Generation-collection (redox cycling), using two or more sets of electrodes in close proximity, is an electrochemical technique used for chemical analysis and evaluating electrochemical mechanisms and their physical constants.  The product from oxidation or reduction at one set of electrodes (generator) reaches the neighboring set of electrodes (collector) through diffusion.  There, it produces a current, usually from re-reduction or re-oxidation, respectively, back to the original form. The magnitude of the collector current is proportional to the quantity of product reaching it, which is a function of the efficiency of the mass transfer and the extent of intervening reactions that can enhance or diminish its concentration during the transit time.  Generation-collection at electrode arrays is rich in the number of parameters that can be varied, including the physical nature of the device (geometry, relative placement, size, and number of electrodes), the timing of activating different generator and collector electrodes, and the potential or current that is applied at the electrodes.

We have been developing the application of generation-collection for analysis of dopamine (DA), norepinephrine (NE) and epinephrine (EP).  These catecholamines serve important roles in neurological functions and related diseases.^1,2,3  Electrochemistry at single, small electrodes (i.e. carbon fibers) has been applied extensively for in vivo analysis of individual catecholamines.⁴  However, due to their similarity in chemical structure, it is difficult to simultaneously identify different catecholamines by their oxidation potential.⁵  The generation-collection approach is promising for differentiating catecholamines from each other, especially for DA from NE, which is particularly challenging by other electrochemical means.

The catecholamines undergo an ECC’ mechanism.⁶ This involves a two-electron oxidation (E) to the orthoquinone, followed by a 1,4-addition, resulting in cyclization (C) to the leucoaminochrome with different apparent rate constants specific to the catecholamine.  They are reported to be (in pH 7.4 phosphate buffer): 0.13 ± 0.05 s^-1, 0.98 ± 0.52 s^-1 and 87 ± 10 s^-1 for DA, NE and EP, respectively.⁷  We have demonstrated previously that EP can be differentiated from DA and NE because the orthoquinone of EP does not survive the travel time to collector electrodes as close as 4-µm from the generators.⁸More recently, we have shown that at longer distances, > 20 µm, the collector electrode no longer detects the orthoquinone of NE, too.  A fast bimolecular reaction (C’) can follow the intramolecular cyclization. It involves leucoaminochrome and another orthoquinone, which produces the aminochrome and returns the orthoquinone back to its catechol form, which can oxidize at the generator again. Understanding the distribution of the concentrations of each of these species, how they are affected by each other and by the placement and activation of the electrodes is important in developing the generation-collection approach for quantitative analysis. Thus, it is necessary to understand the fundamental chemistry not only through experiment, but also through modeling and computer simulations. 

We will discuss our progress with the models, simulations, and their accuracy in light of our latest experimental results with generation-collection for quantifying and discriminating catecholamines in mixtures. Our experiments are performed with devices of arrays of coplanar, individually-addressable gold band electrodes patterned on a SiO₂-insulated silicon substrate. A potentiostat is used to apply voltages in a configuration that allows control of multiple working electrodes. The auxiliary and reference electrodes are either on-chip gold elements that serve both functions, or an external platinum flag and Ag/AgCl (saturated KCl), respectively. The models and computer simulations are being developed to exploit the spatial, temporal, and voltage-current relationships of a generation-collection device for applications in analytical chemistry. We are using the general-purpose software platform of COMSOL Multiphysics for building the simulations. This approach may also be extended for determining mechanisms and kinetics in a wider range of electrochemical systems.

References

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3.  Vazey, E. M.; Aston-Jones, G. Frontiers in behavioral neuroscience. 2012, 6

4.  Robinson, D. L., Hermans, A., Seipel, A. T., & Wightman, R. M. Chemical reviews 2008,108(7), 2554-2584.

5.  Hawley, M. D.; Tatawawadi, S. V.; Piekarski, S.; Adams, R. N. Journal of the American Chemical Society 1967, 89, 447-450.

6.  Ciolkowski, E. L.; Maness, K. M.; Cahill, P. S.; Wightman, R. M.; Evans, D. H.; Fosset, B.; Amatore, C. Analytical Chemistry 1994, 66, 3611-3617.

7.  Ciolkowski, E. L.; Cooper, B. R.; Jankowski, J. A.; Jorgenson, J. W.; Wightman, R. M. Journal of the American Chemical Society 1992, 114, 2815-2821.

8.  Hu, M.; Fritsch, I. Analytical Chemistry 2015, 87, 2029−2032.