Advancements in near-infrared (NIR) fluorescence imaging have enabled greater tissue
penetration depths, high spatial resolution, reduced photon scattering, and minimal
interference from tissue autofluorescence. Hence, NIR fluorophores exist as viable
candidates for biological imaging applications, as well as providing unique insights into
complex biological processes to better understand disease etiology.
In this work, a series of novel boron-based coumarin and rhodamine-like
fluorophores were developed and tested. Initially, modifications to the coumarin
scaffold were investigated to develop more red-shifted dyes, whereby incorporation of
a p-conjugated bridge was determined to be a critical component. Confocal microscopy
studies with A549 lung cancer cells showed clear differences in the intra-cellular
distributions of the fluorophores. The lipophilic carborane coumarin derivatives
exhibited superior selectively within lipid droplets. In contrast, the polar boronic acid
hydrazone-coumarins displayed intracellular localisation within the endoplasmic
reticulum.
A library of boron-containing rhodamine-like probes were also synthesised. All
compounds exhibited near-infrared emission wavelengths with large Stokes shifts.
Furthermore, modifications to the terminal boron moiety were not found to impact the
overall red-shift of the molecules, although increasing the donor group strength
favourably enhanced this shift. The low brightness of some of the probes, related to
rhodamine spirocyclisation, meant that conclusive intracellular localisations could not
be confirmed.
The near-IR emitting nature of the rhodamine-like probes was recognised as a
highly advantageous tool for bioimaging applications. Two fluorescent-labelled ligands
with varying linker lengths, of the allosteric adamantyl benzamide P2X7R antagonist
were prepared, based on the para-MIDA ester rhodamine-like fluorophore. Both probes
were utilised in preliminary fluorescence studies, whereby the near-IR emitting nature
of the fluorophore was retained despite conjugation to biomolecules. As well, a longer
emission wavelength was observed with a shorter linker length.
This research ultimately highlights the versatility of boron as a unique element in
fluorescence and biological imaging applications
