Maurizio Fermeglia

• Professor (Full) at University of Trieste

Hydrogen is a versatile energy carrier and storage medium that may be employed in a variety of applications. According to the industrial processes used for its production, hydrogen may be labelled using different colours: (i) grey hydrogen, produced from natural gas using steam methane reforming (SMR), (ii) blue hydrogen, like the grey one, but wit...

Hydrogen is a versatile energy carrier and storage medium that is expected to have a key role in the energy transition, as it can be employed in a variety of applications. Hydrogen can be produced from different feedstocks and using different processes. Based on the production technology used, hydrogen is conventionally identified by a color. In th...

The iron and steel sector is one of the dominant drivers behind economic and social progress, but it is also very energy-intensive and hard-to-abate, making it a major cause of global warming. Improving energy efficiency, introducing hydrogen for direct reduction, and utilising CCS technologies are the three most viable options for reducing CO2 emi...

In June 1972, Giorgio Soave published a renown scientific paper (Equilibrium constants from a modified Redlich-Kwong equation of state, Chemical Engineering Science, 27, 1197-1203), which is one of the most ever cited papers in the field of Chemical Engineering. In the 50th anniversary of this publication it seems appropriate to give a tribute to t...

Most of the actual industrial research efforts are aimed at reducing environmental burdens associated with human activities in the context of sustainable development. This trend has become increasingly prevalent in the naval transportation sector shown by a growing number of scientific publications dealing with life cycle assessments of maritime-re...

Most of the actual industrial research efforts are aimed at reducing environmental burdens associated with human activities in the context of sustainable development. This trend has become increasingly prevalent in the naval transportation sector shown by a growing number of scientific publications dealing with life cycle assessments of maritime-re...

This paper aims at broadening the perspective in life cycle assessment methodology, exploiting multiscale modelling towards the generation of life cycle inventory data during an early-stage product design. Our approach involves the usage of molecular modelling techniques, such as electronic, atomistic or mesoscale models, in combination with contin...

In view of the low-carbon transformation of the power sector, natural gas-fired power generation is the only technology, among fossil resources, that will continue to provide an important source of flexibility for the power system in the coming years. However, the carbon dioxide emissions produced by the operation of such plants call for carbon cap...

The breast cancer type 1 susceptibility protein (BRCA1) and its partner – the BRCA1-associated RING domain protein 1 (BARD1) – are key players in a plethora of fundamental biological functions including, among others, DNA repair, replication fork protection, cell cycle progression, telomere maintenance, chromatin remodeling, apoptosis and tumor sup...

One of the major challenges of Life Cycle Assessment is in the generation of life cycle inventories for complex or novel materials. This paper aims at broadening the perspective in Life Cycle Assessment methodology, exploiting multiscale modelling towards the generation of inventory data during an early-stage product design. Our approach involves t...

The steel industry is currently a major water pollution source, releasing high quantities of chemicals. One of the pollutants is phenol, known for its toxicity even when it is present in low concentrations. Liquid-liquid extraction employing various aromatics and cycloalkanes (i.e., benzene, toluene, cyclohexane, ethylbenzene) and ketones (i.e., me...

Nowadays, computer simulations have been established as a fundamental tool in the design and development of new dendrimer-based nanocarriers for drug and gene delivery. Moreover, the level of detail contained in the information that can be gathered by performing atomistic-scale simulations cannot be obtained with any other available experimental te...

siRNAs are emerging as promising therapeutic agents due to their ability to inhibit specific genes in many diseases. However, these tools require specific vehicles in order to be safely delivered to the targeted site. Among different siRNA delivery systems, self-assembled nanomicelles based on amphiphilic cationic dendrons (ACDs) have recently outp...

This chapter reviews the different techniques for analyzing the chemical-physical properties, transfection efficiency, cytotoxicity, and stability of covalent cationic dendrimers (CCDs) and self-assembled cationic dendrons (ACDs) for siRNA delivery in the presence and absence of their nucleic cargos. On the basis of the reported examples, a standar...

One of the major goals of computational materials science is the rapid and accurate prediction of properties of new materials.

Energy, water, and food shortages, along with irreversible environmental damage and climate changes, are bound to happen within a decade if the current course of action is maintained, preparing the “perfect storm”–a chain of interrelated events that could lead to major stress on the global system.Energy plays a central role in the complex balance b...

The recent emergence of the pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent for the coronavirus disease-2019 (COVID-19), is causing a global pandemic that poses enormous challenges to global public health and economy. SARS-CoV-2 host cell entry is mediated by the interaction of the viral transmembrane sp...

Biology is dominated by polyanions (cell membranes, nucleic acids, and polysaccharides just to name a few), and achieving selective recognition between biological polyanions and synthetic systems currently constitutes a major challenge in many biomedical applications, nanovectors-assisted gene delivery being a prime example. This review work summar...

The maintenance of genome integrity is essential for any organism survival and for the inheritance of traits to offspring. To the purpose, cells have developed a complex DNA repair system to defend the genetic information against both endogenous and exogenous sources of damage. Accordingly, multiple repair pathways can be aroused from the diverse f...

In this chapter, we will review the nanomedicines which are already available on the market, those that are currently in clinical trials, and the nanoformulations at the preclinical/translational stage for the treatment of breast cancer. The major drawbacks hampering the pathway of breast cancer nanomedicines to the clinics will be also presented a...

The fast development of digitalization and computational science is opening new possibilities for a rapid design of new materials. Computational tools coupled with focused experiments can be successfully used for the design of new nanostructured materials in different sectors, particularly in the area of biomedical applications. This paper starts w...

This review work reports a collection of coupled experimental/computational results taken from our own experience in the field of self-assembled dendrimers for heparin binding. These studies present and discuss both the potentiality played by this hybrid methodology to the design, synthesis, and development of possible protamine replacers for hepar...

Small interfering RNAs (siRNAs) represent a new approach towards the inhibition of gene expression; as such, they have rapidly emerged as promising therapeutics for a plethora of important human pathologies including cancer, cardiovascular diseases, and other disorders of a genetic etiology. However, the clinical translation of RNA interference (RN...

In part I of this review, the authors showed how poly(amidoamine) (PAMAM)-based dendrimers can be considered as promising delivering platforms for siRNA therapeutics. This is by virtue of their precise and unique multivalent molecular architecture, characterized by uniform branching units and a plethora of surface groups amenable to effective siRNA...

Human Respiratory Syncytial Virus (RSV) is the primary cause of bronchopneumonia in infants and children worldwide. Clinical studies have shown that early treatments of RSV patients with ribavirin improve prognosis, even if the use of this drug is limited due to myelosuppression and toxicity effects. Furthermore, effective vaccines to prevent RSV i...

A number of new F-triazolequinolones (FTQs) and alkoxy-triazolequinolones (ATQs) were designed, synthesized and evaluated for their activity against Mycobacterium tuberculosis H37Rv. Five out of 21 compounds exhibited interesting minimum inhibitory concentration (MIC) values (6.6–57.9 μM), ATQs generally being more potent than FTQs. Two ATQs, 21a a...

Gastrointestinal stromal tumors are mesenchymal tumors arising in the stomach and small bowel and more rarely in the rectum, esophagus, peritoneum and retroperitoneum. These tumors are characterized by KIT or PDGFRA mutations. KIT mutations are all in frame and lead to constitutive tyrosine kinase domain activation without ligand binding. Mutations...

[This corrects the article DOI: 10.18632/oncotarget.20469.].

In this work, we propose a framework for the preliminary screening of chemical process designs according to sustainability criteria. Implementing each flowsheet in a process simulator, several indicators based on sustainability pillars, i.e. economy, society and environment, are calculated and then analyzed employing data envelopment analysis (DEA)...

The need for effective and efficient design and production of sophisticated materials with advanced performances on a competitive time scale is strongly driving the integration of material modeling and simulation techniques into material selection decision processes. Specifically, for complex structural materials such as polymer-based nanocomposite...

Bovine viral diarrhea virus (BVDV) infection is still a plague that causes important livestock pandemics. Despite the availability of vaccines against BVDV, and the implementation of massive eradication or control programs, this virus still constitutes a serious agronomic burden. Therefore, the alternative approach to combat Pestivirus infections,...

A current challenge of physical, chemical, and engineering sciences is to develop computational tools for predicting the structure and properties of complex materials from the knowledge of a few input parameters. Accordingly, in this chapter, we present a multiscale molecular simulation protocol for predicting morphologies and properties of nanostr...

This work presents a multi-scale approach to reacting and expanding polyurethane (PU) foams modeling and simulation. The modeling strategy relies on two pillars: an atomistic model (molecular dynamics (MD)/Grand Canonical Monte Carlo (GCMC)) that provides liquid mixture density and reactant solubility and a continuum model (CFD) in which the expans...

Enteroviruses are among the most common and important human pathogens for which there are no specific antiviral agents approved by the US Food and Drug Administration so far. Particularly, coxsackievirus infections have a worldwide distribution and can cause many important diseases. We here report the synthesis of new 14 quinoxaline derivatives and...

Heparin is a sulfated glycan widely used as anticoagulant in medicine. Mallard Blue (MalB), a small cationic dye developed in our laboratories, is able to detect heparin in serum and plasma in a dose-response manner, with performance superior to its direct competitors. However, many aspects of MalB/heparin binding still remain to be explored which,...

Data S1. Computational details.

Table S1. Binding free energies (ΔGbind) and binding free energy differences (ΔΔGbind) for the WT, T41A and S45F β‐catenin in complex with α‐catenin.

Table S2. List of the 382 genes differentially expressed between mutated‐ and wt‐DT patients.

In this paper we report the synthesis, in vitro anticancer activity, and the experimental/computational characterization of mechanism of action of a new series of E isomers of triazolo[4,5-b/c]pyridin-acrylonitrile derivatives (6c-g, 7d-e, 8d-e, 9c-f, 10d-e, 11d-e). All new compounds are endowed with moderate to interesting antiproliferative activi...

45° Congresso naxionale della società italiana di microbiologia

Quinoxaline derivatives as new leads against Picornavirus.

The actual strategy to improve current therapies in advanced prostate cancer involves targeting genes activated by androgen withdrawal, either to delay or prevent the emergence of the castration-refractory phenotype. However, these genes are often implicated in several physiological processes, and long-term inhibition of survival proteins might be...

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. GISTs express the receptor tyrosine kinase KIT, and the majority of GISTs present KIT gain-of-function mutations that cluster in the 5' end of the receptor juxtamembrane domain. On the other hand, little information is known about GISTs car...

This chapter presents the three-dimensional (3D) model of the Sigma1 receptor protein as obtained from homology modeling techniques. We show the applicability of this structure to docking-based virtual screening and discuss combined in silico/in vitro mutagenesis studies performed to validate the structural features of the Sigma1 receptor model and...

The present contribution integrates structural, computational, and molecular biology techniques to understand the eventual role of our newly reported hot-spot mutations of the BCR-ABL1 KD in TKI resistance observed in CML patients (1) using a "two-tier level" investigation: isolated KDs and SH2-liker-SH3-KD BCR-ABL1 constructs. Specifically, in sil...

Desmoid- type fibromatosis (DF) is a rare mesenchymal lesion with high risk of local recurrence. Specific β-catenin mutations (S45F) appeared to be related to this higher risk compared to T41A mutated or wild type (WT). We explored the influence of both mutations and WT on structure stability and affinity of β-catenin for α-catenin and the pattern...

The influence of morphology and cell gas composition on heat insulation properties of polyurethane (PU) foams was investigated using a multi-scale mathematical model. The polymer absorption coefficient was determined from quantum chemical computations. Reverse non-equilibrium molecular dynamics was used to calculate the thermal conductivity of poly...

Spirocyclic thiophene derivatives represent promising sigma-1 ligands with high sigma-1 affinity and selectivity over the sigma-2 subtype. In order to increase ligand efficiency, the thiophene ring was replaced bioisosterically by a thiazole ring and the pyran ring was opened. Late-stage diversification by regioselective C-H arylation of thiazoles...

Supramolecular dendrimers created from small amphiphilic dendrons are able to mimic covalently constructed high‐generation dendrimers for siRNA delivery, as presented by S. Pricl, L. Peng, and co‐workers on page 3667. An optimal balance between the hydrophobic alkyl chain length and the hydrophilic dendritic portion is crucial for self‐assembly of...

In this work we applied a blend of computational and synthetic techniques with the aim to design, synthesize, and characterize new σ1 receptor (σ1R) ligands. Starting from the structure of previously reported, high-affinity benzoxazolone-based σ1 ligands, the three-dimensional homology model of the σ1R was exploited for retrieving the molecular det...

Self‐assembly is a fundamental concept and a powerful approach in molecular science. However, creating functional materials with the desired properties through self‐assembly remains challenging. In this work, through a combination of experimental and computational approaches, the self‐assembly of small amphiphilic dendrons into nanosized supramolec...

A set of stereoisomeric 2,5-diazabicyclo[2.2.2]octanes 14 and 15 was prepared in a chiral-pool synthesis starting from (S)- or (R)-aspartate. The key step in the synthesis was a Dieckmann-analogous cyclization of (dioxopiperazinyl)acetates 8, which involved trapping uf the intermediate hemiketal anion with Me3SiCl. The σ1 affinity was tested using...

Supporting Information

Acrylic acid, one of the most important monomers, has a wide range of uses e.g. in the paints adhesives, textile finishing, leather processing or super absorbents. The production process from propylene is well known and used at industrial scale in the USA, Europe, and Asia. The present paper focuses on the evaluation of the environmental impact of...

In this work, we present and discuss a comprehensive set of both newly and previously synthesized compounds belonging to 5 distinct molecular classes of linear aromatic N-polycyclic systems that efficiently inhibits bovine viral diarrhea virus (BVDV) infection. A coupled in silico/in vitro investigation was employed to formulate a molecular rationa...

We present a combined theoretical/experimental study to investigate the effect of selective solvent vapor annealing treatment on the obtainment of highly ordered morphologies of symmetric poly(styrene-b-methyl methacrylate) diblock copolymer (PS-b-PMMA DBC) films loaded with compatibilized magnetic (Fe3O4) nanoparticles (NPs). Different amounts of...

In this work, the structural features of spherical gold nanoparticles (NPs) decorated with highly-grafted poly(styrene) (PS), poly(vinylpyridine) (PVP) and PS-PVP diblock copolymer brushes immersed in a good solvent are investigated by of means Dissipative Particle Dynamics (DPD) simulations as a function of grafted chain length and of homopolymer...

Low-generation viologen-phosphorous dendrimers (VPDs) can be exploited as novel therapeutic agents, since they efficiently inhibit aggregation of amyloid-β into fibrils and are active against several strains of microorganisms. Human serum albumin (HSA), the most abundant plasma protein, is playing an increasing role as drug carrier in the clinical...

Here, we report for the first time on a facile method for the preparation of novel drug delivery systems based on supramolecular interactions between β-cyclodextrin-polyglycerol conjugates (β-CD-g-PG) and human serum albumin (HSA). The results obtained by combined experimental/modeling studies showed that the main drivers to the formation of HSA/β-...

In this work we describe and assess the performance of Nanotools, a feature of the MoDena software we are currently developing in the framework of a granted EU project devoted to the implementation of a multiscale modeling environment for nanomaterials and systems by design. Specifically, Nanotools integrates multi-step computational procedures bas...

Background Our recent work revealed that some chronic myeloid leukemia (CML) patients failing imatinib therapy carry the BCR-ABL1 V304D mutation, and is associated with poor clinical outcomes. BCR-ABL1 V304D variant has rarely been described in clinical specimens, and its location within the BCR-ABL1 Kinase Domain (KD) appears to be in an area of t...

Linear aromatic N-tricyclic compounds with promising antiviral activity and minimal cytotoxicity were prepared and analyzed in the last years. Specifically, the pyrido[2,3-g]quinoxalinone nucleus was found endowed with high potency against several pathogenic RNA viruses as etiological agents of important veterinary and human pathologies. Following...

Transport and surface interactions of proteins in nanopore membranes play a key role in many processes of biomedical importance. Although the use of porous materials provides a large surface-to-volume ratio, the efficiency of the operations is often determined by transport behavior, and this is complicated by the fact that transport paths (i.e., th...

STAT3 is a key element in many oncogenic pathways and, like other transcription factors, is an attractive target for development of novel anticancer drugs. However, interfering with STAT3 functions has been a difficult task and very few small molecule inhibitors have made their way to the clinic. OPB-31121, an anticancer compound currently in clini...

Significance Nanotechnology-based drug delivery is expected to bring new hope for cancer treatment by enhancing anticancer drug efficacy, overcoming drug resistance, and reducing drug toxicity. In this respect, we developed an innovative drug delivery system based on a self-assembling amphiphilic dendrimer, which can generate supramolecular nanomic...

We report the design, synthesis and binding evaluation against σ1 and σ2 receptors of a series of new piperidine-4-carboxamide derivatives variously substituted on the amide nitrogen atom. Specifically, we assessed the effects exerted on σ receptor affinity by substituting the N-benzylcarboxamide group present on a series of compounds previously sy...

siRNA delivery remains a major challenge in RNAi-based therapy. Here, we report for the first time that an amphiphilic dendrimer is able to self-assemble into adaptive supramolecular assemblies upon interaction with siRNA, and effectively delivers siRNAs to various cell lines, including human primary and stem cells, thereby outperforming the curren...

Basal cell carcinomas (BCCs) and a subset of medulloblastomas are characterized by loss‐of‐function mutations in the tumor suppressor gene, PTCH1. PTCH1 normally functions by repressing the activity of the Smoothened (SMO) receptor. Inactivating PTCH1 mutations result in constitutive Hedgehog pathway activity through uncontrolled SMO signaling. Tar...

Generation 2 cationic carbosilane dendrimers hold great promise as internalizing agents for gene therapy as they present low toxicity, retain and internalize genetic material as oligonucleotide or siRNA. In this work we carried out a complete in silico structural and energetical characterization of the interactions of a set of 2G carbosilane dendri...

In our recent researches racemic RC-33 was identified as a potent and highly promising σ1 receptor agonist, showing excellent σ1 receptor affinity and promoting the NGF-induced neurite outgrowth in PC12 cell at very low concentrations. Surprisingly, its interaction with the biological target as well as its effect on neurite sprouting were proved to...

siRNA delivery remains a major challenge in RNAi-based therapy. Here, we report for the first time that an amphiphilic dendrimer is able to self-assemble into adaptive supramolecular assemblies upon interaction with siRNA, and effectively delivers siRNAs to various cell lines, including human primary and stem cells, thereby outperforming the curren...

This study investigates transgeden (TGD) dendrimers (polyamidoamine (PAMAM)-type dendrimers modified with rigid polyphenylenevinylene (PPV) cores) and compares their heparin-binding ability with commercially available PAMAM dendrimers. Although the peripheral ligands are near-identical between the two dendrimer families, their heparin binding is ve...

Modelling and simulation of sol–gel nanocomposites is a promising method for understanding the properties at molecular level and consequently improving and quickening the design of such materials. In the present chapter, a hierarchical procedure for bridging the gap between atomistic and macroscopic modelling via mesoscopic simulations will be pres...

2-Oxoglutaric acid (2-OG) has gained considerable attention because of its newly discovered signalling role in addition to its established metabolic functions. With the aim of further exploring the signalling function of 2-OG, here we present a structure-activity relationship study using 2-OG probes bearing different carbon chain lengths and termin...

The σ1 receptor is an integral membrane protein that shares no homology with other receptor systems, has no unequivocally identified natural ligands, but appears to play critical roles in a wide variety of cell functions. While the number of reports of the possible functions of the σ1 receptor is increasing, almost no information about the three-di...

Significance Mutations within the BCR-ABL1 kinase domain lead to resistance to tyrosine kinase inhibitor (TKI) therapy in chronic myeloid leukemia. We show a high prevalence of compound BCR-ABL1 mutations (polymutants) in patients failing TKIs. Molecular dynamics analyses of the most frequent polymutants in complex with TKIs unveiled the basis of T...

The inappropriate activation of Hedgehog (Hh) pathway is involved in the pathogenesis of skin basal cell carcinoma (BCC). Loss of function of the transmembrane receptor Patched (PTCH1), or gain of function of the Smoothened (SMO), Sonic Hh (SHH), and GLI family transcription factors can be ligand-independent oncogenic drivers of this disease. The a...

The acquisition of mutations within the BCR-ABL1 kinase domain is frequently associated to imatinib failure among patients with chronic myeloid leukemia (CML). Typically, patients failing imatinib undergo sequential therapy with second line tyrosine kinase inhibitors (TKIs) such as nilotinib or dasatinib. To investigate the prevalence of BCR-ABL1 m...

This article reports self-assembling dendrons which bind DNA in a multivalent manner. The molecular design directly impacts on self-assembly which subsequently controls the way these multivalent nanostructures bind DNA - this can be simulated by multiscale modelling. Incorporation of an S-S linkage between the multivalent hydrophilic dendron and th...

The structure of copper(ii) complexes formed with triethanolamine (TEA) core poly(amidoamine) (PAMAM) dendrimers from generation 0 (G0) to 4 (G4) were investigated by the electron paramagnetic resonance (EPR) technique and molecular simulations. Different square planar coordination modes were detected as a function of copper(ii) concentration, whos...

BACKGROUND Ponatinib targets the inactive conformation of the ABL1 kinase and avoids interacting with the side chain of the mutated 315 residue. In vitro, ponatinib inhibits all single-point BCR-ABL1 mutations. Yet, a significant proportion of patients with chronic myeloid leukemia in chronic phase (CML–CP) do not respond to ponatinib and a subset...

A 2-oxoglutaric acid (2-OG) probe bearing a methylene group introduced at the C4 position and a vinyl group to replace the carbonyl group at the C2 position elicited characteristic affinity for NtcA, the 2-OG receptor, while maintaining the signaling function of the parent natural metabolite 2-OG. This discovery opens new perspectives in the design...

A current challenge of physical, chemical, and engineering sciences is to develop theoretical tools for predicting structure and properties of complex materials from the knowledge of a few input parameters. In this work, we present a general multiscale molecular simulation protocol for predicting morphologies and properties of nanostructured polyme...

Small interfering RNAs (siRNAs) have attracted considerable attention as compelling therapeutics providing safe and competent delivery systems are available. Dendrimers are emerging as appealing siRNA delivery vectors thanks to their unique, well-defined architecture and the resulting cooperativity and multivalency confined within a nanostructure....

Our recent research efforts identified racemic RC-33 as a potent and metabolically stable σ1 receptor agonist. Herein we describe the isolation of pure RC-33 enantiomers by chiral chromatography, assignment of their absolute configuration, and in vitro biological studies in order to address the role of chirality in the biological activity of these...

Dasatinib is a second-generation BCR-ABL inhibitor approved for the treatment of patients with chronic myeloid leukemia, both in the frontline and in the imatinib-resistant/intolerant settings. The high affinity of dasatinib for the protein is currently assumed to result from its ability to bind both the active and inactive conformations of the BCR...

Dendrimers are important molecules that are currently undergoing investigation for use in a variety of different biomedical applications. This book explores the use of dendrimers for a variety of potential functions, including antiamyloidogenic agents, drug delivery systems, nucleic acid and RNA delivery vectors and to produce hybrid fibre platform...