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Molecular Design of Bioorthogonal Probes and Imaging Reagents Derived from Photofunctional Transition Metal Complexes
journal contribution
posted on 2020-01-09, 14:41 authored by Kenneth Kam-Wing LoConspectusFor more than 15 years, bioorthogonal
chemistry has received increasing
attention due to its successful applications in the detection and
imaging of biomolecules in their native biological environments. The
method typically proceeds with the incorporation of a biological substrate
appended with a bioorthogonal functional group (chemical reporter),
followed by the introduction of the substrate to biological systems.
Biomolecules containing the substrate are then recognized by an exogenously
delivered bioorthogonal probe. Despite the fact that many useful chemical
reporters and bioorthogonal reactions have been developed, most of
the bioorthogonal probes reported thus far are fluorescent dyes. A
limitation is that stringent washing is required due to the interference
caused by the background fluorescence of unreacted probes. Thus, fluorogenic
probes with turn-on emission properties upon bioorthogonal labeling
have been designed as an alternative strategy. These probes are highly
appealing because excellent images can be obtained without the need
for washing steps.Nearly all fluorogenic bioorthogonal probes
designed are essentially
organic dyes, their emission is limited to fluorescence, and the utilization
of the probes is confined to bioimaging applications. Recently, there
has been a growing interest in the bioimaging and therapeutic applications
of luminescent inorganic and organometallic transition metal complexes
due to their intriguing photophysical
and photochemical properties, high membrane permeability, controllable
cellular uptake, intracellular localization, and cytotoxicity. We
anticipate that photofunctional transition metal complexes can be
exploited as valuable bioorthogonal probes due to these appealing
advantages.In this Account, we introduce the molecular design,
photophysical
and photochemical properties, and biological applications of various
bioorthogonal probes and imaging reagents based on photofunctional
transition metal complexes. The presence of a cationic metal center
significantly enhances the bioorthogonal reactivity of the probes,
yet their stability in aqueous solutions can be maintained. Interestingly,
some of these metal complexes are strategically modified to display
phosphorogenic properties, that is, phosphorescence turn-on upon bioorthogonal
labeling reactions. Importantly, these probes not only exhibit favorable
photophysical properties after bioorthogonal labeling, but also efficient
photoinduced singlet oxygen (1O2) generation.
This interesting bioorthogonal reaction-triggered photosensitization
capability allows the modulation of 1O2 generation
efficiency and contributes to the development of controllable photocytotoxic
agents. The exploration of transition metal complex-based probes not
only significantly widens the scope of bioorthogonal labeling but
also further highlights the unique advantages of these complexes in
the design of theranostic reagents. The development of these innovative
reagents is expected to contribute to the basic understanding of biological
processes in living systems and provide exciting opportunities for
new diagnostic and therapeutic applications.
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fluorogenic bioorthogonal probesbioorthogonal probesphotofunctional transition metal complexesturn-on emission propertiescationic metal centertransition metal complex-based probesImaging Reagents Derived1 O 2 generation efficiencydisplay phosphorogenic properties1 O 2photoinduced singlet oxygenPhotofunctional Transition Metal Complexes ConspectusFororganometallic transition metal complexesapplicationbioorthogonal reaction-triggered photosensitization capability
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