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Abstract Next generation chemiluminescent iridium 1,2‐dioxetane complexes have been developed which consist of the Schaap's 1,2‐dioxetane scaffold directly attached to the metal center. This was achieved by synthetically modifying the scaffold precursor with a phenylpyridine moiety, which can act as a ligand. Reaction of this scaffold ligand with the iridium dimer [Ir(BTP)2(μ‐Cl)]2(BTP=2‐(benzo[b]thiophen‐2‐yl)pyridine) yielded isomers which depict ligation through either the cyclometalating carbon or, interestingly, the sulfur atom of one BTP ligand. Their corresponding 1,2‐dioxetanes display chemiluminescent responses in buffered solutions, exhibiting a single, red‐shifted peak at 600 nm. This triplet emission was effectively quenched by oxygen, yielding in vitro Stern‐Volmer constants of 0.1 and 0.009 mbar−1for the carbon‐bound and sulfur compound, respectively. Lastly, the sulfur‐bound dioxetane was further utilized for oxygen sensing in muscle tissue of living mice and xenograft models of tumor hypoxia, depicting the ability of the probe chemiluminescence to penetrate biological tissue (total flux ∼106 p/s).
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Chemiexcitation Acceleration of 1,2‐Dioxetanes by Spiro‐Fused Six‐Member Rings with Electron‐Withdrawing Motifs
Abstract The chemiluminescent light‐emission pathway of phenoxy‐1,2‐dioxetane luminophores attracts growing interest within the scientific community. Dioxetane probes undergoing rapid flash‐type chemiexcitation exhibit higher detection sensitivity than those with a slow glow‐type chemiexcitation rate. We discovered that dioxetanes fused to non‐strained six‐member rings, with hetero atoms or inductive electron‐withdrawing groups, present both accelerated chemiexcitation rates and elevated chemical stability compared to dioxetanes fused to four‐member strained rings. DFT computational simulations supported the chemiexcitation acceleration observed by spiro‐fused six‐member rings with inductive electron‐withdrawing groups of dioxetanes. Specifically, a spiro‐dioxetane with a six‐member sulfone ring exhibited a chemiexcitation rate 293‐fold faster than that of spiro‐adamantyl‐dioxetane. A turn‐ON dioxetane probe for the detection of the enzyme β‐galactosidase, containing the six‐member sulfone unit, exhibited a S/N value of 108 in LB cell growth medium. This probe demonstrated a substantial increase in detection sensitivity towardsE. colibacterial cells expressing β‐galactosidase, with an LOD value that is 44‐fold more sensitive than that obtained by the adamantyl counterpart. The accelerated chemiexcitation and the elevated chemical stability presented by dioxetane containing a spiro‐fused six‐member ring with a sulfone inductive electron‐withdrawing group, make it an ideal candidate for designing efficient turn‐on chemiluminescent probes with exceptionally high detection sensitivity.
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- Award ID(s):
- 2153972
- PAR ID:
- 10628043
- Publisher / Repository:
- Wiley VCH
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 63
- Issue:
- 46
- ISSN:
- 1433-7851
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1002/anie.202410057
