Development of materials with increasing structural complexity: from chiral stationary phases to covalent organic polymers and metal-organic frameworks

The engineering of artificial functional materials is one of the most dynamic scientific fields of the contemporary era. It is considered a multidisciplinary area that combines chemistry, physics, materials and computational science to design and synthesize new materials with properties optimized for specific assets and function. One of the first materials to be discovered was zeolites in the mid-1700s. Zeolites are microporous, generally crystalline minerals composed mainly of aluminosilicates of alkali or alkaline earth metals, such as sodium, potassium or calcium. They are characterized by a regular three-dimensional composed of silica (SiO₄) and alumina (AlO₄), which form cavities and channels at the molecular level. This class of microporous silicates is mainly used in catalysis, adsorption-separation, and ion exchange. The final structure of zeolites is highly unpredictable since it depends on several variables, such as the synthesis solvents, the direction agents in the structure, and the mineralizers. The true revolution in materials occurred in the 20th century with the advent of polymers, including groundbreaking like plastics and nylon. The 21st century has seen growing attention to nanometric-sized materials, such as carbon nanotubes, graphene and nanoparticles. These materials have unique physical and chemical properties, such as greater mechanical resistance and superior electrical conductivity. Graphene is a two-dimensional material composed of a single layer of carbon atoms arranged in a honeycomb (hexagonal) structure. Among its various properties, high electrical and thermal conductivity, mechanical resistance and flexibility stand out. It is a material used mainly in electrochemistry, for example, for the construction of supercapacitors and batteries. Another category of nanomaterials includes by carbon nanotubes (CNTs), which are cylindrical structures composed of one or more layers of graphene rolled into a tubular shape. They can be classified into single-walled carbon nanotubes (SWNTs) and multi-walled carbon nanotubes (MWNTs), depending on the number of graphene layers present. These exhibit properties and applications like graphene. Nanomaterials are also crucial for applications as separation phases, where their porosity plays a key role in enhancing performance and efficiency. Starting from separation techniques, the most widespread one is liquid chromatography, which involves the use of a solid stationary phase. The principal material used as the solid support for synthesizing stationary phases is silica, which consists of particles exhibiting permanent mesoporosity. The silica surface is covered with silanol groups (Si–OH) which are responsible for polar interactions and can act as acidic active sites. The silica surface can be chemically modified through derivatization processes to introduce various functionalities, thus broadening its applications. A classic example is silica modified with alkyl chains, such as C18 silica (octadecylsilane), widely used in reversed-phase chromatography (RP-HPLC). Moreover, silica can be efficiently derivatized with a wide array of specifically designed chiral molecules for separating enantiomers. Based on these modifications, the characteristics of chiral stationary phases are determined by the presence of chiral selectors and can be predicted with reasonable accuracy. Many stationary phases are currently available commercially, with one of the most notable being Pirkle's Whelk-O1, composed of silica derivatized with (1-(3,5-dinitrobenzamide)-1,2,3,4-tetrahydrophenanthrene). This stationary phase has proven to be one of the most commercially promising, as it can resolve various enantiomers under different experimental conditions. In recent years, research has focused on the study of covalent organic materials, which represent a very broad class that includes Covalent Organic Polymers (or COP), materials whose complexity varies depending on the precursors and can also present porous or non-porous structures. Their complexity relies on various factors, one above all the synthetic approach. The kinetic aspect of bond formation plays a crucial role in determining the material's structural organization. A higher rate of bond formation tends to increase the likelihood of irregularities or defects in the atomic arrangement, thereby promoting the formation of an amorphous structure. This is because rapid kinetics limit the time available for atoms to arrange into an ordered, crystalline structure, resulting in a disordered or amorphous state. For this reason, compounds that act as reaction modulators are frequently and voluntarily used in their synthesis. These materials are used primarily in the field of metal-heterogeneous organic catalysis; this is due to their insoluble nature in common organic solvents, their strong affinity for metals that allows them to be used as reaction catalysts, but above all, to be quickly recovered from the reaction environment and reused, thus advancing the entire process towards a more sustainable chemistry. The frameworks materials can be classified in Covalent Organic Frameworks (COFs) and Metal Organic Frameworks (MOFs). MOFs and COFs are crystalline porous materials, and they can be readily self-assembled from different molecular building pieces that interact with one another through covalent bonds or coordinated interactions. They have high porosity and large surface area that led to a wide range of applications. The main difference between MOFs and COFs lies in the constituents: in the first case there is an organic molecule that acts as a linker and a metal ion that act as nodes. These elements establish coordination interactions between them; in the second case, at least two organic molecules are present in the structure that establish covalent bonds, giving greater stability to the entire system compared to MOFs. Both materials can serve as carriers, due to their porosity, making them for electrochemical applications, purification, chromatographic separation, as well as catalysis, storage and gas adsorption. Although there are numerous synthetic methods to obtain these materials, current research focuses on developing approaches to reduce the environmental impact of often harmful organic solvents. However, the use of aqueous solvents as an alternative is often limited due to the poor insolubility of the organic precursors in water. This thesis presents the development of various materials described in three parts, each reflecting progressive increase in structural complexity. In the first part, the synthesis of two chiral selectors is described, their structure was designed starting from the commercially available Whelk-O1 selector. A preliminary study on their chiral discrimination capabilities was conducted by NMR, using one of selector as chiral solvating agent (CSA) towards ibuprofen. Once synthesized and characterized, the chiral selectors were anchored on silica. The CSPs obtained were packed in chromatographic columns tested on different racemic mixtures in specific experimental conditions. Finally, based on the obtained chromatographic data, molecular docking studies were conducted in presence of the best resolved racemate to analyse the significant interactions between the selectors and the selectands. Therefore, in this first part of the thesis we focused on preparation of a material that does not present a high intrinsic structural complexity, but this is only due to the structure of the anchored selector, which determines its properties. In the second part of the thesis a Covalent Organic Polymer (COP) based on amide bonds is presented. This is a material that is structurally more complex than the case of the CSP presented in the first part. This has been characterized from a chemical-morphological point of view and its amorphous and non-porous structure has been revealed. As mentioned above, a fundamental aspect to consider in the synthesis of covalent organic materials is the kinetics of bond formation; in this case, the amide bond formation occurs so quickly that it does not allow an ordered and crystalline structure. Due to the potential good coordination capacity, the prepared COPs were modified with different metals including copper and the resulting doped COPs have been tested. Initially, Cu2+@COP was obtained, which was reduced in the presence of ascorbic acid, obtaining Cu+@COP. In both cases, a chemical-morphological characterization was carried out, in addition to a careful analysis of the oxidation state of copper to confirm the reduction of the metal. The metal-organic supports obtained were used as potential catalysts in the CuAAC “click” reaction. After optimization of reaction conditions, product yields of Cu+@COP were compared with those obtained in homogeneous phase conditions, by using copper sulphate, and in addition, with those in heterogeneous phase but in presence of Cu2+@COP and ascorbic acid, as a reducing agent. As for all heterogeneous solid catalysts, Cu+@COP is removed by simple filtration, while the final product is purified through a crystallization process. Although it has not reached the optimal characteristics of crystallinity, surface area and porosity, this material has shown promising results as heterogeneous catalyst working in water media. In the third part of this thesis, a micellar approach has been employed to synthesize nanoscale porous crystalline materials, as previously documented in literature, resulting in MOFs with potential applications in supercapacitors and drug delivery. In short, the micellar approach employs two surfactants, SDS and CTAB, that form a micellar medium within which the MOFs grow. In particular, copper and manganese-based MOF nanoparticles (Cu-CAT-1 and Mn-BTC respectively) were synthesized and were chemically and morphologically characterized. Data obtained were compared with those reported in the literature using conventional synthetic methods. Morphological analysis demonstrates that nanoparticles were produced through the micellar approach, whereas conventional methods yielded fibrous structures serval micrometres in length. Given the well-established conductivity properties of Cu-CAT-1, these materials are currently being investigated for supercapacitor applications due to their favourable electrochemical characteristics and their enhanced processability due to their nanoscale dimension. If results will be promising, they will be used for the construction of asymmetric supercapacitors. The same approach has been used and optimized for synthesising iron-based MOFs (MIL-53 (Fe) and MIL-100 (Fe) respectively) at the nanometric scale. Also in this case, materials were fully characterized and results compared with those reported in the literature. Furthermore, a synthetic protocol has been developed and optimized to dope these systems with a biocompatible metal ion, magnesium. We have generated two MOF systems, i.e. magnesium-doped MIL-100 (Fe) and magnesium-doped MIL-53 (Fe)). Looking to the applicability, MIL-100 (Fe) and MIL-53 (Fe) are already known in the literature to have good properties as drug-carriers due to their excellent structural properties and low toxicity. This project aims to evaluate the potential toxicity and biocompatibility of these materials when shaped into nanoparticles at the nanoscale. Special attention will be given to magnesium doped systems, focusing on how the presence of magnesium influences these properties. In this case, synthesizing MOFs in nanoparticles form offers a significant advantage for in vivo applications, as these materials can more easily penetrate cells. On the contrary, conventional approaches, often produce microsized MOF crystals with polyhedral shapes, limiting their in vivo applicability. In this last part, we can highlight how, compared to the previous sections, prepared materials show a greater intrinsic structural complexity together with high crystallinity, porosity and surface area.