An H₂S‐Sensing/CO‐Releasing Flavonol That Operates via Logic Gates

Abstract

Signaling molecules, including H2S and CO, are involved in a complex interplay within cells to maintain cellular homeostasis. In order to investigate the intracellular interplay of different gasotransmitters, new molecular tools are needed that combine sensing and release capabilities of different small molecules in a single, multifunctional, and highly-regulated molecular platform. This report gives the first example of a combined H2S sensor/CO-releasing molecule. This flavonol-based molecular tool operates intracellularly via a highly regulated AND logic gated input-output sequence and provides fluorescent feedback for the H2S detection and CO release steps. This linear sequence can be combined with a fluorescent molecular sensor for CO detection via a third distinct emission. Overall, this is the first molecular framework that can combine the sensing of H2S with the controlled release of CO, two gaseous molecules that are known to exhibit reciprocal regulation and have overlapping targets in cellular environments.

Metal-free carbon monoxide-releasing micelles undergo tandem photochemical reactions for cutaneous wound healing

“…The unmasking of the phenolic groups of 3-HF derivatives led to a large Stokes shi, which was previously used for the design of ratiometric uorescent probes. 51 Recently, Berreau and coworkers [32][33][34][35][36] ingeniously found that extended 3-HF derivatives could release CO under visible light irradiation. In this case, the uorescent extended 3-HF moieties were transformed into nonemissive 3-(benzoyloxy)-2-naphthalenecarboxylic acid (3-BNA) species, enabling self-reporting CO release.…”

“…Notably, the hydroxyl groups of extended 3-HF have been successfully masked by thiol-, 35 H 2 S-, 36 and H 2 O 2 (ref. 37)-reactive moieties and photo-triggered CO release could be manipulated in a logical manner.…”

“…Although metal carbonyls hold great promise in both laboratory and clinical investigations, 9,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] the development of metal-free CORMs has recently been receiveing increasing attention. 27 In this context, boranocarbonates, 28 CO-releasing prodrugs operated in a "click and release" manner, [29][30][31] and photoresponsive organic CORMs such as 3-hydroxyavone (3-HF) derivatives, [32][33][34][35][36][37] xanthene-9-carboxylic acid, 38 BODIPY derivatives, 39 and aromatic a-diketone derivatives 40 have been developed.…”

Tracking CO Release in Cells via the Luminescence of Donor Molecules and/or their By‐Products

“…The 3‐hydroxyflavone and 3‐hydroxyquinolone photoCORM motifs are easily modified structures that can be customized for a variety of applications involving trackable CO delivery. These include sense and release applications wherein the CO‐releasing 3‐OH unit in 18 is unmasked for CO release only in the presence of a specific bioanalyte ,,…”

“…These include sense and release applications wherein the CO-releasing 3-OH unit in 18 is unmasked for CO release only in the presence of a specific bioanalyte. [32,33,35]…”