Molecular Design of d-Luciferin-Based Bioluminescence and 1,2-Dioxetane-Based Chemiluminescence Substrates for Altered Output Wavelength and Detecting Various Molecules

Abstract

Optical imaging including fluorescence and luminescence is the most popular method for the in vivo imaging in mice. Luminescence imaging is considered to be superior to fluorescence imaging due to the lack of both autofluorescence and the scattering of excitation light. To date, various luciferin analogs and bioluminescence probes have been developed for deep tissue and molecular imaging. Recently, chemiluminescence probes have been developed based on a 1,2-dioxetane scaffold. In this review, the accumulated findings of numerous studies and the design strategies of bioluminescence and chemiluminescence imaging reagents are summarized.

1,2‐Dioxetane‐based Chemiluminescence Probes for Tumor Optical Molecular Imaging

“…Deprotection of the recognition group by reactive species or enzymes leads to the deprotonation of the phenolic hydroxyl, thereby generating chemiluminescence [12] . The 1,2‐dioxetane, a high‐energy four‐membered ring peroxide, provides sufficient energy for the formation of an excited benzoate ester intermediate [13] . The thermal stability of 1,2‐dioxetane was improved through the formation of a spiro ring through the incorporation of adamantane and 1,2‐dioxetane [14–16] …”

“…[12] The 1,2-dioxetane, a high-energy fourmembered ring peroxide, provides sufficient energy for the formation of an excited benzoate ester intermediate. [13] The thermal stability of 1,2-dioxetane was improved through the formation of a spiro ring through the incorporation of adamantane and 1,2-dioxetane. [14][15][16] In 2016, Shabat et al developed a novel chemiluminescent probe based on Schaap's probe by incorporating a fluorophore onto the benzene ring (structure b).…”

Theoretical Study on the Formation and Decomposition Mechanisms of Coelenterazine Dioxetanone

“…Bioluminescence is a natural phenomenon in which biological organisms produce light through chemical reactions, widespread in oceans , (such as jellyfish, cypridina, , luminescent fish, , etc.). Over the past decades, bioluminescence has received great attention due to the high signal-to-noise ratio and high bioluminescence quantum yields. − These advantages of bioluminescence systems make them capable of being successfully applied in real-time monitoring of cell dynamics, gene reporter and regulation, , enzyme immunoassays, molecular imaging, − monitoring of protein interactions, and intracellular Ca 2+ measurements. , …”

Chemiluminescent Probes Based on 1,2‐Dioxetane Structures For Bioimaging

“…Structures of 1,2‐dioxetane‐based chemiluminescent probes mainly include four parts [10] with different functions (Scheme 1B): 1) The phenol part is the main part of the emitter, and as an electron donor, it can be masked by various recognition groups; 2) The methoxy group acts as an electron‐releasing group to form aromatic ester with phenol group and the C−O group of dioxyethane, making π‐π singlet state the lowest excited state; 3) The adamantyl group plays an important role in the stability of the entire structure; 4) The dioxetane moiety is the energy donor for the structure to emit photons. In 1987, Schaap et al ., as a pioneer reported the first example of 1,2‐dioxetane‐type enzyme‐activated chemiluminescent probe, realizing CL imaging of living cells [11] .…”