Synthesis And Properties Of Fluorescent Probes Based On BODIPY Derivatives

Near infrared (NIR) dyes have received considerable attentions in the recent years due to advances in optical imaging, microarrays, tumour detection and electrophoresis and the need to develop labels and optical sensors for biological and medical applications. A key advantage of NIR dyes is that the scattering of light, autofluorescence, and absorption by tissues and cells is minimized. Traditionally, cyanine dyes, such as Cy3or Cy5, have been used for these applications, but poor photostability and low fluorescence quantum yields are often encountered, because rotation and photoisomerization of the flexible structure can result in nonradiative deactivation pathways.Boradiazaindacene (BODIPY) dyes can be seen as rigid and cross-conjugated molecules and possess superior spectral characteristics to those of fluoresceins and rhodamines such as high absorption coefficience, narrow band shapes with high fluorescence quantum yield, insensitive towards pH and solvents polarity, high photostability, et al. The classic BODIPY dyes absorb and emit in the region of480-540nm. Several strategies have been reported to shift the optical properties to the red, such as:(i) aromatic ring fusion;(ii) introduction of aryl substituents in the3,5-and/or1,7-positions of the BODIPY core;(iii) aza-sbustitution of the meso-carbon atom.Based on the above strategies and further introducing functional substituents at meso-position, we designed and synthesized a series of novel visible/NIR fluorescent probes based on BODIPY dyes, the results are summarized as follows: 1. Through weso-substitution, we synthesized three Hg2+probes based-on BODIPY derivatives. The detection limit of Hg2+in one probe approaches2ppb, and Hg2+can also be detected in living cells according to the confocal fluorescence microscopy experiment.2. The emission wavelength of BODIPY is bathochromically shifted into820nm by introducing (dimethylamino)styryl groups at3,5-position and fusion of dihydronaphthalene moieties at β-position. In the presence of H+, its absorption spectrum blue-shifted and the fluorescence intensity increased which can be used as a ratiometric and "turn-on" fluorescent pH probe in the NIR region.3. Introducing strong electron withdrawing cyano-group and ester group at3-,5-positions of BODIPY increases its π-conjugation and red-shift its absorption and emission spectra above630nm. In polar solvent such as methanol, the π-conjugation of the BODIPY core was lost and the solution become colourless. The optical spectra recover after addition of H+. Theoretic calculation suggests that the strong electron-withdrawing groups at α-position stabilized LUMO energy, therefore shift the spectra to the red, in addition, the whole molecule become easy to be attacked by the nucleophilic reagent. In methanol, the solvent molecules attack the meso-carbon atom and destroy the π-conjugation of the BODIPY core, so that the absorption spectra become similar to that of the pyrrole unit. The structure change in different solvents has been confirmed in1H NMR spectra.4. Synthesized a pyrazine fused aza-BODIPY39. Replacement of the meso-carbon atom with nitrogen atom leads to a bathochromically shift of the absorption spectrum to680nm. Addition of ammonium ion produces significant quenching of the fluorescence intensity (>20equivalent) and a visible colorimetric change from green to red-pink. Theoretic calculation indicates that the neighboring BODIPY molecules form H-aggregation through intermolecular hydrogen bonding between the pyrazine moiety with ammonium ions. The excitonic state of the dye aggregate splits into two levels through the interaction of transition dipoles. A transition to the upper state in parallel aggregates having parallel transition moments leads to hypsochromic shift (blue shift). In H-aggregates, the lower state is much stabilized. So the transition from the excited state to the ground state is very fast and happens mostly between the excitonic bands with vanishing dipole moments as a result of which most of the energy losses are non radiative like thermal losses. Due to this reason the H-aggregates have large Stocke’s shift with low fluorescence yield. Compound39can be applied as a NIR ratiometric probe for ammoniumion.