Mitochondria Targeting Fluorescent Probes Based on through Bond‐Energy Transfer for Mutually Imaging Signaling Molecules H₂S and H₂O₂

Abstract

Reactive signaling molecules participate in varieties of biochemical reactions, and methods to detect their mutual existence and crosstalk are in urgent demand. A benzothiadiazole‐based handle was designed to fluorescently respond to the co‐existence of H2S and H2O2 under pseudo‐physiological conditions on a basis of a thiyl‐radical‐mediated mechanism that accounts for the rapid and efficient domino‐like reaction processes. Then the handle motif was attached to a rhodamine moiety by means of an ethynylene linkage, and achieved a significant H2S–H2O2 mutual response in the mitochondria of living cells. Theoretical calculations supported that a through bond energy transfer mechanism contributes to the drastic fluorescence response.

GSH and H2O2 Co‐Activatable Mitochondria‐Targeted Photodynamic Therapy under Normoxia and Hypoxia

“…In arecent work, we reported abenzothiadiazole (BTD)based MRP handle that possessed an aryl nitro group ortho to ap henyloxyl substituent and reacted with H 2 Sa nd H 2 O 2 under mild conditions (Supporting Information, Figure S1). [14] Thethiyl radical (NO 2 ArSC), once generated by the presence of H 2 Sa nd H 2 O 2 ,w as immediately converted to fluorescent NH 2 ArSO 3 Hi nvolving an intramolecular oxygen transfer process in aqueous solutions (pH 7.4).…”

“…[15] Through hydrogen abstraction in the presence of NO 2 ArSH, the sulfinyl radical is converted back to NO 2 ArSOH, with concomitant generation of the thiyl radical NO 2 ArSC.T he NO 2 ArSH ! NO 2 ArSC reaction is favored by the small bonding dissociation enthalpy (BDE) of SÀHb ond [14] and rapid intramolecular transformation. Theo verall NO 2 ArSH !…”

GSH and H2O2 Co‐Activatable Mitochondria‐Targeted Photodynamic Therapy under Normoxia and Hypoxia

“…In a recent work, we reported a benzothiadiazole (BTD)‐based MRP handle that possessed an aryl nitro group ortho to a phenyloxyl substituent and reacted with H 2 S and H 2 O 2 under mild conditions (Supporting Information, Figure S1) . The thiyl radical (NO 2 ArS .…”

“…The NO 2 ArSH → NO 2 ArS . reaction is favored by the small bonding dissociation enthalpy (BDE) of S−H bond and rapid intramolecular transformation. The overall NO 2 ArSH → NH 2 ArSO 3 H process can be coupled and accelerated by the GSH/GS .…”

Fluorescent Benzothiadiazole Derivatives as Fluorescence Imaging Dyes: A Decade of New Generation Probes

“…The development of BTD‐Mito‐p (Figure 6), a BTD and rhodamine hybrid structure synthesized by Feng and co‐workers, was a breakthrough regarding the molecular architecture and cellular response under a specific condition [103] . The bioprobe was formed as a consequence of the H 2 S‐H 2 O 2 mutual response inside the mitochondrial machinery.…”