Composites based on metal organic frameworks and plasmonic nanoparticles: synthesis, characterization and applications

Abstract

Metal-organic frameworks (MOFs) are a class of crystalline materials composed of inorganic units (e.g. atoms, clusters, planes) coordinated to organic polycomplexant ligands. MOFs offer several unique properties that make them attractive for a wide range of applications. First, they are known for their high and regular porosity with large surface areas and pore volumes. Also, their tunability allows customization to suit specific needs by selecting metal nodes and organic linkers. Their structural diversity can influence their physical and chemical properties; they can even afford therapeutic activity. MOFs can be designed with a variety of compositions and structures, including one-dimensional, two-dimensional, and three-dimensional frameworks. Since their discovery in the 1990s, MOFs have gained significant attention for their potential use in various fields, such as fluid storage and separation, catalysis, biomedicine, and environmental remediation, among others. MOFs represent a versatile platform in material science, enabling the development of advanced materials, even more so when combined with plasmonic nanoparticles (NPs). Indeed, plasmonic NP MOF composites are advanced materials that combine the unique properties of MOFs with NPs. These composites leverage the highly porous and tunable nature of MOFs alongside the enhanced optical properties of plasmonic NPs, such as gold or silver, which can generate localized surface plasmon resonance (LSPR). The combination allows for the design of materials with specific optical, chemical, and physical properties, tailored for diverse applications in both medical and environmental fields. The integration of plasmonic NPs into MOFs allows for efficient light absorption and conversion into heat, making a priori these composites highly effective for photothermal therapy (PTT), particularly in cancer treatment. Additionally, the porous nature of MOFs can be utilized for loading drugs, while the LSPR of the NPs can be used to trigger drug release at specific sites, enhancing the efficacy and precision of treatments. Continued research in this area promises further advancements in material science and practical applications. In particular relating to the following issues; - current antibacterial treatments are mainly antibiotics. They present a threat to the environment and their overuse has led to an increase in antibiotic resistant bacteria, - current antitumoral treatments present major adverse effects because of the uncontrolled biodistribution of the therapeutic agent, - the stability of materials for bio-applications constitutes a considerable hurdle to overcome, the materials need to be stable enough to reach the target and be shelfed, - current catalysts may present negative impact on the environment and the biosphere. In this sense, this PhD work specifically proposes: intrinsically active MOFs for antibacterial treatment (Chapter 3) as an alternative to antibiotics; plasmonic nanocomposite as targeted drug delivery systems (Chapter 4) for antitumoral treatment to minimize treatment drawbacks; the enhancement of the biostability of drug nanocarriers (Chapter 5) by surface functionalization; or the use of biosafe catalysts based on a NP/MOF composite (Chapter 6) for water remediation. In Chapter 3, two novel antimicrobial MOFs were developed based on active divalent metals (Zn, Cu) and ligand (poly(phenylene)vinylene derivative). The materials were obtained by solvothermal synthesis and fully characterized by a panel of solid-state techniques (e.g. X Ray Diffraction (XRD), Fourier transform InfraRed (FTIR) spectroscopy, UV-Vis spectroscopy, Scanning and Transmission Electron Microscopy (SEM, TEM), optical microscopy, Dynamic Light Scattering (DLS), Zeta Potential, Thermo Gravimetric Analysis (TGA), among others). The structures served as means of delivery of a combination of active pharmaceutic agents (APIs); ligand and cations, as an alternative to antibiotic treatment. Both Gram-positive and -negative bacteria were effectively tackled by the materials, reaching improved antibacterial effect when compared with the isolated components. As alternative to intrinsically therapeutic MOFs and with the aim to obtain combined antitumoral therapies, Chapter 4 addresses the formation of advanced nanocomposites based on photoactive inorganic NPs and MOFs. Using a two-step process, optically active Au/AgNPs were introduced to the photoactive microporous titanium(IV) terephthalate MIL-125-NH2. First, using a previously published technique, AgNPs were synthesized by photoreduction. Second, mixed metal Au/AgNPs were produced within the MIL-125-NH2 framework via green galvanic replacement synthesis, which exploited the potential difference between Au and Ag. The resulting homogeneous and small Au/AgNPs (3.5±0.9 nm) were evenly distributed throughout the MOF, as confirmed by high resolution transmission electron microscopy (HR-TEM). Additional characterization of the system was performed (e.g. XRD, DLS, N2 sorption, UV-Vis spectroscopy). The nanocomposite exhibited improved properties, such as an additional characteristic electronic band, increased stability in water and photothermal properties. Finally, the antitumoral doxorubicin was successfully encapsulated in these nanocomposites. To improve the materials' biostability and biosafety, the MOFs and composites' surface functionalization was investigated in Chapter 5. Not only the photoactive MIL-125-NH2 and its Au/AgNPs nanocomposite was selected for this aim, but also the microporous iron(III) aminoterephthalate MIL-88B-NH2, with an already proven biocompatibility and a flexible structure, able to reversibly adapt its pore size to the adsorbate (e.g. drugs), leading to a priori progressive release. In fact, AuNP composites were also synthesized and fully characterized in the flexible MIL-88B-NH2 (Chapter 6), using a straightforward impregnation and chemical reduction process, extremely repeatable and environmentally friendly. The pristine MIL-88B-NH2 and its AuNP composite showed particularly low stability in biological media, thus emphasizing the need for post synthetic modification in order to envision its potential implementation in biological applications. The surface functionalization was performed with heparin because it is highly available, cost efficient and has a reported shielding effect from the immunity system which leads to longer circulation of the nanocarriers in the blood stream. The materials were analyzed by XRD, TGA, DLS, and zeta potential and High-Performance Liquid Chromatography (HPLC performed to assess the degradation of the materials over time). The two MOFs are based on the same linker but different metals. The surface functionalization of the materials was effective with ~15wt.% of heparin in both materials, which suggests that the process may be implementable on all aminotherephthalate based MOFs. The findings demonstrated that the materials were comparatively biosafe and that MIL-88B-NH2 and AuNP/MIL-88B-NH2's bio-stability was significantly enhanced by surface functionalization with a decrease of up to 30% in degradation (or linker release). Conversely, in the MIL-125-NH2 based materials, the effect of the heparin is less pronounced with a decrease of 10% maximum in linker release namely because the materials are stable without it. Tests over longer periods of time may clarify the effect of heparin in the MIL-125-NH2. Finally, the AuNP/MIL-88B-NH2 nanocomposite was also evaluated as catalyst in the reduction of nitroarene (NO2 reduced to NH2). The latter pose significant health and environmental risks due to their toxicological properties (e.g. genotoxicity, carcinogenicity) and persistence in the environment. Nitroarenes are primarily released into the environment through industrial effluents, agricultural runoff, and urban waste. As such, the nitroarenes decontamination in water constitutes a means to protect the environment and preemptively fight adverse health effects. The nanocomposite was analyzed by different techniques (XRD, FTIR, UV-Vis….) and when it came to reducing harmful nitroarenes, it demonstrated excellent effectiveness and selectivity which was assessed by Gas Chromatography Mass Spectrometry (GC-MS). The materials reached up to >99% of conversion in 30 min, and showed high selectivity; other groups susceptible to reduction were not affected (such as ethoxyl or halogens). The composite was cycled five times and was still effective. Furthermore, the environmental impact of the catalytic process was analyzed using green metrics, showing an improvement compared to other catalysts. The syntheses discussed here address certain shortcomings of the current state of the art, namely towards the environmental impact and reproducibility. The synthesis presented in this thesis were performed while minimizing waste, the use of toxic reagents (in order to minimize the environmental impact of the materials) and the reproducibility which is far too often an issue with novel material synthesis Furthermore, the acquired composites were examined in various relevant applications (health and environment), demonstrating the potential of MOFs.