Functional engineering of hybrid heterostructures for application in electronic, optical and optoelectronic nanostructured devices

Interfacing materials with different intrinsic chemical-physical characteristics allows for the generation of a new system with multifunctional features. Here, this original concept is implemented for tailoring the functional properties of bi-dimensional black phosphorus (2D bP or phosphorene) and organic light-emitting transistors (OLETs). Phosphorene is highly reactive under atmospheric conditions and its small-area/lab-scale deposition techniques have hampered the introduction of this material in real-world applications so far. The protection of 2D bP against the oxygen by means of functionalization with alkane molecules and pyrene derivatives, showed long-term stability with respect to the bare 2D bP by avoiding remarkable oxidation up to 6 months, paving the way towards ultra-sensitive oxygen chemo-sensors. A new approach of deposition-precipitation heterogeneous reaction was developed to decorate 2D bP with Au nanoparticles (NP)s, obtaining a “stabilizer-free” that may broaden the possible applications of the 2D bP/Au NPs interface in catalysis and biodiagnostics. Finally, 2D bP was deposited by electrospray technique, obtaining oxidized-phosphorous flakes as wide as hundreds of µm2 and providing for the first time a phosphorous-based bidimensional system responsive to electromechanical stimuli. The second part of the thesis focuses on the study of organic heterostructures in ambipolar OLET devices, intriguing optoelectronic devices that couple the micro-scaled light-emission with electrical switching. Initially, an ambipolar single-layer OLET based on a multifunctional organic semiconductor, is presented. The bias-depending light-emission shifted within the transistor channel, as expected in well-balanced ambipolar OLETs. However, the emitted optical power of the single layer-based device was unsatisfactory. To improve optoelectronic performance of the device, a multilayer organic architecture based on hole-transporting semiconductor, emissive donor-acceptor blend and electron-transporting semiconductor was optimized. We showed that the introduction of a suitable electron-injecting layer at the interface between the electron-transporting and light-emission layers may enable a ≈ 2× improvement of efficiency at reduced applied bias.

Strategies to hijack MTs dysfunction in neurodegenerative tauopathies: Design and synthesis of novel CNS-disease-modifying tools

Neuronal microtubules assembly and dynamics are regulated by several proteins including (MT)-associated protein tau, whose aberrant hyperphosphorylation promotes its dissociation from MTs and its abnormal deposition into neurofibrillary tangles, a common neurotoxic hallmarks of neurodegenerative tauopathies. To date, no disease-modifying drugs have been approved to combat CNS tau-related diseases. The multifactorial etiology of these conditions represents one of the major limits in the discovery of effective therapeutic options. In addition, tau protein functions are orchestrated by diverse post-translational modifications among which phosphorylation mediated by PKs plays a leading role. In this context, conventional single-target therapies are often inadequate in restoring perturbed networks and fraught with adverse side-effects. This thesis reports two distinct approaches to hijack MT defects in neurons. The first is focused on the rational design and synthesis of first-in-class triple inhibitors of GSK-3β, FYN, and DYRK1A, three close-related PKs, which act as master regulators of aberrant tau hyperphosphorylation. A merged multi-target pharmacophore strategy was applied to simultaneously modulate all three targets and achieve a disease-modifying effect. Optimization of ARN25068 by a computationally and crystallographic driven SAR exploration, allowed to rationalize the key structural modifications to maintain a balanced potency against all three targets and develop a new generation of quite well-balanced analogs exhibiting improved physicochemical properties, a good in vitro ADME profile, and promising cell-based anti-tau phosphorylation activity. In Part II, MT-stabilizing compounds have been developed to compensate MT defects in tau-related pathologies. Intensive chemical effort has been devoted to scaling up BL-0884, identified as a promising MT-normalizing TPD, which exhibited favorable ADME-PK, including brain penetration, oral bioavailability, and brain pharmacodynamic activity. A suitable functionalization of the exposed hydroxyl moiety of BL-0884 was carried out to generate corresponding esters and amides possessing a wide range of applications as prodrugs and active targeting for cancer chemotherapy.

Organic photosensitizers and nanostructured semiconductors for photoredox catalysis and artificial photosynthesis

Over the course of evolution, Nature has elegantly learned to use light to drive chemical reactions. On the other hand, humans have only recently started learning how to play with this powerful tool to carry out chemical transformations. In particular, a step forward was possible thanks to molecules and materials that can absorb light and trigger a series of processes that can drive chemical reactions. However, scarce elements are extensively employed in the design of most of these compounds and considerations on their scarcity and toxicity have sparked interest on alternatives based on earth-abundant elements. In this framework, the focus of this thesis has been the development and employment of heavy-metal free chromophores and of earth-abundant oxides. The first chapter regards the functionalization of boron-dipyrromethenes (BODIPYs) so as to allow access to their triplet excited state and tune their redox potentials, which was achieved thanks to the design of orthogonal donor-acceptor dyads. The BODIPY dyads were used to promote a photoredox reaction, and the mechanism of the reaction was clarified. In the second chapter, organic chromophores that display thermally-activated delayed fluorescence (TADF) were studied. These were used to perform enantioselective photoredox reactions, and a mechanistic investigation allowed to elucidate the fate of these photosensitizers in the reaction. Thanks to their stronger reducing power, it was possible to demonstrate the employability of TADF dyes in artificial photosynthesis, as well. Last, the oxidation of biomass-derived compounds was studied in a photoelectrochemical cell. For this purpose, hematite photoanodes were synthesized in collaboration with Prof. Caramori’s group at the University of Ferrara (Italy) and they were tested in the presence of a redox mediator. In addition to this, the possibility of repurposing a copper(II) water oxidation catalyst for the oxidation of biomass was investigated in collaboration with Prof. Llobet’s group at ICIQ (Tarragona, Spain).

Novel prototypes of electro-activated molecular machines

The work presented in this thesis deals with the investigation of new prototypes of molecular machines, based on rotaxane and pseudorotaxane architectures, by means of voltammetric and spectroscopic techniques. The discussion is divided in two parts. Part I concerns the investigation of electro-switchable molecular muscles, based on mechanically interlocked molecules. This study is performed on systems of increasing complexity, starting from [2]rotaxanes and arriving to polymers. In Chapters 3 and 4, [2]- and [3]rotaxanes, characterized by the presence of three stations for the macrocycle(s), are investigated. In both systems, the macrocycle(s) movement can be controlled through a combination of stimuli, resulting in a processive and directional motion. In Chapter 5, daisy chain rotaxanes, dimers of the [2]rotaxanes discussed in Chapter 3, are investigated. These systems can be switched between an extended and a contracted conformation, and they represent the monomeric units for the realization of polymeric molecular muscles. In Chapter 6, the properties of electro-switchable polymeric molecular muscles, composed by the daisy chains investigated in Chapter 5, are discussed. The repeating units of these poly-daisy chains contract and extend upon electrical stimulation, and this motion is expected to be transmitted to the polymer itself, resulting in an amplification of the effect. Part II concerns the investigation of rotaxanes and pseduorotaxanes based on heteroditopic calix[6]arenes and cationic guests. In Chapters 8 and 9, novel calix[6]arene macrocycles, functionalized with thiourea or dansyl units, and their related pseudorotaxanes are investigated. In both cases, the calix[6]arene functionalization adds new features to the pseudorotaxane. In Chapters 10 and 11, the influence of orientational isomerism on the properties of [2]- and [3]rotaxanes is investigated. The [3]rotaxanes discussed in Chapter 10 display similar properties, while the [2]rotaxanes described in Chapter 11, characterized by a calix[6]arene and a stilbazolium unit, exhibit distinct photophysical and photochemical properties.

Novel functionalized calcium phosphates: structures, morphologies and potential applications.

The stable increase in average life expectancy and the consecutive increase in the number of cases of bone related diseases has led to a growing interest in the development of materials that can promote bone repair and/or replacement. Among the best candidates are those materials that have a high similarity to bones, in terms of composition, structure, morphology and functionality. Biomineralized tissue, and thus also bones, have three main components: water, an organic matrix and an inorganic deposit. In vertebrates, the inorganic deposit consists of what is called biological apatite, which slightly differ from stoichiometric hydroxyapatite (HA) both in crystallographic terms and in the presence of foreign atoms and species. This justifies the great attention towards calcium phosphates, which show excellent biocompatibility and bioactivity. The performances of the material and the response of the biological tissue can be further improved through their functionalization with ions, biologically active molecules and nanostructures. This thesis focuses on several possible functionalizations of calcium phosphates, and their effects on chemical properties and biological performances. In particular, the functionalizing agents include several biologically relevant ions, such as Cobalt (Co), Manganese (Mn), Strontium (Sr) and Zinc (Zn); two organic molecules, a flavonoid (Quercetin) and a polyphenol (Curcumin); and nanoparticles, namely tungsten oxide (WO3) NPs. Functionalization was carried out on various calcium phosphates: dicalcium phosphate dihydrate (DCPD), dicalcium phosphate anhydrous (DCPA) and hydroxyapatite (HA). Two different strategies of functionalization were applied: direct synthesis and adsorption from solution. Finally, a chapter is devoted to a preliminary study on the development of cements based on some of the functionalized phosphates obtained.