Carbon monoxide is an endogenously produced signalling molecule that is known to exert cytoprotective and homeostatic regulatory functions.<sup> </sup>Due to its high affinity for heme proteins, one of the recognized targets for CO are mitochondria and their electron transport chain. To date, there are four reported CORMs (CORM-2, CORM-3, CORM-A1, and CORM-401) that have been used as CO donors in mitochondrial studies. However, the differences with respect to their cell penetration, localization and solution-driven CO release chemistry could make the comparison of mitochondrial response data for these systems challenging. To investigate the impact of mitochondrial-specific CO delivery, we have designed and characterized the first mitochondrial-targeted, visible light-triggered CO-releasing molecule. This compound is trackable (green emission) and triggarable with visible light to deliver CO intracellularly. This photoCORM was tested in the context of the effect of CO release on mitochondrial bioenergetics (including oxygen consumption rates (OCR) and glycolysis (ECAR)) which are compared to results from a cytosolic analogue. These studies provide insight into the effects of CO delivery in proximity to mitochondria versus cytosolic delivery.

Mitochondrial-targeted organic photoCORM

255th National Meeting (2018)

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