DSpace Collection:https://hdl.handle.net/1889/6732023-11-08T04:43:58Z2023-11-08T04:43:58ZMultivalent peptido and glycocalixarenes as ligands for microorganismsVezzoni, Carlo Albertohttps://hdl.handle.net/1889/54042023-06-22T14:27:08Z2023-01-01T00:00:00ZTitle: Multivalent peptido and glycocalixarenes as ligands for microorganisms
Authors: Vezzoni, Carlo Alberto
Abstract: The present thesis work deals with the design and synthesis of novel calixarene-based multivalent ligands tailored to interact with proteins exposed on the external membrane of different microorganisms. The calixarene macrocycle was chosen as central core of these multivalent ligands because of the efficient methods known for its selective functionalization either at the upper or lower rims and for the possibility to easily modulate, at will, the geometry of the exposed ligating units. This last feature is particularly important when designing multivalent systems for the recognition of biological macromolecules, since it allows to develop ligands of increased efficiency and selectivity.
After a general introduction on calixarenes for protein targeting, the first chapter reports the results of a project aimed at obtaining peptidocalix[4]arenes for the inhibition of the SARS-CoV-2 virus. Our goal was to synthesize ligands able to bind to the virus Spike protein and potentially able to prevent its interaction with its host cell receptor and to block the infection process. This work was triggered by a molecular modelling study to screen in silico potential ligands and was followed by the synthesis of some of the selected compounds and by their tests on a model of the virus.
In the second chapter is reported the work performed at the University of Grenoble, where the candidate spent a 6-months research period in the group of prof. Olivier Renaudet. During this period, the attention was focused on the design and synthesis of fucosylated calix[4]arenes for the interaction with three different lectins: Aspergillus fumigatus lectin, Burkholderia ambifaria lectin and LecB from Pseudomonas aeruginosa. In parallel to the synthesis of more classical fucosylated calixarenes, we also synthesized a novel “superstructure” based on a central calix[4]arene core in cone geometry functionalized at the upper rim with four cyclodecapeptides, each of them decorated with four units of fucose, resulting in a peculiar hexadecavalent ligand. All the synthesized compounds were tested in ITC experiments to study their affinity towards the three lectins.
Finally, in the last chapter it is described the preparation of calix[4]arene-based ligands designed for the selective recognition of Gram-positive, Gram-negative and Mycobacteria. To develop ligands capable of discriminating among these three bacterial groups we targeted peculiar epitopes or proteins exposed on the surface of their cell wall. The obtainment of selective ligands for each of these classes of bacteria could be an important aid towards the development of new bacterial sensor devices useful, to medical doctors, for the rapid selection of the appropriate antibiotic, preventing the administration of broad-spectrum drugs that are among the main causes of the spread of antibiotic resistance. Moreover, these bacteria ligands could even find applications for the preparation of novel targeted antibacterial drugs.2023-01-01T00:00:00ZCellulose nanocrystals: from extraction to applicationsPotenza, Mariannahttps://hdl.handle.net/1889/54032023-06-22T14:24:58Z2023-01-01T00:00:00ZTitle: Cellulose nanocrystals: from extraction to applications
Authors: Potenza, Marianna
Abstract: In this research the possibility of extracting nanocellulose from different sources, such as cotton, wastepaper and waste from agricultural production was studied. Particular attention has been paid to the characterization of the obtained products to establish the morphology, the type of polymorph and the degree of crystallinity of each sol. Some surface functionalizations of the nanocrystals were presented, with particular attention to the presence of the newly added functional groups. The ability of nanocellulose to act as a carrier for silver nanoparticles, whose biocidal activity against gram + and gram - bacteria, has been reported, have been also studied. Successively, the possibility to use nanocellulose in different fields, such as cultural heritage, environmental and building was investigated. Nanocellulose was used as coating for ligno-cellulosic materials, such as paper and painted canvas, with a promising consolidating ability. The possibility to not alter the substrate chromatically, before and after accelerated artificial ageing cycles, and the mechanical properties of the treated substrates have been also evaluated. These characteristics were compared with those relating to Aquazol 500, a commercial product still used in restoration. To develop the research in medical and environmental fields, two different matrices based on nanocellulose were proposed. For the first application, 3D printed hydrogel scaffolds made of nanocellulose and alginate, mixed with silver nanoparticles to promote antimicrobial action were studied. For the second type of application, three-dimensional hydrogel scaffolds, made of carboxymethylcellulose mixed with nanocellulose, obtained by freeze-thaw method, for the removal of heavy metals in water were presented.
Finally, the research activity was focused on the study of innovative eco-compatible geopolymer mortars and plasters. The present research mainly focuses on the possibility of replacing the liquid alkaline activator. For the development of binders, mortars and plasters, parameters such as workability (consistency, plasticity and cohesion) must be considered. One-part binders were investigated: the powder precursors were varied to evaluate the product with best performance. After choosing the binder, mortars and plasters were developed. Then, for both materials, several formulations were proposed. Particular attention has also been paid to the use of various natural additives, such as starch and cellulose, due to their adhesive properties and rheological modifiers, respectively, which influence the properties of the fresh and hardened mortar: as the type and quantity of additives vary, workability, adhesion to the substrate and mechanical resistance were evaluated. Finally, mortars and plasters were applied on autoclaved aerated concrete blocks: the correction time and the adherence were evaluated. All products were fully characterized, to assess the chemical, physical and mechanical properties.2023-01-01T00:00:00ZOrganic dyes in condensed media: photophysics beyond gas phasePhan Huu, Dang Khoa Andreahttps://hdl.handle.net/1889/54022023-06-22T14:23:05Z2023-01-01T00:00:00ZTitle: Organic dyes in condensed media: photophysics beyond gas phase
Authors: Phan Huu, Dang Khoa Andrea
Abstract: The simulation of dyes in condensed phase is a daunting, but rewarding task with enormous practical implications. For example, in the field or organic opto-electronics, understanding the interplay between an organic dye and the host in which it is dispersed may lead to the optimal tuning of the properties of the device, in a smart matrix approach. By its nature, the computational study of large disordered systems requires reliable approximations. To this aim, effective models for the dye and the medium are useful to rationalize the behaviour of complex systems.
The first part of this work addresses a very general issue, how the electronic degrees of freedom of the medium, i.e. the medium polarizability, affect the properties of the dye.
Three coupling schemes can be adopted to describe the interaction between the medium and an embedded dye:
- a non-adiabatic coupling that treats the medium degrees of freedom on the same foot as the electronic degrees of freedom of the dye;
- an adiabatic coupling that neglects the kinetic energy associated to the medium degrees of freedom; - an antiadiabatic coupling that consider an instantaneous response of the medium degrees of freedom to relevant events occurring in the dye.
The non-adiabatic approach is of course the most accurate, but, apart from its computational cost, it requires a detailed knowledge of the dynamics of the medium. The adiabatic and antiadiabatic approaches instead allow to renormalize away the medium degrees of freedom leading to effective solvation models, and, quite naturally apply when the medium degrees of freedom are much slower and faster, respectively, that the relevant degrees of freedom of the dye.
Despite their widespread use and computational efficiency, current implementations of implicit solvation models struggle to accurately describe the phenomenon, leading to a proliferation of approaches, that often yield widely different, and sometimes even unphysical, results.
Indeed, in current implementations of implicit solvation models, the electronic degrees of freedom of the medium are treated in the adiabatic approximation, and then fails to account for the medium polarizability.
To address this problem, in the framework of the reaction field model, we derive and validate an antiadiabatic Hamiltonian. We demonstrate that the adiabatic approximation to the medium polarizability, as implemented in widespread implicit solvation models, fails dramatically when applied to dyes for thermally-activated delayed fluorescence (TADF), where, depending on the system, an unphysical negative singlet-triplet gap is predicted.
The second part of this work is focused on modelling TADF dyes in liquid solvent and amorphous matrices. DMAC-TRZ is chosen as a representative system for twisted donor-acceptor dyes, and is modelled accounting for four diabatic electronic states, an effective molecular vibration and one effective torsional vibration. The model is parametrized ab initio and validated against experimental spectra in solution. Inter-system crossing (ISC) and reverse inter-system crossing (RISC) rates are estimated in a novel non-adiabatic approach that accounts for the anharmonicity of the torsional mode.
The dynamical response of the medium is considered with great care. Orientational relaxation in liquid solvents is fast (picoseconds) and the solvent is always in equilibrium with the dye. In organic matrices, most, but not all, orientational relaxation pathways are hindered, giving rise
to an intricate environment dynamics and static disorder. The model addresses both regimes allowing for the estimate of photophysical rates and the simulation of time resolved emission spectra.2023-01-01T00:00:00ZBioinorganic strategies for the development of metal-enzymes inhibitors and compounds with antitumor activityMiglioli, Francescahttps://hdl.handle.net/1889/54012023-06-22T14:21:32Z2023-01-01T00:00:00ZTitle: Bioinorganic strategies for the development of metal-enzymes inhibitors and compounds with antitumor activity
Authors: Miglioli, Francesca
Abstract: This PhD thesis is centred on two main research areas within the bioinorganic strategies for the development of bioactive compounds.
The first one regards the synthesis and characterization of water-soluble thiosemicarbazones (TSCs) copper complexes as compounds with anticancer activity. Promising results were previously obtained in this research group with salicylaldehyde TSCs Cu(II) complexes that, nevertheless, showed that their application could be improved enhancing their water solubility. Therefore, the first project focused on the synthesis of some sulfonated salicylaldehyde TSC ligands and of their copper(II) complexes. The synthesis of structurally modified ligands and complexes was carried out to have insights on the structure-activity relationship in this class of compounds. Another way to improve solubility brought to the synthesis of a panel of glyco-conjugate TSCs ligands and their copper(II) complexes.
The second subject concerns the synthesis and characterization of chelating compounds as inhibitors of viral metal-dependent enzymes, by using the validated strategy of the metal chelation of the ion cofactors within the active site of the target enzymes. The synthesis of different chelating compounds targeting the metal-dependent RNA-dependent RNA polymerase in viruses of the Bunyavirales order was undertaken. Several bunyaviruses represent emerging zoonotic pathogens and the therapeutic options for the treatment of these infections are very limited, thus the identification of effective antiviral compounds is of vital importance. Finally, due to the arrival of the COVID-19 pandemic, an in-house library of chelating compounds and metal complexes has been completed to be used in a screening targeting PLpro, a specific zinc-dependent enzyme of SARS-COV-2.2023-01-01T00:00:00Z