formulazione di lacrime artificiali. Abbiamo scelto i liposomi per veicolare le molecole antiossidanti testate; siamo partiti utilizzando l’Edaravone (EDR), il quale è stato opportunamente funzionalizzato (EDR-C18), senza diminuire le proprietà antiossidanti della molecola. Abbiamo condotto studi sperimentali evidenziando che l’EDR-C18 mantiene elevate capacità antiossidanti, solo a questo punto abbiamo condotto simulazioni di dinamica molecolare utilizzando un sistemi lipidici puri contenti fosfatidilcolina (POPC), e differenti concentrazioni di EDR-C18. I dati di simulazione hanno evidenziato una elevata stabilità dell’EDR-C18 in membrana. Abbiamo quindi determinato la concentrazione ottimale al fine di ottenere una intatta fluidità del sistema e allo stesso tempo una elevata quantità di antiossidante. Partendo da questo modello di simulazione, abbiamo creato altri sistemi di simulazione in cui abbiam investigato l’effetto dei Sali. Abbiamo testato soluzioni saline già comunemente utilizzate nella formulazione di lacrime artificiali, ed abbiamo riscontrato nel CaCl2 il sale maggiormente utile per la nostra strategia. Tali sistemi sono estremamente promettenti per la formulazione di gocce oculari. Un’altra molecola testata è l’epigallocatechin3-Gallato (EGCG). Essa ha la capacità di interagire spontaneamente con sistemi lipidici, perciò non è stata funzionalizzata. Abbiamo condotto delle simulazioni di dinamica molecolare creando sistemi lipidici misti per indagare l’effetto della matrice sulla capacità di inglobamento dell’EGCG. Abbiamo inoltre modulato la concentrazione salina ed abbiamo individuato nel sistema lipidico anionico con una quantità di Magnesio pari a 5:1 in rapporto molare con EGCG, il sistema in cui tutto l’EGCG introdotto viene inglobato, aumentando la biodisponibilità della molecola al massimo possibile.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/245340

Inhibitors of multidrug efflux pumps of Pseudomonas aeruginosa from natural sources: An in silico high-throughput virtual screening and in vitro validation
MEDICINAL CHEMISTRY RESEARCH
Autore/i: Mangiaterra, Gianmarco; Laudadio, Emiliano; Cometti, Marta; Mobbili, Giovanna; Minnelli, Cristina; Massaccesi, Luca; Citterio, Barbara; Biavasco, Francesca; Galeazzi, Roberta
Classificazione: 1 Contributo su Rivista
Abstract: Pseudomonas aeruginosa is resistant to a wide range of antibiotics, thus making troublesome the infection treatment. Efflux systems are the main mechanisms involved; among these, MexAB-OprM is a tripartite efflux pump responsible for resistance to ciprofloxacin, aztreonam, gentamicin, tetracycline and tobramycin. In an attempt to contrast antibiotic efflux, databases of natural compounds were tested for their ability to bind MexB, the inner membrane channel, using a high-throughput virtual screening approach. The comparison of their common pharmacophoric features was the basis for inhibitor identification and selection process. In silico screening against the MexB protein was performed by Autodock/Vina and further refined using a minimization/focused docking protocol on the obtained complexes. The compounds showing the best docking and resulting potentially active at nanomolar concentration have been selected and used in combination with antibiotics usually exported by MexAB-OprM in antimicrobial in vitro synergy tests (checkerboard and time kill assays) against multidrug-resistant P. aeruginosa clinical isolates. The combinations morelloflavone and pregnan-20-one-derivative/ciprofloxacin showed a four-fold MIC decrease and 100-fold increase of the bacterial killing compared to the antibiotic alone. The two chosen hits were validated by ethidium bromide accumulation assay for their efflux inhibition potency. These compounds showed the ability to increase the accumulation of ethidium bromide inside the bacterial cells as evidenced by the increase of its fluorescence in the presence of the each of them. Finally, their toxicity has been preliminary tested through hemolysis assay. The observed good correlation between in silico docking and in vitro synergy tests, indicates these two compounds as promising drugs to be used in combination therapy against MDR and MexAB-OprM overexpressing P. aeruginosa
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/245240

In vivo and in silico studies to identify mechanisms associated with Nurr1 modulation following early life exposure to permethrin in rats.
NEUROSCIENCE
Autore/i: Donatella, Fedeli; Montani, ; Laura, Bordoni; Galeazzi, Roberta; Cinzia, Nasuti; Luisa, Correia Sá; Domingues Valentina, F; Maini, Jayant; Vani, Brahmachari; Luca, Massaccesi; Laudadio, Emiliano; Rosita, Gabbianelli
Classificazione: 1 Contributo su Rivista
Abstract: The present work was designed to study the mechanisms associated with Nurr1 modulation following early life permethrin (PERM) treatment during rat's life span. Here we demonstrate that PERM exposure in rats, at a dose close to No Observed Adverse Effect Level (NOAEL) for 15days during neonatal brain development leads to its accumulation long after exposure. In striatum from adolescent rats we detected an increase in DNA methyltransferases (DNMTs) such as DNMT1, DNMT3a, Tyrosine hydroxylase, monomeric and aggregated α-synuclein protein levels. Adult rats showed enhanced DNMT3b and α-synuclein aggregation compared to the control group, while with aging a significant decrease in all biomarkers studied was observed. No changes in Nurr1 promoter methylation in adolescent, adult and old rats were found. In silico studies showed clear evidence of a strong binding interaction between PERM and its metabolite 3-phenoxybenzoic acid with the nuclear orphan receptor Nurr1. These findings suggest that an additional interference with the dopaminergic neuron pathway could occur in situ during PERM accumulation in brain. Therefore, Nurr1 modulation in early life PERM-treated rats, depends on age-related adaptive responses in animals.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/244855

Salts Influence Cathechins and Flavonoids Encapsulation in Liposomes: A Molecular Dynamics Investigation
MOLECULAR INFORMATICS
Autore/i: Laudadio, Emiliano; Mobbili, Giovanna; Minnelli, Cristina; Massaccesi, Luca; Galeazzi, Roberta
Classificazione: 1 Contributo su Rivista
Abstract: Cathechins and flavonoids are responsible of numerous health benefits. Two of the most representatives' compounds for their antioxidant and therapeutic effects are Epigallocatechin 3-Gallate (EGCG), from green tea extracts, and morelloflavone (MF), from Garcinia dulcis. Here we explore, by atomistic Molecular Dynamics simulations, how EGCG and MF interact with lipid bilayers and we show the salts' influence on their encapsulation degree in neutral liposomes. As a result, we found out that EGCGs naturally bind to the hydrophilic regions of phospholipids, positioning themselves mostly at the interface between water and lipid phases. The presence of a salt clearly influences the EGCG molecules' absorption and the total effect depends strongly on the salt nature and concentration. Beside, for MF, we observed a high stability of the intermolecular MFs aggregates in water that strongly penalizes the flavonoid's interaction with the lipid polar heads. However, salts can influence MF's liposomal penetration, even if they are not able to promote completely its absorption inside the bilayer. For both compounds, the increase of penetration is more marked in presence of magnesium chloride, whilst calcium chloride showed the opposite effect. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/251683

A molecular dynamics investigation of penetration of antioxidant lipid-based nitroxides in lipid bilayer
Conference Proceedings
Autore/i: Galeazzi, Roberta; Laudadio, Emiliano; Massaccesi, Luca; Cristina Minnelli, M.; Mobbili, Giovanna; Stipa, Pierluigi
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/249715

Liposomi funzionalizzati con mannosio-6-fosfato come Targeted Delivery Systems (TDS)”
Conference Proceedings
Autore/i: Minnelli, Cristina; Armeni, Tatiana; Cianfruglia, Laura; Crucianelli, Emanuela; Galeazzi, Roberta; Laudadio, Emiliano; Mobbili, Giovanna; Pisani, Michela; Stipa, Pierluigi
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/249735

Virtual screening of efflux pump inhibitors and in vitro activity against multidrug- resistant Pseudomonas aeruginosa.
International Conference of Antimicrobial Research (ICAR).
Autore/i: Mangiaterra, G.; Laudadio, E.; Mobbili, G.; Biavasco, F.; Minnelli, C.; Galeazzi, R.
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/263524

A combined EPR-molecular dynamics investigation of penetration of antioxidant lipid-based nitroxides in lipid bi-layer
Conference Proceedings
Autore/i: Laudadio, Emiliano; Galeazzi, Roberta; Minnelli, Cristina; Mobbili, Giovanna; Stipa, Pierluigi
Classificazione: 4 Contributo in Atti di Convegno (Proceeding)
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/249710

Recent advances in Computational Simulations of Lipid Bilayer Based Molecular Systems
Frontiers in Computational Chemistry Vol. 2
Autore/i: Galeazzi, Roberta; Laudadio, Emiliano; Massaccesi, Luca
Editore: Bentham Science Publishers
Classificazione: 2 Contributo in Volume
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/222718

Permethrin and its metabolites affects Cu/Zn Superoxide conformation: fluorescence and in silico evidences
MOLECULAR BIOSYSTEMS
Autore/i: R., Gabbianelli; M., Carloni; F., Marmocchi; C., Nasuti; D., Fedeli; Laudadio, Emiliano; Massaccesi, Luca; Galeazzi, Roberta
Classificazione: 1 Contributo su Rivista
Abstract: The proclivity of permethrin and its metabolites to affect the structure and activity of Cu/Zn superoxide dismutase (SOD) has been investigated by using intrinsic fluorescence and 8-ANS fluorescence techniques. In silico molecular docking investigations were carried out in order to assess the means of interaction at a molecular level between SOD and the considered ligands. Results show that both, permethrin and its metabolites are able to induce conformational variation on SOD. Permethrin and 3-phenoxybenzyl alcohol metabolite induce a blue shift toward the hydrophobic amino acids Leu-101, Ile-102, Leu-104, Ile-110 and Ile-111, with a significant peak increase. An opposite effect was shown by 3-phenoxy benzaldehyde and 3-phenoxybenzoic acid with a progressive reduction of tyrosine fluorescence emission, without any shift. Computational findings confirm that all the molecules considered have more than one allosteric binding site but none of them interact with SOD at its catalytic Cu/Zn cleft. Moreover, all the binding poses found are very close in binding energy thus demonstrating that there is not only a preferred interaction site but most of them are important due to their relative energy in equilibrium with a population strictly connected to the ligand concentration. In the obtained complexes, all the ligands are involved in many hydrogen bonds through their polar oxygen moieties but due to the presence of a common aromatic hydrophobic core, many hydrophobic interactions are due to the SOD nature rich in apolar amino acids. Furthermore, for each ligand it can be pointed out the presence of a highly populated docked structure with a specific interaction of permethrin and its metabolites with Tyr-108, responsible for changes in fluorescence emission.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/222717

Liposome-based gene delivery systems containing a steroid derivative: computational and small angle X-ray diffraction study
RSC ADVANCES
Autore/i: Galeazzi, Roberta; Bruni, Paolo; Crucianelli, Emanuela; Laudadio, Emiliano; Marini, Milvia; Massaccesi, Luca; Mobbili, Giovanna; Pisani, Michela
Classificazione: 1 Contributo su Rivista
Abstract: In this study, the structural properties and the phase behaviour of mixed composition neutral liposomes containing a functionalized steroid are reported. With the aim to design neutral liposomes able to coordinate cations and to complex DNA, we synthesized cholesteryl-2-(picolinamido)-phenylcarbamate (CHOLp) containing an N-aryl picolinamide group as chelating agent linked to the steroid structure via a carbamate moiety. The phase behaviour of mixtures of the functionalized cholesterol (CHOLp) and dioleoyl-phosphatidylcholine (DOPC) was investigated by means of X-ray diffraction. Simultaneously, atomistic molecular dynamics simulations of DOPC/CHOLp bilayers as a function of CHOLp molar fractions were carried out to investigate the specific effects of the polar steroid on the structural and dynamic properties of these zwitterionic bilayers. The molecular modelling studies have been performed both in absence and in presence of bivalent cations salts in order to assess the CHOLp ability to coordinate metal ions. The results show good stability of the resulting DOPC/CHOLp bilayers which is improved by the presence of salt. This is particularly evident at low amount of CHOLp where a high order of the lipid tails can be observed, suggesting stabilization of the corresponding DOPC liposomes. This feature can be ascribed to the polar nature and structural properties of the ligand. In fact, due to the presence of the aromatic moieties, CHOLp combines two different behaviours, namely a propensity to realize both intermolecular π-stacking interactions and cation–π bonding mainly evident in CaCl2. The last feature confirms for CHOLp a role as a cation-mediated complexation agent for DNA. The X-ray diffraction data on the capability of DOPC/CHOLp liposomes to complex DNA was also reported.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/228347

Insights into the Influence of 5-HT2c aminoacidic variants with the inhibitory action of Serotonin inverse agonists and antagonists
JOURNAL OF MOLECULAR MODELING
Autore/i: Galeazzi, Roberta; Massaccesi, L.; Piva, Francesco; Principato, Giovanni; Laudadio, E.
Classificazione: 1 Contributo su Rivista
Abstract: Specific modulation of serotonin 5-HT(2C) G protein-coupled receptors may be therapeutic for obesity and neuropsychiatric disorders. The different efficacy of drugs targeting these receptors are due to the presence of genetic variants in population and this variability is still hard to predict. Therefore, in order to administer the more suitable drug, taking into account patient genotype, it is necessary to know the molecular effects of its gene nucleotide variations. In this work, starting from an accurate 3D model of 5-HT(2C), we focus on the prediction of the possible effect of some single nucleotide polymorphisms (SNPs) producing amino acidic changes in proximity of the 5-HT(2C) ligand binding site. Particularly we chose a set of 5-HT(2C) inverse agonists and antagonists which have high inhibitory activity. After prediction of the structures of the receptor-ligand complexes using molecular docking tools, we performed full atom molecular dynamics simulations in explicit lipid bilayer monitoring the interactions between ligands and trans-membrane helices of the receptor, trying to infer relations with their biological activity. Serotonin, as the natural ligand was chosen as reference compound to advance a hypothesis able to explain the receptor inhibition mechanism. Indeed we observed a different behavior between the antagonists and inverse agonist with respect to serotonin or unbounded receptor, which could be responsible, even if not directly, of receptor's inactivation. Furthermore, we analyzed five aminoacidic variants of 5HT(2C) receptor observing alterations in the interactions between ligands and receptor which give rise to changes of free energy values for every complex considered.
Scheda della pubblicazione: https://iris.univpm.it/handle/11566/151708