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Abstract
<p class="first" id="P1">While interactions between carbon monoxide (CO) and mitochondria
have been previously
studied, the methods used to deliver CO (gas or CO-releasing metal carbonyl compounds)
lack subcellular targeting and/or controlled delivery. Thus, the effective concentration
needed to produce changes in mitochondrial bioenergetics is yet to be fully defined.
To evaluate the influence of mitochondrial-targeted versus intracellularly-released
CO on mitochondrial oxygen consumption rates, we developed and characterized flavonol-based
CO donor compounds that differ at their site of release. These molecules are metal-free,
visible light triggered CO donors (photoCORMs) that quantitatively release CO and
are trackable in cells via confocal microscopy. Our studies indicate that at a concentration
of 10 μM, the mitochondrial-localized and cytosolic CO-releasing compounds are similarly
effective in terms of decreasing ATP production, maximal respiration, and the reserve
capacity of A549 cells. This concentration is the lowest to impart changes in mitochondrial
bioenergetics for any CO-releasing molecule (CORM) reported to date. The results reported
herein demonstrate the feasibility of using a structurally-tunable organic photoCORM
framework for comparative intracellular studies of the biological effects of carbon
monoxide.
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