Estudo da viabilidade de complexação de piperidinas densamente funcionalizadas e xanteno com ciclodextrina

Abstract

The multicomponent synthesis process is a highly efficient methodology for constructing molecules with varied structures and diverse biological applications. It also adheres to the principles of green chemistry, as it reduces waste generation since the reaction is performed in a single step. The greatest chemical inspiration for the design of bioactive molecules comes from nature; piperidine and xanthene scaffolds are chemical structures inspired by plant secondary metabolites. These chemical structures exhibit a wide spectrum of biological activities, including anticancer, antiviral, antifungal, antidiabetic, and insecticidal properties, among others. In a distinct field, cyclodextrins stand out. These are cyclic oligosaccharides formed by glucose monomers linked by α-1,4 glycosidic bonds. The formation of inclusion complexes occurs through the encapsulation of apolar molecules (like hydrophobic bioactive) within the structural apolar cavity, establishing weak intermolecular interactions as London forces. The polar and hydrophilic CD exterior allows the interaction of molcules with the aqueous medium. This enables the solubilization of previously insoluble bioactives, such as functionalized piperidines and xanthenes. Furthermore, complexation offers chemical protection to the bioactive against external factors like pH and temperature, ensuring the structural integrity of the compound. The objective of this work was to study the feasibility of forming inclusion complexes between β-cyclodextrin and two different organic molecules classes: piperidines and xanthenes. Combining these strategies, it was observed that the complex formation with xanthenes was satisfactory, promoting the integrity of the molecule with an established ideal stoichiometry of 1:1 effectively. However, satisfactory results were not observed for the piperidines. Two hypotheses were raised: either the molecule's low intrinsic solubility interferes with the chemical equilibrium between the complexed and free forms, hindering the visualization of the solubilization effects provided by the cyclodextrin, or the β-cyclodextrin's small cavity may not properly accommodate the molecule, opening ways for new explorations. Thus, the formation of inclusion complexes is seen as a viable approach for the future application of these organic molecules, enabling the development of more efficient therapeutic systems with improved pharmaceutical performance and broader applicability of these structures. Keywords: inclusion complexes; densely functionalized piperidines; xanthenes; multicomponent synthesis; bioactives; cyclodextrin.