CO Sense and Release Flavonols: Progress toward the Development of an Analyte Replacement PhotoCORM for Use in Living Cells

Carbon monoxide (CO)
is a signaling molecule in humans. Prior research
suggests that therapeutic levels of CO can have beneficial effects
in treating a variety of physiological and pathological conditions.
To facilitate understanding of the role of CO in biology, molecules
that enable fluorescence detection of CO in living systems have emerged
as an important class of chemical tools. A key unmet challenge in
this field is the development of fluorescent analyte replacement probes
that replenish the CO that is consumed during detection. Herein, we
report the first examples of CO sense and release molecules that involve
combining a common CO-sensing motif with a light-triggered CO-releasing
flavonol scaffold. A notable advantage of the flavonol-based CO sense
and release motif is that it is trackable via fluorescence in both
its pre- and postsensing (pre-CO release) forms. In vitro studies
revealed that the PdCl2 and Ru­(II)-containing CORM-2 used
in the CO sensing step can result in metal coordination to the flavonol,
which minimizes the subsequent CO release reactivity. However, CO
detection followed by CO release is demonstrated in living cells,
indicating that a cellular environment mitigates the flavonol/metal
interactions.