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Innovative and sustainable solar cells based on abundant elements on the earth's crust
No full textCurrently, thin-film technology facilitates the production of high-efficiency solar cells at costs that are competitive with traditional Silicon technology. However, the development of these devices has largely overlooked the abundance of constituent elements found in the Earth's crust. For instance, Indium, Gallium, and Tellurium, are considered rare elements, as noted by the European Community. To address this concern, researchers are investigating new compounds made of abundant elements, aiming to create solar cells that are sustainable in the long term. The literature features studies on many innovative materials including WSe3, Cu2ZnSnSe4, SnSe2, Sb2Se3, and FeS2, which are being explored as absorber layers in thin-film solar cells.
In particular, antimony selenide (Sb2Se3) is emerging as one of the most promising candidate materials for use as an absorber for thin-film solar cells, thanks to its non-toxic nature and the abundance of its constituent elements in the Earth's crust. Sb2Se3 exhibits exceptional properties, including an optimal energy gap that theoretically allows a maximum efficiency of 33%, alongside a high absorption coefficient in the visible spectrum. In recent years, significant advancements have been made, leading to a maximum photovoltaic conversion efficiency (PCE) exceeding 10%. However, this is still considerably below its theoretical limit. The limitations in PCE can be attributed to several factors, particularly the high degree of anisotropy exhibited by this material. Key challenges include the difficulty in controlling the growth of Sb2Se3 grains along the crystallographic direction necessary for optimal charge transport, the interaction and band-offset with different n-type partners depending on whether the cell architecture is substrate- or superstrate-based, and the challenge of achieving a back-contact that fulfills the requirements for ohmicity.
In this PhD thesis, an effort was made to the primary limiting factors affecting the ability to surpass the photovoltaic efficiency record by examining Sb2Se3-based solar cells configured in a superstrate arrangement.
From a crystallographic perspective, the structural characterization of Sb2Se3 films revealed that their crystalline quality and preferred orientation are significantly influenced by the choice of window layer, which act as substrate for the Sb2Se3 growth. To gain a deeper understanding of the growth mechanism, Sb2Se3 thin films were deposited via close-spaced sublimation (CSS) onto five different window layers: CdS, CdS:F, CdSe, As2S3, and ZnCdS. Solar cells based on Sb2Se3, fabricated in a superstrate configuration using these various substrates, clearly demonstrate the impact of the preferential orientation of Sb2Se3 on photovoltaic performance.
The synthesis of antimony selenide can be accomplished using various low-cost techniques that are easily scalable for industrial applications, such as Chemical Bath Deposition, Close-Spaced Sublimation, Vapor Transport Deposition, Rapid Thermal Evaporation, Ion Vapor Deposition, and Radio-Frequency Magnetron Sputtering. This versatility is largely attributed to the absence of polymorphism and a relatively low melting point (885 K). However, once the substrate is established, the growth of Sb2Se3 is significantly influenced by its propensity to form defects and stoichiometric deviations. This thesis includes an in-depth study on the CSS growth of Sb2Se3. In particular, it has been demonstrated how the Ar counterpressure introduced into the growth chamber has a substantial impact on the material's stoichiometry and preferred growth orientation.
Another critical factor in surpassing the 10% PCE threshold is the exploration of various materials to achieve an ohmic contact with low resistivity, for use as a back contact. This thesis proposes an innovative compound based on Fe, S, and O elements. Given the extreme abundance of these elements in the Earth's crust and their non-toxicity nature, the synthesis technique used is also straightforward. Specifically, the Fe-S-O thin film is deposited at room temperature using radio-frequency magnetron sputtering. XRD and Raman analyses revealed that the material is composed of two phases: Fe3O4 in both orthorhombic and cubic forms, and FeS in the troilite phase. This material establishes an effective ohmic contact on the antimony selenide thin film, yielding a contact resistivity of 0.8 Ω⋅cm², as determined from the current-voltage characteristics of fully assembled Sb2Se3-based solar cells. After three months of monitoring the photovoltaic parameters, a negligible average variation was observed. Another important factor, related to the CBO between the n-type window material and antimony selenide, is the phenomenon known as the Voc deficit. Indeed, literature reports indicate that solar cell consistently exhibit an open-circuit voltage significantly lower than the theoretical. In this thesis, a comprehensive analysis of an Sb2Se3 solar cell in the typical superstrate configuration was conducted. By investigating of current density-voltage characteristics as functions of temperature and wavelength, along with capacitance-voltage measurements and admittance spectroscopy, we attribute the observed low open-circuit voltage to the presence of a potential barrier within the absorber material particularly near the junction interface.
In conclusion, this thesis presents a comprehensive investigation into the realization and performance optimization of Sb2Se3-based solar cells. Emphasizing low-cost and scalable techniques such as Close-Spaced Sublimation and sputtering, we explore the influence of growth conditions, including argon counterpressure, on material stoichiometry and preferred crystallographic orientation. The development of an innovative Fe-S-O compound as a back contact material demonstrates significant promise, achieving an ohmic contact with low resistivity and maintaining stable photovoltaic parameters over time. Furthermore, our analysis reveals the critical role of the conduction band offset and the associated Voc deficit in limiting the open-circuit voltage of Sb2Se3 solar cells. By elucidating the underlying mechanisms affecting device performance, this work contributes valuable insights toward enhancing the efficiency of Sb2Se3-based solar technologies, paving the way for future advancements in the field
Supramolecular fluorescent probes for investigating dynamic processes at the molecular level
No full textThis thesis aims to explore the use of novel fluorescent probes for monitoring three distinct dynamic processes in biological systems and synthetic materials: cell contraction, protein aggregation, and polymer elongation. A range of fluorogenic compounds, from small molecules to more complex calixarene-based bichromophoric systems, have been designed, synthesized and studied, each tailored to probe these processes through innovative sensing mechanisms.
The thesis is organized in four chapters.
After a first introductory chapter on the use of linear and nonlinear fluorescence techniques for optical sensing, the second chapter is devoted to the development of fluorescent probes designed to image the contraction mechanism in cardiac cells using nonlinear optical methods. Two distinct approaches are explored, both based on the incorporation of the probes within the cell membrane. The first strategy uses small fluorescent quadrupolar dyes capable of responding to the electrical changes occurring during cell contraction through electrochromism and second harmonic generation. The second approach involves calixarene-based bichromophoric systems designed to undergo conformational changes in response to myocardial contraction, triggering an optical response. This last approach is based on the hypothesis that the lateral mechanical forces, generated within the cell membrane, could alter the conformation of the scaffold, thereby modulating the intramolecular interactions between the dyes, and inducing a change in the spectroscopic properties of the probe. In addition to the synthesis and the spectroscopic characterization of the dyes, the chapter reports the preliminary results obtained from experiments where cardiomyocytes were incubated with the dyes and analysed using multiphoton microscopy, in collaboration with Prof. Michele Miragoli and Prof. Francesca Terenziani at the Dipartimento di Medicina e Chirurgia and Dipartimento di Scienze Chimiche, della Vita e della Sostenibilità Ambientale, respectively, of the University of Parma.
The third chapter focuses on the design and synthesis of calixarene-based mechanophores for the development of mechanoresponsive luminescent polymeric materials. This research was partially conducted at the Institut Català d'Investigació Química (ICIQ) in Tarragona (ES), under the supervision of Dr. José Augusto Berrocal. The chapter details the synthesis of calix[4]arenes derivatives functionalized with two pyrene units and investigates the intramolecular dimerization between the two chromophores, a process facilitated by the flexibility of the macrocyclic structure. Subsequently, the calixarene-based systems were covalently incorporated into polymeric matrices to confer mechanoresponsive properties. It was demonstrated that the application of mechanical tensile forces to the polymer films could physically dissociate the pyrene dimer, resulting in a measurable change in the fluorescence properties of the material.
The fourth chapter aims to study the dynamics of protein aggregation using two-dimensional electronic spectroscopy. This technique exploits nonlinear spectroscopy to achieve an ultrafast temporal resolution, allowing the investigation of rapid molecular events. The method relies on labelling the aggregating proteins with fluorescent probes capable of undergoing energy transfer processes. Indeed, by monitoring variations in energy transfer efficiency, it becomes possible to measure distances between the proteins and track the aggregation process in real time. The chapter describes the synthesis of a BODIPY-based donor-acceptor pair specifically designed to label the cysteine residues in β-lactoglobulin proteins. In collaboration with the research group of Prof. Andrea Lapini at the European Laboratory for Non-Linear Spectroscopy (LENS) in Florence, early studies on protein aggregation were performed using pump-probe experiments and 2D electronic spectroscopy
Il Transito di oggetti a proposito della collezione kircheriana (1651-1680): mappare la storia materiale tra custodi, prefetti e curatori
No full text Il caso studio della celebre wunderkammer, curata da Athanasius Kircher (Collegio Romano, 1651-1680), è ripercorso attraverso fonti eterogenee che mostrano la possibilità di seguire la storia dei movimenti degli oggetti nella loro rete di relazioni culturali, facendo emergere come attorno al patrimonio collezionistico si stessero formando particolari ruoli e strumenti fin dalla prima età moderna
Dalle Alternative Plant-Based alle Etichette Front-of-Pack: Investigazione della Percezione dei Consumatori e delle Strategie per Diete Sane e Sostenibili
No full textThe transition toward healthier and more sustainable food systems is a pressing challenge of our time, driven by the need to ensure safe, nutritious, and environmentally responsible food for future generations. To support this transition, the present dissertation focuses on two emerging strategies that have shown great potential in fostering healthier and sustainable diets. Specifically, this thesis dives into the promotion of plant-based alternatives, with a focus on meat substitutes, and the implementation of interpretative front-of-pack labeling systems. The research included in this manuscript explores both tools to investigate their potential to influence consumer behavior, improve dietary choices, and support the larger goal of transforming global agrifood systems.
Given the widely recognized environmental and health impact of meat production, plant-based alternatives have emerged as a viable solution to reduce meat consumption. Promoting such products could thus contribute to lowering global greenhouse gas emissions and mitigating public health concerns, while also meeting consumers’ growing demand for more ethical and safer production methods. However, to guarantee the potential of plant-based alternatives, consumers’ acceptance and adoption of such foods is key. In this scenario, this dissertation deepens the understanding of consumer perceptions, motivations, and sensory expectations related to plant-based analogs and examines how these factors can shape purchasing decisions and behavior changes. Special attention is paid to how consumers interpret the sensory qualities of these products and how these perceptions can vary depending on the specific type of product being replaced – whether it is a burger or a hot dog replacement – and on the different consumer segments. The research shows that while consumers may expect plant-based alternatives to be healthy and environmentally friendly options, their motivations for adopting such foods often extend beyond health and sustainability concerns to include the need to meet their sensory expectations. Recognizing these diverse motivations is essential for stakeholders aiming at promoting plant-based alternatives through targeted product development and marketing strategies.
On the other side, front-of-pack labels, particularly interpretative systems such as the Nutri-Score and Eco-Score, represent another key tool for influencing consumer behavior and fostering healthier and more sustainable food choices. Interpretative front-of-pack labels simplify nutritional and environmental information and provide consumers with the necessary information to make timely decisions at the point of purchase. In the context of this dissertation, front-of-pack labels are explored as tools to improve consumers' understanding and also shape their sensory expectations and purchase intentions for plant-based meat alternatives when compared to traditional meat products.
In combining the analysis of the available literature and of novel empirical studies on plant-based alternatives and front-of-pack labels, this PhD dissertation uncovers important insights into the complex relationship between consumer behavior, understanding, sensory perceptions, and visual attention. By enhancing consumer acceptance and understanding, this dissertation also emphasizes the importance of consumer empowerment in driving decisive changes. When provided with the right tools – whether in the form of transparent, accessible information or appealing alternatives to traditional meat products – consumers are better equipped to make food choices that benefit both human health and the environment. Ultimately, as the world seeks to address the challenges posed by climate change, resource scarcity, and public health, promoting plant-based alternatives and effective front-of-pack labeling systems emerges as a promising pathway for aligning consumer behavior with health and sustainability goals. Therefore, by investigating the factors influencing consumer perceptions, acceptance, and behavior, this PhD dissertation supports policymakers, industry stakeholders, and researchers focused on fostering the transition toward healthier and more sustainable food systems.La transizione verso sistemi alimentari più sani e sostenibili rappresenta una sfida urgente del nostro tempo, guidata dalla necessità di garantire cibo sicuro, nutriente e rispettoso dell'ambiente per le future generazioni. A sostegno di questa transizione, la presente dissertazione si concentra su due strategie emergenti che hanno mostrato un grande potenziale nel promuovere diete più sane e sostenibili. In particolare, questa tesi approfondisce la promozione delle alternative plant-based, con un focus sui sostituti della carne, e l'implementazione di sistemi di etichettatura interpretativa front-of-pack. La ricerca inclusa in questo manoscritto esplora entrambi gli strumenti per indagare il loro potenziale nell’influenzare il comportamento dei consumatori, migliorare le scelte alimentari, e sostenere l'obiettivo più ampio di trasformare i sistemi agroalimentari globali.
Dato il riconosciuto impatto ambientale e sulla salute della produzione di prodotti carne, le alternative plant-based sono emerse come una soluzione valida per ridurre il consumo di carne. Promuovere tali prodotti potrebbe quindi contribuire a ridurre le emissioni globali di gas serra e a mitigare i problemi di salute pubblica, rispondendo inoltre alla crescente richiesta dei consumatori di metodi di produzione più etici e sicuri. Tuttavia, per garantire il potenziale delle alternative plant-based, l'accettazione e l'adozione di tali alimenti da parte dei consumatori è fondamentale. In questo scenario, la presente dissertazione approfondisce la comprensione delle percezioni, motivazioni e aspettative sensoriali dei consumatori in relazione agli analoghi plant-based di prodotti animali, ed esamina come questi fattori possano influenzare le decisioni di acquisto e i cambiamenti comportamentali. Particolare attenzione è rivolta a come i consumatori interpretano le qualità sensoriali di questi prodotti e a come tali percezioni possano variare a seconda del tipo di prodotto animale sostituito – che si tratti di un sostituto del burger o di un hot dog – e dei diversi segmenti di consumatori. I risultati mostrano che, sebbene i consumatori possano aspettarsi che le alternative plant-based siano opzioni salutari e sostenibili, le loro motivazioni per adottare tali alimenti spesso vanno oltre le preoccupazioni per la salute e la sostenibilità, includendo la necessità di soddisfare le loro aspettative sensoriali. Riconoscere queste diverse motivazioni è essenziale per gli stakeholders che mirano a promuovere le alternative plant-based attraverso strategie mirate allo sviluppo e marketing di questi prodotti.
D'altra parte, le etichette front-of-pack, in particolare sistemi interpretativi come il Nutri-Score e l'Eco-Score, rappresentano un altro strumento chiave per influenzare il comportamento dei consumatori e promuovere scelte alimentari più sane e sostenibili. Le etichette front-of-pack interpretative semplificano le informazioni nutrizionali e ambientali e forniscono ai consumatori le informazioni necessarie per prendere decisioni rapide al momento dell'acquisto. Nel contesto di questa dissertazione, le etichette front-of-pack vengono esplorate come strumenti per migliorare la comprensione dei consumatori e influenzare le loro aspettative sensoriali e intenzioni di acquisto per le alternative alla carne a base vegetale rispetto ai prodotti tradizionali a base di carne.
Combinando l'analisi della letteratura disponibile e di studi empirici sulle alternative plant-based e sulle etichette front-of-pack, questa dissertazione svela importanti intuizioni sul complesso rapporto tra comportamento dei consumatori, il loro understanding, le percezioni sensoriali e l’attenzione visiva. Rafforzando l'accettazione e la comprensione da parte dei consumatori, questa dissertazione sottolinea anche l'importanza dell'empowerment dei consumatori nel guidare le decisioni alimentari. Quando dotati degli strumenti giusti – sotto forma di informazioni trasparenti e accessibili o di alternative appetibili ai prodotti tradizionali a base di carne – i consumatori posso essere equipaggiati per fare scelte alimentari che avvantaggiano sia la salute umana che l'ambiente. In definitiva, poiché il mondo cerca di affrontare le sfide poste dal cambiamento climatico, dalla scarsità delle risorse e dalla salute pubblica, la promozione delle alternative plant-based e dei sistemi efficaci di etichettatura front-of-pack emerge come un percorso promettente per allineare il comportamento dei consumatori con gli obiettivi di salute e sostenibilità. Pertanto, indagando i fattori che influenzano le percezioni, l'accettazione e il comportamento dei consumatori, questa dissertazione supporta i policymakers, l’industria alimentare, e i ricercatori focalizzati sulla promozione della transizione verso sistemi alimentari più sani e sostenibili
Tick-borne diseases in dogs in Italy: state of the art and future perspectives
No full textTicks are hematophagous arthropods that, often, can be reservoirs of various pathogens, which can consequently be transmitted to the hosts they feed on. During the blood meal, in fact, the tick secretes, through its salivary glands, not only substances useful for adhesion at the site of attachment on the skin, but also any pathogens that spread into the bloodstream of the parasitized animal. In Italy, the most relevant tick species are Ixodes ricinus, Dermacentor reticulatus and Rhipicephalus sanguineus. Regarding pathogens in the Italian context, for dogs the significant ones are: protozoa such as Babesia; viruses such as the Flavivirus that causes tick-borne encephalitis; some bacteria of the order Rickettsiales (Anaplasma spp., Ehrlichia spp. and Rickettsia conorii) and bacteria such as Borrelia spp. of the order Spirochetales. These infectious agents play a fundamental role not only for animal health but also for human health. They, in fact, are transmissible not only to animals, but also to humans, as potential zoonotic agents. This paper aims to present the current situation in Italy regarding the prevalence and distribution of ticks in dogs, the diseases they transmit, and possible prevention strategies. It will also examine factors that could influence the future scenario, such as climate changes that can modify the distribution of ectoparasites, their biological activity, the availability of receptive hosts and, consequently, the transmission of diseases. Another factor to consider is the development of resistance to acaricides, which reduces the effectiveness of products against ticks, exposing animals to infestations and determining the need to identify alternative protection methods, such as vaccines and new active ingredients not subject to resistance. In conclusion, it is essential to investigate and monitor these influencing phenomena to control and prevent the transmission of tick-borne diseases.Le zecche sono artropodi ematofagi che, spesso, risultano serbatoi di svariati patogeni i quali, di
conseguenza, vengono trasmessi agli ospiti su cui i parassiti si nutrono. Durante il pasto di sangue,
infatti, la zecca secerne, tramite le ghiandole salivari, non solo sostanze utili all'adesione nel sito
di attacco sulla cute, ma anche eventuali patogeni che si diffondono nel circolo sanguigno
dell'animale parassitato. In Italia, le specie di zecche più rilevanti risultano essere Ixodes ricinus,
Dermacentor reticulatus e Rhipicephalus sanguineus. Per quanto riguarda i patogeni, invece, nella
realtà italiana, per i cani risultano significativi: protozoi come Babesia; virus come il Flavivirus
che causa l'encefalite trasmessa da zecche; alcuni batteri dell’ordine Rickettsiales (in particolare
Anaplasma spp., Ehrlichia spp. e Rickettsia conorii) e batteri come Borrelia spp. dell’ordine
Spirochetales. Questi agenti infettivi assumono un ruolo fondamentale non solo nell’ambito della
salute animale ma anche nei confronti della sanità umana. Essi, infatti, sono trasmissibili non solo
agli animali, ma anche all’uomo, in quanto potenziali agenti zoonotici. Questo elaborato ha lo
scopo di descrivere in primo luogo la realtà attuale in Italia riguardante la prevalenza e la diffusione
di zecche nei cani e delle relative patologie trasmesse e in secondo luogo i metodi di prevenzione.
Verranno analizzati, inoltre, i fattori che possono potenzialmente influenzare la situazione futura
come i cambiamenti climatici che possono modificare la distribuzione di ectoparassiti, la loro
attività biologica, la disponibilità degli ospiti recettivi e, di conseguenza, la trasmissione di
malattie. Un altro fattore da prendere in considerazione è lo sviluppo di resistenza agli acaricidi che riduce l’efficacia dei prodotti contro le zecche esponendo gli animali alle infestazioni e
determinando la necessità di identificare metodi di protezione alternativi come i vaccini e nuovi
principi attivi non soggetti a resistenza. Si può, quindi, concludere che risulta fondamentale
approfondire e monitorare i citati fenomeni influenzanti per poter controllare e prevenire la
trasmissione di patologie indotte dalle zecch
Distribution, volume and surface variations of milk fat globule in Holstein-Friesian and Reggiana cattle breeds
No full textLa Reggiana è una razza autoctona antica e poco diffusa, nota per la notevole attitudine casearia del suo latte ricco in grasso e proteine, tuttavia, la quantità di latte prodotto per lattazione è nettamente inferiore rispetto alla Frisona, conosciuta per la sua capacità di produrre elevate quantità di latte per singola lattazione come risultato di una selezione genetica perseguita per anni. Il latte di Frisona presenta una minor concentrazione di componenti solidi rispetto a quello di Reggiana determinando una diversa attitudine casearia del latte e una diversa resa in formaggio. Lo studio è stato condotto analizzando 627 campioni di latte individuale: 312 campioni di latte di razza Reggiana e 315 campioni di latte di razza Frisona di cui sono stati determinati: la composizione del latte tramite Milkoscan FT3 e Fossomatic 7DC e la distribuzione e la dimensione dei globuli di grasso tramite Malvern Mastersizer3000. Lo scopo della ricerca è stato quello di determinare in che misura gli effetti quali: razza, ordine di parto e giorni di lattazione incidono sui parametri dimensionali dei globuli di grasso (4,3, d3,2, d2,1, SSA e Span) e in particolare, come la razza influenza le dimensioni e la distribuzione dei globuli di grasso del latte valutando in che modo i risultati ottenuti si riflettono sull'attitudine casearia.
Dai risultati è emersa una notevole significatività dei giorni di lattazione sui parametri dei GDG considerati e relativamente all’effetto razza, i campioni di latte di Reggiana presentano un numero minore di GDG di maggiori dimensioni rispetto a quelli di Frisona che al contrario, presentano un numero maggiore di globuli di piccole dimensioni. Le dimensioni maggiori dei GDG della Reggiana possono influenzare positivamente l’attitudine casearia migliorando consistenza e struttura del formaggio.The Reggiana is an ancient and rare native cattle breed, known for the considerable cheesemaking qualities of its milk, which is rich in fat and protein. However, the amount of milk produced per lactation is significantly lower compared to Friesian which is known for its ability to produce large quantities of milk per lactation because of years of genetic selection; Friesian milk has a lower concentration of solid components than Reggiana one, resulting in lower cheesemaking aptitude and cheese yield. The study was carried out by analyzing 627 individual milk samples, including 312 from Reggiana cows and 315 from Friesian cows. Milk composition was analyzed using the Milkoscan FT3 and Fossomatic 7DC while fat globule size and distribution were evaluated using the Malvern Mastersizer 3000. The aim of the study was to determine the impact of effect such as breed, parity, and stage of lactation in dimensional parameters of milk fat globules (d[4,3], d[3,2], d[2,1], SSA, and Span), with particular attention how the breed effect influences the size and distribution of milk fat globules and how these results impact on cheesemaking properties. The results showed a significant effect of stage of lactation on the considered fat globule parameters. Concerning the breed effect, Reggiana milk samples showed a lower number of larger fat globules whereas Friesian samples showed a higher number of smaller globules. The larger fat globule size observed in Reggiana milk may positively influence cheesemaking performance by improving the consistency and structure of the cheese
Approcci Combinati di Genomica e Metabolomica per Nuovi Metaboliti Specializzati nel Genere Actinoallomurus
No full textIn response to the escalating threat of antimicrobial resistance, research at NAICONS Srl has focused on discovering bioactive natural products (NPs) by investigating the metabolic potential of Actinoallomurus, a relatively unexplored Actinobacteria genus. By integrating traditional cell-based bioassays with advanced metabolomic approaches, the analysis of extracts from 88 Actinoallomurus strains led to the identification of allopeptimicins, a novel family of cyclic depsipeptides with promising antimicrobial activity. Isolated from Actinoallomurus sp. ID145808, allopeptimicins possess a distinctive polyketide-peptide hybrid structure. Structural and bioactivity analyses demonstrated their selective activity against pathogenic bacteria, highlighting their potential therapeutic relevance. Characterization of their biosynthetic gene cluster (BGC) apt revealed gene cassettes for specialized precursors and modular assembly lines with similarities to other known BGCs. This enabled the deposition of apt in the newly released MIBiG 4.0 database, a resource supporting the NP research community in identifying BGCs and their metabolites. Furthermore, an innovative resin-based purification method using lithium chloride elution was developed for selective purification of allopeptimicins A, optimizing yield (35%) and purity (74%). To explore the metabolic potential of Actinoallomurus, a large-scale genomic analysis of 144 strains disclosed both conserved and unique BGCs with low or no similarity to known clusters, facilitating the prioritization of promising BGCs for novel metabolite discovery. Complementing the genomic study, a computational networking approach was implemented to aid large-scale data annotation. The Molecules Gateway, a proprietary database of 150k annotated molecules, enables efficient dereplication and compound identification in complex microbial extracts. This resource supported the development of a semi-automated workflow for molecular network annotation, laying a foundation for prioritizing novel NPs. Applied to 340 Actinoallomurus extracts, this workflow identified numerous genus-specific, uncharacterized molecular families, including one exclusive to strain M23/ID150205. Integration with genomic data enabled the identification of a novel BGC, exclusive to this strain, leading to the discovery of novel compounds currently under structural characterization. This scalable framework places Actinoallomurus as a promising source for novel metabolites and provides a model for exploring underexplored microbial genera to uncover new chemical scaffolds.Di fronte alla crescente minaccia della resistenza antimicrobica, la ricerca presso NAICONS Srl si è concentrata sulla scoperta di prodotti naturali (NP) bioattivi, esplorando il potenziale metabolico di Actinoallomurus, un genere poco studiato fra gli Actinobacteria. Integrando test tradizionali con approcci metabolomici avanzati, l'analisi di estratti da 88 ceppi ha portato all'identificazione delle allopeptimicins, una nuova famiglia di depsipeptidi ciclici con attività antimicrobica promettente. Isolate da Actinoallomurus sp. ID145808, le allopeptimicins presentano una peculiare struttura ibrida polichetidico-peptidica. Le analisi strutturali e di bioattività hanno rivelato un’attività selettiva contro batteri patogeni, evidenziandone la rilevanza terapeutica. La caratterizzazione del cluster biosintetico (BGC) apt ha evidenziato la presenza di cassette geniche dedicate a precursori specializzati e linee di assemblaggio modulari con similarità con altri BGC noti. Ciò ha consentito il deposito di apt nel database MIBiG 4.0, una risorsa per l’identificazione di BGC e relativi metaboliti. È stato inoltre sviluppato un innovativo metodo di purificazione su resina con eluizione a cloruro di litio per la purificazione selettiva delle allopeptimicins A, ottimizzando resa (35%) e purezza (74%). Per esplorare il potenziale metabolico di Actinoallomurus, un'analisi genomica su 144 ceppi ha rivelato BGC conservati e unici, con scarsa o nessuna similarità con cluster noti, facilitando la prioritizzazione di BGC promettenti per la scoperta di nuovi metaboliti. A complemento dello studio genomico, è stato implementato un approccio computazionale di networking per agevolare l'annotazione di dati su larga scala. Il Molecules Gateway, un database proprietario con 150k molecole annotate, consente un’efficace dereplicazione e identificazione di composti in estratti microbici complessi. Questa risorsa ha permesso lo sviluppo di un workflow semi-automatizzato per l’annotazione dei network molecolari, ponendo le basi per la prioritizzazione di nuovi NP. Applicato a 340 estratti di Actinoallomurus, il workflow ha rivelato numerose famiglie molecolari non caratterizzate, tra cui una esclusiva del ceppo M23/ID150205. L’integrazione con dati genomici ha permesso di individuare un nuovo BGC, esclusivo di questo ceppo, portando alla scoperta di nuovi composti attualmente in fase di caratterizzazione strutturale. Questo approccio scalabile posiziona Actinoallomurus come fonte di nuovi metaboliti e offre un modello per l’esplorazione di generi microbici poco studiati alla ricerca di nuove strutture chimiche
Integrated green chemistry approaches for the development of PCSK9 inhibitors with multiple pharmacological applications
No full textThis thesis integrates green chemistry principles with the development of novel small-molecule PCSK9 inhibitors, in a sustainable medicinal chemistry effort. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a critical drug target, widely recognized for its role in hypercholesterolemia treatment and increasingly investigated for its involvement in other pathological conditions, including infections, neurodegenerative diseases, and cancer. Despite its significant therapeutic potential, no small-molecule PCSK9 inhibitors are currently available on the market, underscoring the challenges in their development and emphasizing the importance of the research objectives pursued in this work.
In the work herein described, I have employed both phenotypic and target-based drug discovery (PDD and TBDD) approaches to identify and optimize novel PCSK9i chemotypes. A sustainable medicinal chemistry perspective has guided the synthesis of these compounds, utilizing green methodologies such as late-stage functionalization (LSF), electrochemistry, multicomponent reactions (MCR), and microwave-assisted synthesis. The resulting compounds were evaluated for their pharmacological applications as lipid-lowering and neuroprotective agents.
The PDD studies were conducted at the University of Parma and led to the identification of the 4-amino-2-pyridone as a promising anti-PCSK9 chemotype through phenotypic screening. This was followed by a hit-expansion campaign, early lead identification, and subsequent lead optimization to improve the metabolic stability. Lead optimization was supported by different green chemistry tools, such as electrochemistry and MCR to perform LSF of the early lead compound. Moreover, scaffold hopping based on the early lead led to the discovery of 2-aminothiazoles as a novel promising anti-PCSK9 scaffold.
The in silico TBDD studies were conducted as Remote Company Training from the University of Pisa under the supervision of Prof. Tiziano Tuccinardi, with remote supervision by Dr. Sharon Bryant, CEO of InteLigand. These efforts involved a virtual screening protocol comprising docking studies, molecular dynamics simulations, and pharmacophore generation. This process resulted in the identification of a third active chemotype that was chemically expanded at the University of Parma.
To further advance the understanding and application of electrochemistry as a green chemistry methodology, I undertook a three-month research placement in the laboratory of Prof. Kevin Lam at the University of Greenwich (UK). During this period, I worked on the development and scope exploration of an electrochemical protocol for the hydrogenation and deuteration of organic compounds
What remains: visual notes around the table
No full textIl progetto nasce da una serie di fotografie analogiche scattate durante pasti in famiglia o con amici. Osservando queste immagini, ho iniziato a riconoscere il valore personale di quei momenti e i dettagli che spesso passano inosservati: cosa mangiamo, quando mangiamo, con chi condividiamo il pasto e quanto tempo gli dedichiamo. Per questo motivo ho deciso di analizzare meglio ogni fotografia, affiancandola a un’infografica che rappresenta visivamente alcuni dati significativi: il momento della giornata, la tipologia di cibo, il numero di persone presenti e la relazione che ognuna di loro ha con me. Il progetto si sviluppa come un racconto visivo in cui immagini e visualizzazioni grafiche si alternano e si completano, mettendo in luce ciò che rimane dopo la fine del pasto. L’obiettivo è da un lato fissare il ricordo dei momenti condivisi con le persone a me care, e dall’altro avere uno strumento per osservare e analizzare le mie abitudini alimentari. Non si tratta di proporre nuove soluzioni progettuali, ma di offrire un diverso modo di osservare e interpretare la quotidianità. The project originates from a series of analog photographs taken during meals shared with family and friends. While observing these images, I began to recognize the personal value of those moments and the details that often go unnoticed: what we eat, when we eat, with whom we share the table, and how much time we devote to the meal. For this reason, I decided to examine each photograph more closely, pairing it with an infographic that visually represents several meaningful data points: the time of day, the type of food, the number of people present, and each person’s relationship to me. The project unfolds as a visual narrative in which images and graphic visualizations alternate and complement one another, highlighting what remains once the meal is over. The aim is, on the one hand, to preserve the memory of moments shared with the people I care about, and on the other, to provide a tool for observing and analyzing my eating habits. It is not intended to propose new design solutions, but rather to offer a different way of observing and interpreting everyday life
Data-driven and knowledge-based analytical valorization of natural products for sustainable and innovative applications
No full textAnalytical chemistry plays a key role in the valorization of natural products. When combined with sustainable technologies such as green biorefineries, the stakes are even higher. Valorization has a broad meaning. For this reason, this work is divided into five different chapters. Three different levels of valorization are discussed. The introduction (chapter one) begins with a description of the biorefinery process, focusing on Medicago sativa. Then the analytical tools, the data analysis strategies, and their combination are discussed. Chapter two is a description of the proteomic and phenolic characterization of biorefinery products. The valorization starts from here. Design of Experiments (DoE) was used to identify the best combinations of factors to optimize the extraction procedures. These were then evaluated and modified according to their biocompatibility with cells. The profile of proteins, protein hydrolysates, and metabolites was defined using liquid chromatography with tandem mass spectrometry. The second level is the investigation of the biological effects of complex natural mixtures. Specifically, the pro-apoptotic activity was studied on colorectal cancer cells as an epithelial proliferation model. Data-driven and knowledge-based approaches were used to generate hypotheses about their mechanisms of action. Chapter three is divided into two sections. The first focuses on Medicago sativa biorefinery products. The second focuses on protein extracts from four quinoa varieties. Overall, the basic idea behind this chapter was to demonstrate the combination of data modeling and critical thinking as a powerful tool for transforming raw data into understanding, new perspectives, and knowledge. The third level is about the optimization of the biorefinery process. In the fourth chapter, near-infrared spectroscopy was used to develop regression and classification models for process monitoring. Despite the satisfactory results, this chapter aims to highlight the tension between optimization and generalization. Especially when it comes to small datasets (typical of laboratory and pilot scale). Finally, chapter five provides a summary of the results and future perspectives. In conclusion, this dissertation aims to present different valorization strategies. But at the same time, all the challenges that can arise and a way to deal with them. Especially using the different paradigms of data analysis