Anna Lielpetere

Although organic electrosynthesis is regarded as an inherently green approach, its sustainability must be demonstrated beyond the mere use of electricity as a reagent, requiring the integration of broader principles, such as catalyst recovery and reuse. An underexplored approach is the use of polymer‐supported redox mediators or redox polymers, which can be either immobilized on the electrode surface or recovered and recycled. This review surveys the current literature on the application of organic redox polymers in organic electrosynthesis, covering redox polymer design, physicochemical characteristics, integration into electrochemical systems, and reaction methodology. Three established architectures of redox polymer application are compared: electrodes modified with ex situ synthesized or electropolymerized films, soluble redox polymers, and dispersed redox polymer systems. Existing literature examples demonstrate that redox polymer‐based methods can provide excellent yields and enantioselectivities, alter chemoselectivity, and enable transformations that are difficult to achieve with small‐molecule mediators. Nevertheless, the current scope of reactions, mediators, and polymer varieties remains narrow. Given the largely unrealized design space for these materials, redox polymers represent a significant opportunity for the development of sustainable electroorganic methodologies.

N-Alloc-protected furfuryl amino alcohols derived from furfural and ʟ- or ᴅ-valinol were subjected to Torii-type ester electrosynthesis to obtain the corresponding unsaturated esters. These served as key intermediates to prepare (S)- and (R)-enantioenriched unsaturated amides by N-Alloc deprotection which induced concomitant methoxymethyl group cleavage, O-to-N rearrangement, and isomerization of the double bond. An oxazoline ring formation in the resulting unsaturated amides provided the corresponding enantioenriched vinyloxazoline. The reactivity of the electron-deficient double bond in the vinyloxazoline was explored in several reactions. Out of these, the aza-Diels–Alder reaction with TsNCO was successful, leading to a highly diastereoselective formation of an oxazolo[3,2-c]pyrimidine derivative.

N-Alloc protected furfuryl amino alcohols derived from furfural and L- or D-valinol were subjected to Torii-type ester electrosynthesis to obtain the corresponding unsaturated esters. These served as key intermediates to prepare enantioenriched (S)- and (R)- unsaturated amides by N-Alloc deprotection which induced concomitant methoxymethyl group cleavage, O- to N- rearrangement, and isomerization of the double bond. An oxazoline ring formation in the resulting unsaturated amides provided the corresponding enantioenriched vinyl oxazolines. The reactivity of the electron deficient double bond in the vinyl oxazoline was explored in several reactions. Out of these, aza-Diels-Alder with TsNCO was successful, leading to a highly diastereoselective formation of oxazolo[3,2-c]pyrimidine derivative.

Wir schlagen eine hybride elektrokatalytisch‐bioelektrokatalytische Reaktionskaskade vor, die auf einer Gasdiffusionselektrode zur CO₂‐Reduktion unter selektiver Bildung von Methanol integriert ist. Ag‐Bi₂O₃ reduziert gasförmiges CO₂ bei neutralem pH‐Wert selektiv zu Formiat. Eine nachfolgende enzymatische Kaskade aus Formaldehyd‐Dehydrogenase und Alkohol‐Dehydrogenase, die beide von Nikotinamid‐Adenin‐Dinukleotid (NADH) abhängig sind, reduziert Formiat weiter sequentiell zu Formaldehyd und Methanol. Der enzymatisch oxidierte Redoxkofaktor NAD⁺ wird durch das Enzym Diaphorase regeneriert, das elektrochemisch an die Elektrode gekoppelt ist, indem es in ein Redoxpolymer auf Cobaltocen‐Basis eingebettet ist. Die Methanolbildung wird mithilfe eines hochselektiven Biosensors nachgewiesen, der auf Alkoholoxidase in Kombination mit Meerrettichperoxidase basiert, die in ein speziell angepasstes Redoxpolymer integriert sind. Die vorgeschlagene hybride elektrokatalytisch‐bioelektrokatalytische Kaskade ist ein Beispiel für eine allgemeine Strategie zur Verbesserung der Selektivität elektrokatalytischer Reaktionen und/oder zum Ersatz bioelektrochemisch anspruchsvoller Schritte wie der Synthese von Formiat aus CO₂ unter Verwendung sauerstoffempfindlicher Formiatdehydrogenasen durch robustere anorganische Elektrokatalysatoren.

We propose a hybrid electrocatalytic‐bioelectrocatalytic reaction cascade integrated on a gas diffusion electrode for CO₂ reduction under selective formation of methanol. Ag‐Bi₂O₃ selectively reduces gaseous CO₂ to formate at neutral pH conditions. A subsequent enzymatic cascade comprising formaldehyde dehydrogenase and alcohol dehydrogenase, which are both nicotinamide adenine dinucleotide (NAD)‐dependent, further reduce formate sequentially to formaldehyde and methanol. The enzymatically oxidized redox cofactor NAD⁺ is regenerated through the enzyme diaphorase which is electrochemically coupled to the electrode by embedding it into a cobaltocene‐based low‐potential redox polymer. Methanol formation is confirmed using a highly selective biosensor based on alcohol oxidase in combination with horseradish peroxidase integrated into a specifically adapted redox polymer. The proposed hybrid electrocatalytic‐bioelectrocatalytic cascade is an example for a general strategy for enhancing the selectivity of electrocatalytic reactions and/or to replace bioelectrochemically challenging steps such as the synthesis of formate from CO₂ using highly oxygen‐sensitive formate dehydrogenases by more robust inorganic electrocatalysts.

Research on implantable glucose biosensors is driven by the need for innovative medical devices for continuous glucose monitoring in patients with diabetes mellitus. However, biosensor sterilization is a step that is widely omitted during the process of innovation. To compare the effects of gamma irradiation and chemical treatment with ethylene oxide (carbon microarray electrodes are fabricated, functionalized with glucose oxidizing enzymes (cellobiose dehydrogenase CDH or glucose oxidase GOx), and coated with a specifically designed zwitterionic polymer prior to the sterilization step. Cyclic voltammetry in the presence of 100 mm glucose of the biosensors before and after sterilization shows that gamma irradiation with a low radiation rate (25 kGy, 260 Gy h⁻¹) does not induce a sensor performance loss, unlike the EtO treatment. In addition, no cytotoxic by‐products are released after gamma sterilization. Based on these results obtained with both glucose oxidizing enzymes (CDH and GOx), gamma irradiation of the glucose biosensors with a low dose rate is preferable to exposure to EtO for biosensor terminal sterilization.

Foreign body response is the main reason for the limited lifetime of implantable glucose biosensors. A new measurement strategy exerting minimal disturbance from the equilibrium glucose concentration in the sensor compartment has been proposed to mitigate its adverse effects on the sensor signal. Here, a new measurement strategy using automatically fabricated and robust pencil‐lead‐based glucose biosensors is implemented. The sensor response depends on critical parameters such as redox‐polymer film thickness, film uniformity, rigidity, polymer composition, and the ratio between the enzyme and the polymer. These parameters are controlled by introducing a short‐chain redox polymer, a low crosslinker amount, a short‐chain electrografting agent and linker, pulse electrografting, and an automated fabrication procedure.

In the last decade, synthetic organic electrochemistry has received renewed interest due to technological advances and its contribution to sustainable chemistry. In the Thesis, operationally simple electrochemical methods for new bond formation via carbenium ion generation have been developed. The research includes the use of electroauxiliary groups for the generation of carbenium ions and the electrochemical functionalisation of biomass-derived furan derivatives. The Thesis is a collection of thematically related scientific publications on developing new electrochemical methods for carbenium ion generation and use in reactions.