Stimuli-responsive Pyridiniumbased Macrocyclic Hosts

Abstract

This doctoral thesis presents the development and study of stimuli-responsive macrocyclic receptors based on pyridinium salts. As a common nexus, these molecular systems are obtained under thermodynamic control, making use of metal-directed self-assembly and imine bonding, which facilitates obtaining (supra)molecules with high yields in self-repairing processes. Moreover, all of these macrocyclic systems are designed to present common structural characteristics, owning in consequence hydrophobic cavities with π-deficient regions prone to recognize complementary organic molecules in water. First, it will be shown the preparation in water of a dynamic combinatorial library of six different metallacycles through Pt-directed self-assembly of a flexible ditopic ligand based on a N-monoalkyl-4,4'-bipyridinium scaffold. This metallacyclic library can be manipulated by intrinsic factors, according to Le Chatelier’s principle, such as the concentration of building blocks, temperature or addition of a suitable aromatic substrate as chemical effector, resulting in the expression of one of the supramolecules, the one capable of optimization of host-guest interactions. . On the other hand, it will be presented here the synthesis of a new pH-responsive polycationic molecular receptor ("white box") based on the well-known organic receptor cyclobis(paraquat-p-phenylene) ("blue box"). This macrocycle has been obtained in water on a preparative scale, from acyl hydrazone bonding between two complementary pyridine ligands. The compound is, as far as we know, the first reported examples of a polycationic cyclophane having an accessible acid/base responsiveness, which is promoted by the considerable abnormal acidity of amide hydrogens within its structure. It has also been observed that in acidic conditions this macrocycle has conformational isomerism, due to the free rotation around the amide bonds, which can be fixed at high pH values. This dynamism is translated into a molecular receptor capable of recognizing aromatic substrates in a lock and key or induced-fit fashion depending on the reaction conditions. Finally, the “red box” is presented as another iteration of our designed molecular receptors based on the previously cited “white box”. In this case, the synthesis has been carried out by replacing acyl hydrazone for hydrazone bond and, like its counterpart, has a remarkable pH dependence on its structure. In this case, a synthetic improvement has been observed, because of the synthetic process being carried out without the need for a template assistance, in a kinetically-controlled process that yields imine bonds with unusually high hydrolytic stability. While in aqueous media the "red box" is capable of complexing aromatic substrates both in its acidic and basic form, in organic media the corresponding host-guest systems behaves as a supramolecular switch, with the cyclophane being only capable of capturing organic substrates in its acidic form.