Near-Infrared Dioxetane Luminophores with Direct Chemiluminescence Emission Mode

• Published in: Journal of the American Chemical Society Vol. 139; no. 37; pp. 13243 - 13248
• Main Authors: Green, Ori, Gnaim, Samer, Blau, Rachel, Eldar-Boock, Anat, Satchi-Fainaro, Ronit, Shabat, Doron
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 20.09.2017; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; CATALYZED CHEMILUMINESCENCE; SUBSTITUTED DIOXETANE; ALKALINE-PHOSPHATASE; IN-VIVO; HYDROGEN-PEROXIDE; MYELOPEROXIDASE ACTIVITY; BETA-GALACTOSIDASE ACTIVITY; FLUORESCENT-PROBE; LIVING CELLS; QUANTUM DOTS
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.7b08446

Chemiluminescent luminophores are considered as one of the most sensitive families of probes for detection and imaging applications. Due to their high signal-to-noise ratios, luminophores with near-infrared (NIR) emission are particularly important for in vivo use. In addition, light with such long wavelength has significantly greater capability for penetration through organic tissue. So far, only a few reports have described the use of chemiluminescence systems for in vivo imaging. Such systems are always based on an energy-transfer process from a chemiluminescent precursor to a nearby emissive fluorescent dye. Here, we describe the development of the first chemiluminescent luminophores with a direct mode of NIR light emission that are suitable for use under physiological conditions. Our strategy is based on incorporation of a substituent with an extended π-electron system on the excited species obtained during the chemi­excitation pathway of Schaap’s adamant­ylidene-dioxetane probe. In this manner, we designed and synthesized two new luminophores with direct light emission wavelength in the NIR region. Masking of the luminophores with analyte-responsive groups has resulted in turn-ON probes for detection and imaging of β-galactosidase and hydrogen peroxide. The probes’ ability to image their corresponding analyte/enzyme was effectively demonstrated in vitro for β-galactosidase activity and in vivo in a mouse model of inflammation. We anticipate that our strategy for obtaining NIR luminophores will open new doors for further exploration of complex biomolecular systems using non-invasive intra­vital chemiluminescence imaging techniques.