Tandem activity-based sensing and labeling strategy for reactive oxygen species imaging
View Patent ↗Selective probes provide tandem activity-based sensing and labeling of reactive oxygen species (ROS), such as hydrogen peroxide, peroxynitrite, and organic peroxides.
1 . A reactive oxygen species (ROS) sensor compound comprising-having a structure:
wherein:
R1 is OR5 or NR6R7, wherein R5, R6 and R7 are independently H, C1-C18 optionally substituted, optionally hetero-hydrocarbyl, or optionally substituted heteroatom, and R6/R7 are optionally joined to form a ring;
R2 is O, S, Se or Te, or an oxidized chalcogen selected from SO, SO 2 , SS, SOS, SSS, SeO, SeO 2 , SeS, SeOS, SeSS, TeO, TeO 2 , TeS, TeOS, and TeSS; or CR8R9, SiR8R9, GeR8R9, or PR8R9; or NR10, BR10, or PR10; wherein R8-R10 are independently H, C1-C18 optionally substituted, optionally hetero-hydrocarbyl, or optionally substituted heteroatom;
R3 is O, S, Se, Te, or NR11, wherein R11 is H, C1-C18 optionally substituted, optionally hetero-hydrocarbyl, or optionally substituted heteroatom; and
R4 is C, Si, C═O, or C═NR12, wherein R12 is H, C1-C18 optionally substituted, optionally hetero-hydrocarbyl, or optionally substituted heteroatom;
or a salt, hydrate or stereoisomer of the sensor compound.
2 . The compound of claim 1 , wherein:
R1 is OR5 or NR6R7, wherein R5, R6 and R7 are independently H or C1-C18 optionally substituted, optionally hetero-alkyl, and R6/R7 are optionally joined to form a ring.
3 . The compound of claim 1 , wherein:
R2 is O, S, Se or Te, or an oxidized chalcogen selected from SO, SO 2 , SS, SOS, SSS, SeO, SeO 2 , SeS, SeOS, SeSS, TeO, TeO 2 , TeS, TeOS, and TeSS; or CR8R9, SiR8R9, GeR8R9, or PR8R9; or NR10, BR10, or PR10; wherein R8-R10 are independently H or C1-C18 optionally substituted, optionally hetero-alkyl.
4 . The compound of claim 1 , wherein:
R3 is O, S, Se, Te, or NR11, wherein R11 is H, C1-C18 optionally substituted, optionally hetero-alkyl.
5 . The compound of claim 1 , wherein:
R4 is C, Si, C═O, or C═NR12, wherein R12 is H, C1-C18 optionally substituted, optionally hetero-alkyl.
6 . The compound of claim 1 , wherein:
R1 is OR5 or NR6R7, wherein R5, R6 and R7 are independently H or C1-C18 optionally substituted, optionally hetero-alkyl, and R6/R7 are optionally joined to form a ring;
R2 is O, S, Se or Te, or an oxidized chalcogen selected from SO, SO 2 , SS, SOS, SSS, SeO, SeO 2 , SeS, SeOS, SeSS, TeO, TeO 2 , TeS, TeOS, and TeSS; or CR8R9, SiR8R9, GeR8R9, or PR8R9; or NR10, BR10, or PR10; wherein R8-R10 are independently H or C1-C18 optionally substituted, optionally hetero-alkyl;
R3 is O, S, Se, Te, or NR11, wherein R11 is H, C1-C18 optionally substituted, optionally hetero-alkyl; and
R4 is C, Si, C═O, or C═NR12, wherein R12 is H, C1-C18 optionally substituted, optionally hetero-alkyl.
7 . The compound of claim 1 , wherein:
R1 is OMe or NR6R7, wherein R6 and R7 are independently C1-C4 optionally substituted, optionally hetero-alkyl, and R6/R7 are optionally joined to form a ring.
8 . The compound of claim 1 , wherein:
R2 is O or Si(CH 3 ) 2 .
9 . The compound of claim 1 , wherein:
R3 is O.
10 . The compound of claim 1 , wherein:
R4 is C═O.
11 . The compound of claim 1 , wherein:
R1 is OMe or NR6R7, wherein R6 and R7 are independently C1-C4 optionally substituted, optionally hetero-alkyl, and R6/R7 are optionally joined to form a ring;
R2 is O or Si(CH 3 ) 2 ;
R3 is O; and
R4 is C═O.
12 . The compound of claim 1 , having a structure:
13 . The compound of claim 1 , having a structure:
14 . The compound of claim 1 , having a structure:
15 . The compound of claim 1 , which is a bromide (Br − ) salt of the compound.
16 . A method of using the compound of claim 1 , comprising the step of reacting the compound with a ROS, thereby selectively detecting the ROS.
17 . The method of claim 16 , wherein the ROS is selected from hydrogen peroxide (H 2 O 2 ), peroxynitrite, and organic peroxides.
18 . The method of claim 16 , wherein the reacting step provides boronate oxidation sensing or quinone methide labeling upon reaction with the ROS.
19 . The method of claim 16 , wherein the reacting step provides tandem boronate oxidation sensing and quinone methide labeling upon reaction with the ROS.
20 . The method of claim 16 , wherein the reacting step provides tandem boronate oxidation sensing and quinone methide labeling upon reaction with the ROS, to covalently trap the sensor compound in a cell and thereby provide a stain that preserves spatial information on localized ROS fluxes.