Ionic Pyridinium–Oxazole Dyads: Design, Synthesis, and Application in Mitochondrial Imaging

We recently developed an oxidative
intramolecular 1,2-amino-oxygenation
reaction, combining gold­(I)/gold­(III) catalysis, for accessing structurally
unique ionic pyridinium–oxazole dyads (PODs) with tunable emission
wavelengths. On further investigation, these fluorophores turned out
to be potential biomarkers; in particular, the one containing −NMe2 functionality (NMe2-POD) was highly selective
for mitochondrial imaging. Of note, because of mitochondria’s
involvement in early-stage apoptosis and degenerative conditions,
tracking the dynamics of mitochondrial morphology with such imaging
technology has attracted much interest. Along this line, we wanted
to build a library of such PODs which are potential mitochondria trackers.
However, Au/Selecfluor, our first-generation catalyst system, suffers
from undesired fluorination of electronically rich PODs resulting
in an inseparable mixture (1:1) of the PODs and their fluorinated
derivatives. In our attempt to search for a better alternative to
circumvent this issue, we developed a second-generation approach for
the synthesis of PODs by employing Cu­(II)/PhI­(OAC)2-mediated
oxidative 1,2-amino-oxygenation of alkynes. Thes newly synthesized
PODs exhibit tunable emissions as well as excellent quantum efficiency
up to 0.96. Further, this powerful process gives rapid access to a
library of NMe2-PODs which are potential mitochondrial
imaging agents. Out of the library, the randomly chosen POD-3g was studied for cell-imaging experiments which showed high mitochondrial
specificity, superior photostability, and appreciable tolerance to
microenvironment changes with respect to commercially available MitoTracker
green.