Synthesis in millireactor system and stability of intermediates for the functionalization of imidazole

This Master thesis presents the results obtained in the curricular traineeship, carried out within the laboratories of the Department of Chemistry of the University of Bergen, during the Erasmus period, and within the Department of Industrial Chemistry of the University of Bologna. The project followed in Bergen concerned the synthesis of key intermediates used for the functionalization of the backbone of imidazole, using N,N'- diiodo-5,5-dimethylhydantoin (“DIH”) as an iodinating agent, and employing an innovative kind of chemical reactor: the “Multijet Oscillating Disc Millireactor” (MJOD Reactor). Afterwards, the work performed in Bologna consisted in verifying the stability in solution of the above mentioned N,N'-diiodo-5,5-dimethylhydantoin utilising spectrophotometric techniques and High Performance Liquid Chromatography analyses (HPLC).

Synthesis and functionalization of a lactam-pyrazole molecular scaffold as a promising anticancer compound

The importance of pyrazole and lactam-based molecules in medical and pharmaceutical fields is underlined by the multitude of active ingredients on trade, such as Sildenafil or Apixaban, by Pfizer. In this work, a synthesis of an organic molecule with promising anticancer activity has been developed. This molecular scaffold is characterized by a δ-lactam-fused pyrazolic core, with a well-known biological activity and amenable of further functionalization. The synthetic strategy adopted for the obtainment of the core was based on a 1,3-dipolar cycloaddition of a nitrilimine with an α,β-unsaturated δ-lactam. Secondly, in order to give the final compound an elevated pharmacological activity, a functionalization with a double “side chain”, namely molecular fragment able to improve the interaction with particular biological receptors, was achieved. The target compound was thus obtained, with a highly convergent synthesis, and will be tested for antiproliferative activities towards different cellular lines.

Development of tandem C-H borylation/functionalization procedures for late stage functionalization of compounds

The development of procedures for the iridium catalyzed C-H borylation of 1-aryl pyrazolopyrimidines and 1-aryl indazoles is reported. Investigation on the activity of the catalyst revealed the combination of an iridium (I) precursor and tetramethylphenantroline as the best catalytic system. Moreover, the procedures are regioselective resulting in the selective borylation of different C-H bonds within the substrates. The application of C-H borylation to late stage functionalization is demonstrated: a biologically active compound in AstraZeneca's project underwent tandem borylation/oxidation reaction, in order to obtain a functionalized product containing an OH group.

Influence of free-radical functionalization on non-woven filtering media for medical application

Nowadays the leukodepletion is one of the most important processes done on the blood in order to reduce the risk of transfusion diseases. It can be performed through different techniques but the most popular one is the filtration due to its simplicity and efficiency. This work aims at improving a current commercial product, by developing a new filter based on Fenton-type reaction to cross-link a hydrogel on to the base material. The filters for leukodepletion are preferably made through the melt flow technique resulting in a non-woven tissue; the functionalization should increase the stability of the filter restricting the extraction of substances to minimum amount when in contact with blood. Through the modification the filters can acquire new properties including wettability, surface charge and good resistance to the extractions. The most important for leukodepletion is the surface charge due to the nature of the filtration process. All the modified samples results have been compared to the commercial product. Three different polymers (A, B and C) have been studied for the filter modifications and every modified filter has been tested in order to determine its properties.

(In)Visibili. Difficoltà, scelte e implicazioni nella mediazione nazionale dei personaggi non-binary

Con il progressivo aumentare del numero di personaggi non-binary nelle serie televisive in lingua inglese, dal punto di vista della mediazione nazionale italiana si va a delineare un interessante campo di studio, determinato dallo scontro fra la predilezione, da parte di questi personaggi, di pronomi ed espressioni neutre e la struttura grammaticale italiana, basata, invece, sull’esclusiva contrapposizione fra maschile e femminile. Il presente elaborato, allora, si pone l’obiettivo di individuare, attraverso una selezione di casi di studio, le difficoltà che sorgono automaticamente nel momento della realizzazione dell’edizione italiana di queste serie, le strategie adottate ai fini di rendere neutro il linguaggio italiano e le loro implicazioni nei confronti dei personaggi non-binary. Il metodo di studio consiste nel confronto fra la versione originale e l’edizione italiana (comprensiva di doppiaggio e sottotitoli) delle battute relative ai personaggi non binari di riferimento, con conseguente analisi delle differenze e somiglianze rilevate. I tre casi presi in considerazione nel corso della trattazione (Sex Education, One Day at a Time e Grey’s Anatomy) permettono, in definitiva, di individuare come rischio primario l’invisibilità del non binarismo di genere agli occhi e alle orecchie degli spettatori italiani e, così, lo snaturamento dell’intento e del valore dell’edizione originale.