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1. Synthesis of redox-active fluorinated 5-hydroxytryptophans as molecular reporters for biological electron transfer

   https://doi.org/10.1039/d1cc00187f  

   Ohler, Amanda; Long, Hanna; Ohgo, Kei; Tyson, Kristin; Murray, David; Davis, Amanda; Whittington, Chris; Hvastkovs, Eli G.; Duffy, Liam; Haddy, Alice; et al (January 2021, Chemical Communications)

   null (Ed.)

   Fluorinated 5-hydroxytryptophans (F n -5HOWs) were synthesized in gram scale quantities and incorporated into a β-hairpin peptide and the protein azurin. The redox-active F n -5HOWs exhibit unique radical spectroscopic signatures that expand the function of 5HOW as probes for biological electron transfer. 

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2. The energetics and evolution of oxidoreductases in deep time

   https://doi.org/10.1002/prot.26563  

   McGuinness, Kenneth N.; Fehon, Nolan; Feehan, Ryan; Miller, Michelle; Mutter, Andrew C.; Rybak, Laryssa A.; Nam, Justin; AbuSalim, Jenna E.; Atkinson, Joshua T.; Heidari, Hirbod; et al (August 2023, Proteins: Structure, Function, and Bioinformatics)

   Abstract The core metabolic reactions of life drive electrons through a class of redox protein enzymes, the oxidoreductases. The energetics of electron flow is determined by the redox potentials of organic and inorganic cofactors as tuned by the protein environment. Understanding how protein structure affects oxidation–reduction energetics is crucial for studying metabolism, creating bioelectronic systems, and tracing the history of biological energy utilization on Earth. We constructed ProtReDox (https://protein-redox-potential.web.app), a manually curated database of experimentally determined redox potentials. With over 500 measurements, we can begin to identify how proteins modulate oxidation–reduction energetics across the tree of life. By mapping redox potentials onto networks of oxidoreductase fold evolution, we can infer the evolution of electron transfer energetics over deep time. ProtReDox is designed to include user‐contributed submissions with the intention of making it a valuable resource for researchers in this field. 

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3. Electrochemical Zero-Mode Waveguide Studies of Single Enzyme Reactions

   https://doi.org/10.1109/NANO.2018.8626402  

   Han, D.; Kwon, S.-R.; Fu, K.; Crouch, G.M.; Bohn, P.W. (July 2018, 2018 IEEE 18th International Conference on Nanotechnology (IEEE-NANO))

   null (Ed.)

   Because electron transfer reactions are fundamental to life processes, such as respiration, vision, and energy catabolism, it is critically important to understand the relationship between functional states of individual redox enzymes and the macroscopically observed phenotype, which results from averaging over all copies of the same enzyme. To address this problem, we have developed a new technology, based on a bifunctional nanoelectrochemical-nanophotonic architecture - the electrochemical zero mode waveguide (E-ZMW) - that can couple biological electron transfer reactions to luminescence, making it possible to observe single electron transfer events in redox enzymes. Here we describe E-ZMW architectures capable of supporting potential-controlled redox reactions with single copies of the oxidoreductase enzyme, glutathione reductase, GR, and extend these capabilities to electron transfer events where reactive oxygen species are synthesized within the  100 zL volume of the nanopore. 

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4. Polarizable embedding for simulating redox potentials of biomolecules

   https://doi.org/10.1039/c9cp01533g  

   Tazhigulov, Ruslan N.; Gurunathan, Pradeep Kumar; Kim, Yongbin; Slipchenko, Lyudmila V.; Bravaya, Ksenia B. (June 2019, Physical Chemistry Chemical Physics)

   Redox reactions play a key role in various biological processes, including photosynthesis and respiration. Quantitative and predictive computational characterization of redox events is therefore highly desirable for enriching our knowledge on mechanistic features of biological redox-active macromolecules. Here, we present a computational protocol exploiting polarizable embedding hybrid quantum-classical approach and resulting in accurate estimates of redox potentials of biological macromolecules. A special attention is paid to fundamental aspects of the theoretical description such as the effects of environment polarization and of the long-range electrostatic interactions on the computed energetic parameters. Environment (protein and the solvent) polarization is shown to be crucial for accurate estimates of the redox potential: hybrid quantum-classical results with and without account for environment polarization differ by 1.4 V. Long-range electrostatic interactions are shown to contribute significantly to the computed redox potential value even at the distances far beyond the protein outer surface. The approach is tested on simulating reduction potential of cryptochrome 1 protein from Arabidopsis thaliana . The theoretical estimate (0.07 V) of the midpoint reduction potential is in good agreement with available experimental data (−0.15 V). 

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5. 3D Printed Spectroelectrochemical Platform for Redox‐Based Bioelectronics

   https://doi.org/10.1002/smtd.202401843  

   Chen, Chen‐Yu; Kim, Eunkyoung; Zakaria, Fauziah_Rahma; Chu, Monica_J; Wu, Benjamin; Payne, Gregory_F; Bentley, William_E (January 2025, Small Methods)

   Abstract Redox provides unique opportunities for interconverting molecular/biological information into electronic signals. Here, the fabrication of a 3D‐printed multiwell device that can be interfaced into existing laboratory instruments (e.g., well‐plate readers and microscopes) to enable advanced redox‐based spectral and electrochemical capabilities is reported. In the first application, mediated probing is used as a soft sensing method for biomanufacturing: it is shown that electrochemical signal metrics can discern intact mAbs from partially reduced mAb variants (fragmentation), and that these near‐real‐time electrical measurements correlate to off‐line chemical analysis. In the second application,operandospectroelectrochemical measurements are used to characterize a redox‐active catechol‐based hydrogel film: it is shown that electron transfer into/from the film correlates to the molecular switching of the film's redox state with the film's absorbance increasing upon oxidation and the film's fluorescence increasing upon reduction. In the final example, a synthetic biofilm containing redox‐responsiveE. coliis electro‐assembled: it is shown that gene expression can be induced under reducing conditions (via reductive H₂O₂generation) or oxidative conditions (via oxidation of a phenolic redox‐signaling molecule). Overall, this work demonstrates that 3D printing allows the fabrication of bespoke electrochemical devices that can accelerate the understanding of redox‐based phenomena in biology and enable the detection/characterization redox activities in technology. 

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