L'elettrochimica quale strumento fondamentale per accrescere la comprensione e l'implementazione della polimerizzazione radicalica per trasferimento di atomo - Electrochemistry as a crucial tool to broaden atom transfer radical polymerization understanding and implementation

Controlling processes by electrochemical means is increasingly attracting the attention of organic and polymer chemists. Electrochemistry provides tunable parameters without requiring the addition of external compounds, often increasing system tolerance to impurities, thus facilitating reaction handling and switching among different stages. In the last decades, the main interest in polymer chemistry concerned the preparation of predetermined macromolecular architectures. Atom transfer radical polymerization (ATRP) is the most powerful and versatile method to build well-defined polymers, with narrow molecular-weight distribution and excellent retention of chain-end functionalities. ATRP is based on the reversible deactivation of propagating radicals, such as to extend the lifetime of polymer chains. Radical concentration in solution is always very low, ultimately minimizing their probability of terminating. The activation-deactivation equilibrium is generally governed by a metal catalyst, composed by copper and a polydentate amine ligand. The active form of the catalyst, [CuIL]+, generates radicals by reductive cleavage of the C–X bond in the alkyl halide initiator, RX. As a consequence of the electron transfer and the concurrent atom transfer, the deactivator [X–CuIIL]+ is formed. Generated radicals add to few monomer molecules (i.e. propagation reaction), then they are reverted to their dormant state by reacting with [X–CuIIL]+. Importantly, RX initiators should be highly reactive, as to ensure the simultaneous growth of all polymer chains, thereby targeting pre-determined molecular weights. Chain-end functionalities are preserved during the polymerization, thus enabling several post-polymerization processes and the building of copolymers with various compositions and topologies. The aim of this thesis is to affirm electrochemical tools as a primary, effective and accessible source for ATRP triggering and mechanistic analysis. Less than 20 years ago, electrochemistry was involved for the first time in ATRP, when standard reduction potentials of some common catalysts were determined by cyclic voltammetry (CV) and correlated to their catalytic performances. Since then, CV is a well-established technique to study the redox properties of ATRP catalysts and the relative affinity of CuI and CuII species for halide ions, hence predicting their activity in the polymerization. Moreover, many electrochemical procedures were arranged for the precise measurement of the activation rate constant, kact, which concerns the reaction between [CuIL]+ and RX. kact values spanning over a range of 12 orders of magnitude were measured with different techniques, in many environments. Among these techniques, the use of a rotating disk electrode allowed a fast, easy and highly reproducible measurement. This instrument was further exploited in this thesis work to set up a facile electrochemical procedure for the determination of the thermodynamic equilibrium constant of ATRP, KATRP. Essentially, the reaction between CuI species and RX was followed as for kact determination, but in the absence of a radical scavenger that had been used to kinetically isolate the activation step. The interplay between activation, deactivation and radical termination was monitored, and KATRP was obtained by elaborating the electrochemical response through an equation proposed by Fischer and recently slightly modified. The method was applied to different Cu catalysts, initiators, solvent/monomer combinations and temperatures, observing some trends in accordance with general ATRP understanding. Both kact and KATRP must be measured in the absence of halide ions, which strongly affect the speciation of CuI. Indeed, the amount of active [CuIL]+ is reduced by the formation of various halogenated CuI species, thus slowing down the reaction with RX. However, the drop in the rate of CuI consumption in the presence of different C_(X^- ) was used to estimate the association constant of X− to [CuIL]+ (i.e. CuI halidophilicity constant, K_X^I). A procedure to measure K_X^I from K_ATRP^app, obtained under various C_(X^- ), was reported and verified for an independently determined K_X^I value. Electrochemistry is not only used to study ATRP mechanism, but also to effectively trigger the polymerization process. In fact, an applied current or potential is used to re-generate CuI from [X–CuIIL]+, which accumulates in solution because of termination events. Electrochemically mediated ATRP (eATRP) uses electrons as a reducing agent, thus it is free of by-products and allows to start from a minimum amount of air-stable CuII, which is reduced in situ. Nonetheless, the traditional eATRP setup required a potentiostat and expensive Platinum electrodes. During my Ph.D., I tried to simplify the setup as to make eATRP a cost-effective and scalable technique. Various inexpensive and easily functionalizable materials were successfully used as cathodes for eATRP in both organic and aqueous media. These working electrodes allowed well-controlled polymerizations even under galvanostatic conditions (i.e. constant current steps), which permitted the use of two, instead of three electrodes, and the replacement of the potentiostat with a common current generator. Furthermore, these cathodes were coupled to a sacrificial Aluminum anode in a completely Pt-free setup. Finally, these materials did not release metal ions in solution during the polymerization, and their morphology was not modified, thus they could be re-used in consecutive experiments. One important feature of eATRP and ATRP in general is their high versatility. Actually, various types of monomers are suitable for these techniques. Instead, controlled polymerization of acidic monomers via ATRP was considered impossible until very recently. In 2016, Fantin at al. proved that growing chains of poly(methacrylic acid) in ATRP were affected by a cyclization reaction with loss of C-X functionalities, i.e. termination. Suitable conditions to overcome this issue were proposed and successful eATRPs of methacrylic acid were reported. This important achievement was extended to acrylic acid (AA), which is a biocompatible, largely used monomer. In this thesis, it is proved that AA polymerization was hampered by the same cyclization side reaction during eATRP. Indeed, some conditions that were suitable for methacrylic acid were successfully adapted to eATRP of AA. i) Chloride ions replaced bromides, and ii) polymerization rate was enhanced by using a cathode with large surface area, applying a strongly negative potential, compared to Eѳ of the catalyst, and optimizing the amount and the nature of other reactants. One way to broaden the applicability of ATRP is to design new ligands able to convey particular features to Cu catalysts. Herein, 4 new ligands are presented, in which the skeleton of the traditionally used tris(2-methylpyridyl)amine (TPMA) was modified with m-functionalized phenyl substituents. Electrochemical characterizations of Cu complexes with these ligands allowed to predict a lower activity toward RX, compared to parent TPMA, which was proved by kact determination. Nevertheless, these complexes were used to catalyze well-controlled eATRPs of methyl methacrylate in DMF, and oligo (ethyleneoxide) methyl ether methacrylate and methacrylic acid in water. Despite the low activity, these compounds were very stable even at acidic pH and can be used to tune the polymerization in extremely reactive system. The versatility of ATRP is also reflected by the application in different environments. Ionic liquids for example are attracting great interest as green solvents for polymerizations. In 1-butyl-3-methylimidazolium trifluoromethanesulfonate, the redox properties of common ATRP catalysts and initiators were investigated by CV, whereas kinetic studies were performed via rotating disk electrode. This work proved that the behavior of Cu complexes and RX in ILs is similar to the one observed in traditional organic solvents. Therefore, ILs are suitable media for controlled polymerizations, and particularly they should be applied as solvent for eATRP because they are sufficiently conductive without added supporting electrolytes. Dispersed media represent another eco-friendly environment for polymerizations. Although many industrial processes are based on (mini)emulsion systems, the vast majority of literature reports on ATRP concerns experiments in homogeneous solutions. ATRP in miniemulsion required the design of super hydrophobic catalysts that remained confined into hydrophobic droplets, whereby tuning the polymerization. During my Ph.D., I spent six months as a visiting student at Carnegie Mellon University, in the laboratory of Prof. Matyjaszewski, who discovered ATRP in 1995. There, I had the opportunity to work on ATRP in miniemulsion and emulsion. A new catalytic system was arranged, and effectively applied to eATRP and activators re-generated by electron transfer (ARGET) ATRP, in which a reducing agent is added to continuously re-generate CuI species. Common hydrophilic catalysts were combined to inexpensive surfactants to form ion pairs able to enter the monomer droplets and catalyze the process. Electrochemical and spectrochemical characterizations proved the interactions between the compounds and defined the different contributions from ion-pair and interfacial catalysis. Block copolymers, polymer stars and brushes were easily synthetized with this approach. Moreover, residual copper in precipitated polymers was very low, even < 1 ppm, thus avoiding the need of further purifications. The system was then adapted to emulsion ARGET-ATRP, taking advantage of the water-solubility of the catalyst, which is a requirement of emulsion polymerizations, where the process should occur in the aqueous phase. By using suitable hydrophilic initiators and finely tuning the stirring rate and the pre-emulsification procedure, well controlled ab ini