Abduvakhidov, Avazbek (2025) Synthesis and structural characterization of molecules with specific biological activity. [Tesi di dottorato]

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Abstract

The doctoral research presented in this thesis lies at the intersection of materials science, analytical chemistry, and organic synthesis, moving across different scientific contexts but united by a common objective: the design, preparation, and characterisation of functional materials and molecules tailored for specific purposes, ranging from biomedical applications to analytical detection. The first part of this research was carried out in collaboration with several research groups at the University of Naples Federico II, under the coordination of Professor Carlo Altucci (Department of Medical Physics). The work forms part of a broader interdisciplinary project aimed at the development and functionalisation of nanosheet materials with tailored organic molecules to enhance their performance in biomedical applications. Particular attention was devoted to the use of environmentally sustainable approaches for nanosheet production. MoS₂ and WS₂ were exfoliated in liquid phase using Cyrene, a bio-derived, low-toxicity solvent fully consistent with the principles of green chemistry. This strategy allowed the preparation of stable dispersions of mono- and few-layer nanosheets without resorting to harmful solvents such as NMP or DMF. In parallel, I worked on the synthesis and characterisation of antimonene nanosheets non-covalently functionalised with cyclodextrins, designed to improve their colloidal stability and biodegradability, thereby evaluating their potential suitability for biomedical applications. During these studies, I became familiar with key structural characterisation techniques, including Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and X-ray Photoelectron Spectroscopy (XPS). The extensive analysis and interpretation of experimental data strengthened my ability to address critical aspects related to the structural investigation of complex materials, from sample preparation to the correlation of experimental findings with literature data. These activities are presented in Part I of the thesis, which is composed of three chapters. Chapter 1 provides a general introduction to nanomaterials, with particular emphasis on transition metal dichalcogenides (TMDs) and on antimony-based nanomaterials, outlining the main production and functionalisation methodologies. Chapter 2 describes the results obtained from the green exfoliation and characterisation of MoS₂ and WS₂ nanosheets, while Chapter 3 reports the outcomes related to the preparation, functionalisation with cyclodextrins, and biodegradation behaviour of antimonene nanosheets. My expertise in the design and preparation of functional systems expanded through participation in the European project Blueshellfish (Solutions to prevent and mitigate the impacts of HABs in Aquaculture and Fisheries, in the context of global warming). The project focuses on developing strategies to prevent and mitigate the impact of harmful algal blooms (HABs) in aquaculture and fisheries. Under the supervision of Dr. Mònica Campàs, I joined the research line dedicated to the design of biosensing systems for marine toxins, focusing on the use of nucleic acid–based recognition elements (aptamers) as alternatives or complements to antibodies in analytical assays. Within this context, my research activities were devoted to the development of aptamer-based biosensors for the detection of saxitoxin (STX), a potent marine neurotoxin of high regulatory and ecological relevance. The work was performed in the framework of a secondment agreement between the University of Naples Federico II and IRTA. After synthesizing biotinylated DNA aptamers for STX by means of an automated oligonucleotide synthesizer and the phosphoramidite method, I applied these aptamers in various analytical formats, including microplate, electrochemical, and magnetic bead-based systems, exploring their potential as recognition elements in colorimetric and hybrid antibody–aptamer assays. The assays did not yet achieve complete functional detection of STX, and further studies will be fundamental in identifying the critical parameters affecting aptamer performance, such as the surface chemistry of the different applied supports and the preservation of aptamer folding upon immobilisation. In parallel, I contributed to an interlaboratory validation study (Ring Test) developed by the Interfibio Research Group (University Rovira i Virgili, Spain), in collaboration with IRTA and the Hellenic Centre for Marine Research (HCMR, Greece). The study assessed the reproducibility of a hybrid aptamer-antibody lateral flow assay (LFA) for tetrodotoxin (TTX) detection. These activities are presented in Part II of the thesis, composed of three chapters. Chapter 4 introduces the aptamers and their use in biosensing, with an overview of optical and electrochemical systems currently employed for saxitoxin detection. Chapter 5 describes the experimental approaches adopted during my research period at IRTA, focusing on saxitoxin detection using aptamer-based biosensing assays. Chapter 6 presents the interlaboratory study on the aptamer-antibody lateral flow assay for TTX. Part III of the thesis focused on the synthesis and structural characterization of small molecules having specific properties. In this context, my work involved the synthesis, optimisation, and characterisation of new azobenzene derivatives, designed to achieve efficient visible-light responsiveness and enhanced stability of the cis isomer in aqueous environments. These studies provided important insight into the relationship between molecular structure and photo-chemical behaviour. The overall results are discussed in Chapeter 7. In parallel, I actively participated in a multidisciplinary study aimed at the discovery and development of bioactive small molecules capable of modulating protein–protein interactions (PPIs), which play a central role in cellular signalling and disease progression. The results are presented Chapter 8.

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