CTC https://hdl.handle.net/10955/32 2026-04-29T23:33:13Z 2026-04-29T23:33:13Z Ponte, Fortuna Andò, Sebastiano Sicilia, Emilia https://hdl.handle.net/10955/5597 2025-03-26T08:50:23Z 2020-02-05T00:00:00Z

Anticancer drugs: a detailed computational analysis of "non classical" compounds mechanism of action Ponte, Fortuna; Andò, Sebastiano; Sicilia, Emilia Metal containing drugs have attracted an enormous deal of interest for their use in cancer therapy. Transition metal compounds’ richness offers extraordinary opportunities for the design of anticancer compounds, possessing pharmacokinetic properties inaccessible to purely organic compounds. The most successful and evident proof of their pivotal role is represented by cisplatin that, together with its carboplatin and oxaliplatin derivatives, continues to be routinely used worldwide in clinical practice. However, it is well known that the use of such drugs for fighting cancer is accompanied by severe side effects and intrinsic or acquired resistance that drastically limit their successful action. Therefore, decades of research efforts have been devoted to the search and the synthesis of safer and more effective and selective agents, either containing platinum or alternative metals, acting with similar or different mechanisms. In order to accomplish this aim is of decisive importance the elucidation of the mechanism of action of the drugs. Molecular simulations, or in silico experiments, are able to provide detailed information at atomistic resolution, rarely accessible to experiments, that can complement laboratory experiments. The increasing accuracy of computational approaches and the growing performance of computer performance, allow to properly describe reaction paths and involved molecular orbitals, calculate electronic properties, simulate spectra without any limitation except those connected with the adopted level of theory and compuatational protocol. The main aim of the present work was the detailed investigation, in the framework of the Density Functional Theory, of the mechanism of action of “non classical” platinum and transition metal non-platinum compounds, for some of them in collaboration with experimentalists, and the rationalization of their behaviors. In the next paragraphs all the studied systems will be shortly described together with the motivations that have prompted us to study such systems. Both “non classical” platinum(IV) prodrugs, non-platinum drugs and photoactivatable Pt(II) and Pt(IV) complexes have been examined. In the development of new platinum-based anticancer drugs, is of great interest the emerging class of "dual action" Pt(IV) prodrugs that, undergoing a reductive elimination process, which is the key step for their activation, are able to release the active Pt(II) complexes and bioactive axial ligands that together lead to cell death. Indeed, the two axial ligands, in turn, can be chosen to possess physico-chemical and biopharmaceutical properties or even facilitate the incorporation into a drug delivery system. According to the research lines mentioned above, the use of drug delivery systems has also grown, and many different strategies have been examined to encapsulate platinum drugs within macromolecules, including macrocyclic species, which are responsible for creating supramolecular host-guest structures. The encapsulation slows down and prevents the drug degradation by proteins and peptides. One of the most widely studied class of synthetic supramolecular macrocycles are Calix[n]arenes (CX), whose property, as molecular hosts and delivery systems, are of increasing interest. Photodynamic Therapy (PDT) is a non-toxic therapeutic technique, clinically approved and minimally invasive, used for the treatment of several types of cancers based on the generation of reactive oxygen species (ROS), that acts as cytotoxic agents. In PDT applications three components are required: a photosensitizer (PS), a light of a specific wavelength and tissue oxygen. A promising approach to increase the effectiveness of anticancer therapy is the combination of multimodal treatment methods into a single system. Recently, a strategy has been proposed providing the possibility to combine the classical Pt-based chemotherapy with photodynamic therapy (PDT) treatment. This approach involves the functionalization of a photosensitizer (PS) with a therapeutic drug such as cisplatin-like compounds. Università della Calabria. Dipartimento di Chimica e Tecnologie Chimiche. Dottorato di ricerca in Medicina Traslazionale. Ciclo XXXII

2020-02-05T00:00:00Z Amuso, Roberta Critelli, Salvatore Gabrele, Bartolo Veltri, Lucia https://hdl.handle.net/10955/5506 2024-11-25T08:06:18Z 2021-10-28T00:00:00Z

New Catalyzed Approaches For The One-Step Synthesis Of High Value-Added Products Amuso, Roberta; Critelli, Salvatore; Gabrele, Bartolo; Veltri, Lucia Heterocyclic compounds play an important role in synthetic and bioorganic chemistry, as they represent a structural motif in a large number of biologically active natural and non-natural compounds. The synthesis of new heterocycles possessing biological activity and the development of innovative and accessible synthetic pathways are currently a very widespread research area. In the present PhD thesis is reported the development of new synthetic, simple and innovative methodologies in one step for the direct formation of high value-added compounds by the catalytic activation of simple building blocks, CO and CO2. CO is a simplest and most available C-1 unit, which meets the requirements of “atom economy”, step economy and “green chemistry”; the possibility to synthesize molecules of important pharmacological interest by a direct carbonylation procedure involving the use of carbon monoxide represent a very attractive alternative synthetic approach. CO2 is the main component of greenhouse gases, responsible for the increase in the earth's temperature and anomalous climate changes. Thus, post-combustion COIn fact, carbon dioxide can be considered as a ubiquitous, cheap, abundant, non-toxic, non-flammable and renewable C1 source, which has great importance from the viewpoint of both environmental protection and resource utilization. In the first chapter is reported a new example of an additive cyclocarbonylation process leading to 1-thia-4a,9-diazafluoren-4-ones, an important class of polyheterocyclic compounds known to possess important pharmacological activities. Part of this PhD was spent at Leibniz Institute for Catalysis in Rostock University. Here, ruthenium PNP pincer complexes bearing supplementary cyclometalated C,N-bound ligands have been prepared and fully characterized for the first time. The advantages of the new catalysts are demonstrated in the general green α-alkylation of ketones with alcohols following a hydrogen autotransfer protocol. Furthermore, other cyclometalated ruthenium complexes bearing bidentate ligand were obtained for methylation of anilines with methanol to selectively give N-methylanilines. The hydrogen autotransfer procedure has been applied under mild conditions (60 °C) in a practical manner (NaOH as base).2 capture and its conversion into high value-added chemicals are integral parts of today’s green energy industry. UNIVERSITA’ DELLA CALABRIA Dipartimento di Chimica e Tecnologie Chimiche Scuola di Dottorato in Scienze e Ingegneria dell’Ambiente, delle Costruzioni e dell’Energia (SIACE). Ciclo XXXIII

2021-10-28T00:00:00Z Ashimova, Saltanat Zhandarbekovna Cerra, Maria Carmela Rossi, Cesare Oliverio Burkhanbaevich, Teltayev Bagdat https://hdl.handle.net/10955/5503 2024-09-23T15:08:09Z 2021-04-08T00:00:00Z

Green biomaterials and advanced technologies for road pavements Ashimova, Saltanat Zhandarbekovna; Cerra, Maria Carmela; Rossi, Cesare Oliverio; Burkhanbaevich, Teltayev Bagdat The main objective aims at developing methodologies and new biomaterials for the sustainability assessment of “green bituminous mixtures”. “Green bituminous mixtures” is used in the context as a general term for all types of bituminous mixtures in which specific materials or technologies are used with the aim of reducing the environmental impact and of reducing health risks of workers. In the present research new bioadditives were developed and tested to improve the adhesion between bitumen and stones, to modify the rheological characteristic of the bitumen as well as rejuvenating properties of the bitumen. Dottorato di Ricerca in Scienze della Vita. CICLO XXXII

2021-04-08T00:00:00Z Porto, Michele Cerra, Maria Carmela Rossi, Cesare https://hdl.handle.net/10955/5495 2024-07-12T10:51:30Z 2021-01-01T00:00:00Z

Production of new bituminous materials (ecobinders)by recycling waste oil and rubber from end-of-life tire ("Crumb Rubber") Porto, Michele; Cerra, Maria Carmela; Rossi, Cesare Nowadays the main problems faced by applied research and industry are towards environmental issues such as global warming, carbon footprint, reduction of greenhouse gas emission amongst others. The Kyoto Treaty was developed as a result in 1997 to setting the objective for European countries to develop policies and technologies in order to meet greenhouse gas reduction requirements. In this light, the asphalt industry accordingly implemented measures to facilitate eco-friendly operations. Examples of some of these measures include the introduction of the use of Warm Mix Asphalt (WMA) and Reclaimed Asphalt Pavement (RAP) which reduce production costs and reduce CO2 emissions. Another initiative used to address environmental problems is resource conservation which has made the use, recovery and recycling of resources more practical and effective in not only reducing production costs but also in making a regenerative circular economy. An example of this initiative is an innovation called End of Waste (EoW) product through which waste is converted into a new product and it is proving very practical and effective in recent times. The End of Waste (EoW) criteria means recovery and treatment processes under which waste could be converted in a new potential product. In particular, according to the European normative the main requirements for a given waste - possibly treated by industrial processes - to satisfy the EoW qualification are the following: a) the substance or object is intended to be used for specific purposes; b) there is a market or demand for this substance or object; c) the substance or object meets the technical requirements for the specific purposes and complies with the existing legislation and standards applicable to the products; d) the use of the substance or object will not lead to overall negative impacts on the environment or human health (in accordance with the Substance of Very High Concern (SVHC) list) From this perspective, the reuse of opportunely re-refined exhausted oils from automobile and industrial hydraulic applications - that have become unfit for the use for which they were originally intended - completely fulfil the circular economy goals. This PhD thesis deals with the conversion of End of Waste Product (EoW) in the form of Re-refined Engine Oil Bottom (REOB) obtained from exhausted oil regeneration processes – through the addition of recycled industrial waste materials - to high performing bituminous binder suitable for use in asphalt mix production. This can save the asphalt industry an even larger amount of resources if it is normalized to practice using this new potentially revolutionary binder together with Reclaimed Asphalt Pavement (RAP) which reduces the need for virgin aggregates in asphalt mix production. Indeed, in the present work asphalt concrete samples have been obtained by using 100 % Reclaimed Asphalt Pavement (RAP) aggregates. The asphalt concrete samples thus obtained underwent testing in order to study their behaviour with the goal to substitute virgin aggregates that are commonly employed in asphalt pavement. This would allow to reach the standards of most of the European countries where RAP is already used in the range of 70-90%, while up to now in Italy a maximum of 30% of RAP is used in the Hot Mix Asphalt (HMA) and Warm Mix Asphalt (WMA). The aged and more brittle bituminous binder that coats the aggregates limits the use of RAP material as it stiffens the resulting asphalt mixtures making the pavements more brittle and sometimes more prone to cracking especially at low temperatures. To overcome this problem a rejuvenating agent could be used. Dottorato di Ricerca in SCIENZE DELLA VITA. Ciclo XXXIII

2021-01-01T00:00:00Z