Norcyanine-Carbamates Are Versatile Near-Infrared Fluorogenic Probes

Abstract

Fluorogenic probes in the near-infrared (NIR) region have the potential to provide stimuli-dependent information in living organisms. Here, we describe a new class of fluorogenic probes based on the heptamethine cyanine scaffold, the most broadly used NIR chromophore. These compounds result from modification of heptamethine norcyanines with stimuli-responsive carbamate linkers. The resulting cyanine carbamates (CyBams) exhibit exceptional turn-ON ratios (∼170×) due to dual requirements for NIR emission: carbamate cleavage through 1,6-elimination and chromophore protonation. Illustrating their utility in complex in vivo settings, a γ-glutamate substituted CyBam was applied to imaging γ-glutamyl transpeptidase (GGT) activity in a metastatic model of ovarian cancer. Overall, CyBams have significant potential to extend the reach of fluorogenic strategies to intact tissue and live animal imaging applications.

Targeted Dual-Modal PET/SPECT-NIR Imaging: From Building Blocks and Construction Strategies to Applications

“…We recently reported a non-FRET-based turn-on strategy in the NIR range. Fluorogenic heptamethine cyanine fluorophores were generated by forming norcyanine carbamates (CyBam) [ 150 , 151 ]. This strategy avoids the chemical complexity of a quencher group.…”

NIR‐II Fluorescent Probe for Detecting Trimethylamine Based on Intermolecular Charge Transfer

“…[22][23][24] However, small organic fluorophore molecules attract extensive attention for applications in clinical trials owing to clear chemical structure, high stability, easy metabolism and good biocompatibility. [25][26][27][28][29][30] Very recently, some small organic NIR-II fluorophore molecules were designed and synthesized successfully, which absorbed and emitted light longer than 1000 nm. [31][32][33][34][35][36] They exhibited high water solubility, resolution and signal-to-noise ratio, and have been applied for non-invasive imaging of mouse cerebrovascular system, hindlimb vascular system and lymphatic vasculature.…”

NIRII‐HDs: A Versatile Platform for Developing Activatable NIR‐II Fluorogenic Probes for Reliable In Vivo Analyte Sensing

“…In contrast, the design of activated probes based on the controllable hydroxyl or amino groups of fluorescent dyes (Figure 1a) have broader applications such as the tracer of enzymes, the identification of metal ions, the detection of ROS or reactive sulfur species, etc. [13] However, so far, the dye equipped with hydroxyl or amino functional groups that can be used to design NIR-IIactivatable probes are still rare. This greatly hinders the development of NIR-II probes for in vivo detection.…”