Phosphorogenic Bioorthogonal Probes Derived from Transition Metal Complexes as New Bioimaging Reagents and Photofunctional Therapeutic Agents
DescriptionThe aim of this project is the development of inorganic and organometallic transition metal complexes as new phosphorogenic bioorthogonal probes for applications as bioimaging reagents and photofunctional therapeutic agents. Bioorthogonal labeling has emerged as a powerful method to visualize biomolecules in their native biological environments. The labeling process involves a two-step modification scheme: 1) the incorporation of a biomolecule modified with a chemical reporter into live cells and organisms, 2) specific reaction of the modified biomolecule with a bioorthogonal probe carrying the complementary functionality. To date, most bioorthogonal probes have been derived from fluorescent dyes. A drawback to these dyes is that stringent washing is required due to the interference caused by the intense background fluorescence of unreacted probes. Thus, fluorogenic probes with turn-on emission properties upon bioorthogonal labeling have been developed as an alternative strategy. These probes are very appealing because high-quality images can be obtained without the need of washing steps. Since almost all the fluorogenic bioorthogonal probes reported thus far are derived from organic dyes, the emission is limited to fluorescence and the utilization of the probes is confined to bioimaging applications. In recent years, there has been an emerging interest in the bioimaging and therapeutic applications of luminescent transition metal complexes due to their intriguing photophysical and photochemical properties, membrane permeability, and controllable cellular uptake properties. In this project, we will build upon these interesting features and develop transition metal complexes that exhibit phosphorogenic properties, i.e., phosphorescence turn-on upon bioorthogonal labeling reactions. Importantly, our target probes will not only display favorable photophysical properties after bioorthogonal labeling, but also efficient photoinduced singlet oxygen (1O2) generation. This interesting bioorthogonal reaction-triggered photosensitization capability will allow the modulation of1O2generation efficiency and contribute to the development of controllable photocytotoxic agents. Additionally, through the use of cell-penetrating peptides, tumor-targeting molecules, and protein tags, we will be able to design new agents for organelle-targeting, cancer cell-selective photodynamic therapy (PDT) applications, and chromophore-assisted light inactivation (CALI), respectively. The exploration of phosphorogenic inorganic and organometallic probes will significantly widen the scope of bioorthogonal labeling, which will be welcomed by the chemical biology, biochemistry, and cell biology communities. The results generated from this project will highlight the role of luminescent transition metal complexes in the development of theranostic reagents, which will contribute to the basic understanding of biological processes in living systems and provide exciting opportunities for a range of diagnostic and therapeutic applications.
|Effective start/end date||1/01/20 → …|