The role of molecular interaction between GOD and metal complexes on redox mediation processes

Model-Driven Design of Redox Mediators: Quantifying the Impact of Quinone Structure on Bioelectrocatalytic Activity with Glucose Oxidase

“…Upon establishing a procedure for experimentally determining the bimolecular rate constant for a representative quinone, we applied the same method to a library of 24 additional quinone-based mediators (Scheme 2). This library of quinones was selected to include a structurally and electronically diverse set of redox mediators, including substituted naphthoquinones (1-9), benzoquinones (10)(11)(12)(13)(14)(15)(16)(17), and catechols (18)(19)(20)(21)(22)(23)(24)(25). The calculated bimolecular rate constants for all 25 quinone-based mediators varied significantly from k = (2.5 ± 0.8)×10 1 M -1 s -1 for 2-methoxy-1,4-naphthoquinone (6) to k = (2.29 ± 0.04)×10 6 M -1 s -1 for 4-ethylcatechol (20) with naphthoquinones generally exhibiting lower rate constants than benzoquinones, which in turn exhibited lower rate constants than catechols (kNQ < kBQ < kcatechols).…”

“…While many prior examples have demonstrated the design of diverse redox mediators, such as osmium complexes, quinones, methyl viologen, cobaltocene and ferrocene compounds for a variety of oxidoreductase enzymes, generally only three to five compounds were employed to evaluate the parameters that control electron transfer rates. [11][12][13] Consequently, these insights may be less reliable in designing redox mediators for other enzyme systems. Additionally, a critical work by Kano and co-workers demonstrated the apparent importance of mediator electrostatics in dictating bioelectrocatalytic activity in a peroxidase biosensor.…”

“…As a model enzyme, GOx is ideal because its native electron acceptor (molecular oxygen) can be readily supplanted by exogenous redox mediators such as quinones, and its protein structure, mechanism, kinetics, and electrochemical performance are well-established in the literature. 13,[21][22][23] Similarly, quinones are ubiquitous as both physiological and electrochemical redox mediators, and their role in biological electron transport chains and fundamental electrochemistry has been extensively studied. [24][25][26][27] Furthermore, quinones have been reported to undergo electron transfer with several flavoenzymes, including GOx, via an outer-sphere electron transfer mechanism, thus making them ideal model mediators for studying effects of structural features on apparent electron transfer rates.…”

Model-Driven Design of Redox Mediators: Quantifying the Impact of Quinone Structure on Bioelectrocatalytic Activity with Glucose Oxidase

“…However, existing attempts to elucidate relationships between mediator structure and bioelectrocatalytic activity have relied on a small number of redox mediators to extrapolate structure–activity trends. While many prior works have demonstrated the use of a variety of redox-active molecules (e.g., osmium complexes, quinones, methyl viologen, cobaltocene, and ferrocene derivatives) as enzymatic mediators, these studies often relied on only three to five mediators to evaluate parameters that control electron transfer rates. − As a result, such studies may be less reliable for identifying the design principles necessary to expedite the preparation of novel enzymatic redox mediators.…”

“…The enzyme, GOx, contains a non-dissociable flavin adenine dinucleotide (FAD + /FADH 2 ) cofactor and catalyzes the oxidation of glucose. As a model enzyme, GOx is ideal because its native electron acceptor (molecular oxygen) can be readily supplanted by exogenous redox mediators such as quinones, and its protein structure, mechanism, kinetics, and electrochemical performance are well-established in the literature. ,− …”