Spirostrain-Accelerated Chemiexcitation of Dioxetanes Yields Unprecedented Detection Sensitivity in Chemiluminescence Bioassays

Rozan Tannous, Omri Shelef, Sara Gutkin, Maya David, Thomas Leirikh, Liang Ge, Qais Jaber, Qingyang Zhou, Pengchen Ma, Micha Fridman, Urs Spitz, Kendall N. Houk*, Doron Shabat*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Chemiluminescence is a fascinating phenomenon that involves the generation of light through chemical reactions. The light emission from adamantyl-phenoxy-1,2-dioxetanes can glow from minutes to hours depending on the specific substituent present on the dioxetane molecule. In order to improve the light emission properties produced by these chemiluminescent luminophores, it is necessary to induce the chemiexcitation rate to a flash mode, wherein the bulk of light is emitted instantly rather than slowly over time. We report the realization of this goal through the incorporation of spirostrain release into the decomposition of 1,2-dioxetane luminophores. DFT computational simulations provided support for the hypothesis that the spiro-cyclobutyl substituent accelerates chemiexcitation as compared to the unstrained adamantyl substituent. Spiro-linking of cyclobutane and oxetane units led to greater than 100-fold and 1000-fold emission enhancement, respectively. This accelerated chemiexcitation rate increases the detection sensitivity for known chemiluminescent probes to the highest signal-to-noise ratio documented to date. A turn-ON probe, containing a spiro-cyclobutyl unit, for detecting the enzyme β-galactosidase exhibited a limit of detection value that is 125-fold more sensitive than that for the previously described adamantyl analogue. This probe was also able to instantly detect and image β-gal activity with enhanced sensitivity in E. coli bacterial assays.

Original languageEnglish
Pages (from-to)28-42
Number of pages15
JournalACS Central Science
Volume10
Issue number1
DOIs
StatePublished - 24 Jan 2024

Funding

FundersFunder number
National Science FoundationCHE-2153972
University of California, Los Angeles
San Diego Supercomputer Center
National Natural Science Foundation of China22103060
Israel Science Foundation

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