Advances in Electrochemical Approaches for CO2 Fixation in Organic Synthesis and O2 Reduction in Bioelectronics

This doctoral thesis covers diverse research efforts aimed at understanding of chemical reactivity and developing innovations regarding electrochemical processes in the field of organic chemistry and material sciences. In summary, during my PhD studies, I explored electrochemical methods for efficient organic synthesis and, to a lesser extent, for applications in bioelectronics. Additionally, I leveraged DFT calculations as mechanistic tools to explain and support reactivity insights. In Chapter II, linear free-energy correlations were established between carbanion basicity (pKaH), Gibb's free energy (DG0) and activation free energy (DG‡) of the carboxylation reaction and key reactivity descriptors were identified. As calculated or experimental pKaH values are easily available, the constructed correlation between pKaH and DG‡ is useful as a predictive tool to pave the way for designing novel CO2 fixation reactions. The Leffler-Hammond coefficient (a = 0.26±0.02) and the intrinsic kinetic barrier (DG0⧧ = 12.7±0.3 kcal∙mol-1) were determined as the slope and the intercept of the DG⧧ vs. DG⁰ plot. The two values align with recent scientific findings for the decarboxylation reaction (reverse reaction) and depict the carboxylation step as characterised by low intrinsic activation energy barriers and a modest dependence on DG0. Moreover, the discovered CO2 electrophilicity value (E) of −15.3 ÷ −18.7 underscore CO2 as a strong electrophile. Finally, the pivotal role of the CO2 distortion during the carboxylation step was investigated by the distortion/interaction analyses and the energetic-structural relationships. A predictive framework provides valuable insights for designing new processes, helping to minimise undesirable pathways by identifying the critical features that needs to be optimised in the reaction conditions. In Chapter III, the electrochemical carboxylation of dienones and extended-unsaturated carboxyl derivatives was described, leading to the synthesis of 6-oxocarboxylic acids and 1,6-dicarboxyl derivatives in modest yields (up to 57%). This unprecedent example of vinylogous reactivity involving CO2 and extended conjugated carbonyl systems – with the observed regioselectivity favouring d-carboxylation over b-carboxylation – display the umpolung reactivity enabled by cathodic conditions. The proposed reaction mechanism identifies dianions as the key intermediates in CO2 activation. The mechanistic insights include the DFT calculations of DG⧧ and DG0 values for the carboxylation step, considering different possible reaction pathways and offering a deeper understanding of the possible factors driving the process. PEDOT-based coatings are established materials for H2O2 generation, presenting exciting opportunities for further applications in bioelectronics, particularly in the electrochemical cancer-cell treatments. In Chapter IV, a protocol for the fabrication of PEDOT:PSS-coated acupuncture needles was developed and evaluated for H2O2 generation. PEDOT:PSS-based coatings on stainless steel, gold, and titanium metal substrates demonstrated their capability for cathodic applications to produce H2O2 via oxygen reduction reaction (ORR) with comparable yields (100 ÷ 130 uM) and faradaic efficiencies (21.9 ÷ 26.9%FY). The optimised protocols, emphasise the importance of surface modifications with PEDOT:PSS in enhancing the H2O2 production performance. While the coatings exhibited stability under cathodic conditions, delamination during anodic cycling were noted, underscoring the need for further refining developments. Ongoing research is focusing on studying the coating integrity and the coating-substrate interactions, alongside evaluating the fabricated needles for potential in vivo applications.