Applications of dissipative dynamic covalent chemistry based on transimination reactions

This thesis addresses the development and applications of a new branch of combinatorial chemistry: the dissipative dynamic covalent chemistry of imines. This approach combines the traditional dynamic combinatorial strategy, where a templating agent promotes the selective amplification of one or more members within a mixture of interconverting imines (a dynamic library of imines), with temporal control. As a result, the amplification of one or more specific members can be achieved for a limited and tunable period of time, after which the system spontaneously returns to its initial equilibrium composition. Chapter 1 explains how this transient change of composition can be achieved by involving the activated carboxylic acids (ACAs), a class of acids with dual functions. In fact, anACA can alter the properties of acid–base sensitive systems through a proton transfer reaction. Additionally, after a definite amount of time, its conjugate form undergoes a decarboxylation reaction to generate in situ a strong base, which takes back the previously transferred proton, counteracting the initial effect. In dynamic libraries of imines, these ACAs displace the equilibrium, initially in favour of N-aliphatic imines, toward the N-aromatic ones. The decarboxylation reaction reverts the starting N-aliphatic imines, and by tuning the rate of this process with the amount of ACA, temperature or solvent nature, it is possible to control the lifetime of the overexpressed N-aromatic imines. In Chapter 2 this strategy based on the transient amplification of N-aromatic imines will be extended from small molecules to supramolecular imine-based polymers, a class of macromolecules notable for their stimuli-responsive behaviour. Two different types of imine-based feedstocks were employed for this purpose: a monomeric macrocycle and a mixture of oligomers derived from covalent poly(imine). These two starting materials have in common their double imine functionality. The transimination reaction, triggered by an ACA, leads to divalent N-aromatic imines connected each other through supramolecular forces, resulting in a linear supramolecular assembly. ACA decarboxylation was responsible for the disassembly of these larger structures, restoring the starting feedstocks. Chapter 3 sets aside the dissipative chemistry of imines to focus on the development of a novel ACA containing two carboxylic and decarboxylative moieties (an A2 system, with A indicating each acid function). This acid was reacted with a bivalent aliphatic amine (a B2 system, with B indicating each basic function) to generate, in its conjugate form, a transient supramolecular ionic polymer due to attractive ionic interactions. These interactions were responsible for the ionic supramolecular copolymerization [A2–B2]n, before decarboxylation did not start. For this system, ionic interactions reinforced by hydrogen bonding were involved for promoting the formation of an assembly and, at the same time, some drawbacks that can affect imine-based polymers were neglected. This system was more likely to undergo linear polymeric assemblies than the imine-based species studied in Chapter 2 and, additionally, resulted in larger supramolecular polymers. In Chapter 4 the dissipative dynamic covalent chemistry of imines is extended to the colloidal phase, specifically on the surface of gold nanoparticles. In this project we started from long difunctional N- aliphatic imines free in solution, and the ACA addition transiently overexpressed N-aromatic di- imines. For this system, the amplified N-aromatic imines were responsible for the covalent bridging of different nanoparticles, enabling the reversible formation of a covalent network. In fact, ACA decarboxylation led to the covalent disassembly of the nanoparticles. This novel approach allowed the temporal control over the aggregation state of nanoparticles, an important tool for the future realization of sensors, catalysts or drug delivery systems.