Calixarene-based langmuir monolayers : from crystallization templates to metal organic networks

Molecular self-assembly plays a pivotal role in biological processes and living organisms can be considered as the result of the self-assembly of discrete molecular building blocks into sophisticated functional structures. Biology provides countless examples of complex and functional hierarchical self-assembled structures ranging from protein and nucleic acid biosynthesis to biological membranes self-assembly. Although Nature may produce such structures with an extreme efficieny, man-made chemical strategies to produce large covalent architectures are typically more complex and tedious. Due to the difficulty to precisely control the formation of large macromolecular architecture through covalent synthetic strategies, the self-assembly approach has been extensively exploited for the creation of supramolecular entities.
Amphiphiles are compounds able to self-assemble in myriad supramolecular structures such as micelles, vesicles, nanosheets, nanorods, nanotubes and nanofibers, to name but a few. The shape of the resulting supramolecular assembly is dependent on the structure of the amphiphilic building block and type of solvent. Among all kinds of natural and synthetic amphiphiles, macrocyclic amphiphiles are of particular interest due to the possibility to conveniently control the hydrophilic/lipophilic balance of the final amphiphilic structure. The basket-like rigid conformation of calix[4]arenes, and the possibility to selectively functionalize both the upper and lower rim, make these molecules attractive building blocks for the design of amphiphilic compounds.
Amphiphilic calix[4]arenes that are essentially insoluble in water self-assemble as monomolecular films at the air-water interface, forming Langmuir monolayers, where the aliphatic chains point into air while the polar functions are immerged into the subphase. Langmuir monolayers of amphiphilic calix[4]arene derivatives have been demonstrated to interact with a wide range of solutes, ranging from ions to macromolecules. In addition to this, calix[4]arene-based monolayers have been shown to induce the interfacial crystallization of inorganic and organic solids. The polar heads of the macrocycles act as recognition units for the interfacial nucleation of the to-be-crystallized molecules. Electrostatic interactions, along with geometrical complementarity between the macrocycles polar functions and the solute are the determining factors for the interfacial crystal growth. In this thesis, the ability of Langmuir monolayers of a p-carboxycalix[4]arene derivative to act as templates for the crystallization of gabapentin (GBP), an active pharmaceutical ingredient used to relieve neuropathic pain, with a control over its polymorphism is reported.
The suitable chemical modification of the upper and lower rim of calix[4]arenes allows producing stable amphiphilic macrocycles able to form stable Langmuir monolayers at the air-water interface with strong affinities towards ions. The affinity of calix[4]arene-based Langmuir monolayers towards ions is mainly owing to the presence of a cavity that allows for the encapsulation of the ions, coupled with multiple polar ligating functions at the p-positions that strongly interact with the solute. In this thesis, the recognition properties of Langmuir monolayers of a series of p-carboxy- and p-aminocalix[4]arene derivatives towards strong, i.e. CuCl2, CoCl2, NiCl2 and MnCl2, and weak, i.e. HgCl2, electrolytes are reported. The effect of the inorganic compounds on the self-assembly properties of the calix[4]arene-based Langmuir monolayers is investigated by means of surface pressure-area compression isotherms, Brewster angle microscopy (BAM) and synchrotron-based X-ray diffraction techniques. Notably, it has been demonstrated that the structure of the macrocycle has a crucial effect on its interfacial organization. Upon interaction of a long chain, i.e. C12, p-carboxycalix[4]arene derivative with Cu2+ ions at the air-water interface, the corresponding calix[4]arene-based monolayer is mainly amorphous. On the other hand, Langmuir monolayers of the short chain (C3), structural analogue on aqueous Cu2+ ions subphases possess significantly large and highly ordered structures. It is assumed that the interfacial self-assembly of the long chain p-carboxycalix[4]arene derivative is mainly driven by van der Waals interactions among the aliphatic chains, which contribute to the partial disordered monolayer structure. On the contrary, the self-assembly of the short chain p-carboxycalix[4]arene derivative is driven by π-π interactions among aromatic rings of neighboring amphiphiles, which contribute to the highly ordered structure of the monomolecular film.