Sense and Release: A Thiol-Responsive Flavonol-Based Photonically Driven Carbon Monoxide-Releasing Molecule That Operates via a Multiple-Input AND Logic Gate

Molecular structures capable of intracellular information processing that couple responses from biomarker signals to the release of drug molecules represent intelligent delivery systems. Herein we report a chemophotonically driven, sense-of-logic carbon monoxide-releasing molecule (SL-photoCORM). This extended flavonol motif operates via an AND logic gate by first sensing the cellular environment via detection of thiols and then releasing CO when triggered with visible light and O-2. Overall, this approach couples the detection of a cellular redox biomarker with the ability to release a small molecule gasotransmitter known to trigger pathways involved in pro- and anti-inflammatory effects in a dose dependent manner. Significantly, the fluorescence properties of the flavonol-based SL-photoCORM produce a series of chemophotonic input responses via two photo chromatic switches (blue-to-green and green-to-colorless), leading to trackability and spatiotemporal control of CO release. Examination of the O-2 requirements of the CO release step revealed that the SL-photoCORM is suitable for use under conditions of variable cellular levels of O-2. These combined properties within a single-molecular framework advance the field of CO-releasing molecules by providing feedback on the diversity and complexity of the cellular environment prior to CO release.