Photoactivatable BODIPYs Designed To Monitor the Dynamics of Supramolecular Nanocarriers

Abstract

Self-assembling nanoparticles of amphiphilic polymers can transport hydrophobic molecules across hydrophilic media and, as a result, can be valuable delivery vehicles for a diversity of biomedical applications. Strategies to monitor their dynamics noninvasively and in real time are, therefore, essential to investigate their translocation within soft matrices and, possibly, rationalize the mechanisms responsible for their diffusion in biological media. In this context, we designed molecular guests with photoactivatable fluorescence for these supramolecular hosts and demonstrated that the activation of the fluorescent cargo, under optical control, permits the tracking of the nanocarrier translocation across hydrogel matrices with the sequential acquisition of fluorescence images. In addition, the mild illumination conditions sufficient to implement these operating principles permit fluorescence activation within developing Drosophila melanogaster embryos and enable the monitoring of the loaded nanocarriers for long periods of time with no cytotoxic effects and no noticeable influence on embryogenesis. These photoresponsive compounds combine a borondipyrromethene (BODIPY) chromophore and a photocleavable oxazine within their covalent skeleton. Under illumination at an appropriate activation wavelength, the oxazine ring cleaves irreversibly to bring the adjacent BODIPY fragment in conjugation with an indole heterocycle. This structural transformation shifts bathochromically the BODIPY absorption and permits the selective excitation of the photochemical product with concomitant fluorescence. In fact, these operating principles allow the photoactivation of BODIPY fluorescence with large brightness and infinite contrast. Thus, our innovative structural design translates into activatable fluorophores with excellent photochemical and photophysical properties as well as provides access to a general mechanism for the real-time tracking of supramolecular nanocarriers in hydrophilic matrices.

A Photoactivatable Far-Red/Near-Infrared BODIPY To Monitor Cellular Dynamics in Vivo

“…35 Illumination of 12 at a λ Ac where its 2-nitrobenzyl fragment absorbs cleaves the 2H,4H- [1,3]oxazine heterocycle irreversibly to produce 2 and 5, in agreement with the photochemical behavior of the parent system (1). 27 Consistently, absorption spectra (Figure 4), recorded sequentially during the photolytic transformation in toluene, reveal a decrease in the BODIPY absorption of 12 with the concomitant appearance and growth of the characteristic band of 5. Similarly, the corresponding emission spectra (inset of Figure 4) show the developing fluorescence of the photochemical product and high-performance liquid chromatography (HPLC) traces (Figure 4) further confirm the gradual conversion of 12 into 5.…”

“…The operating principles to activate the fluorescence of our original photoactivatable BODIPY (1 in Figure 1) relied on the irreversible cleavage of a 2H,4H- [1,3]oxazine heterocycle upon illumination at λ Ac . 27 This photochemical reaction extends the electronic delocalization of the BODIPY chromophore over the adjacent 3H-indole auxochrome in the resulting product (3 in Figure 1). Concomitantly, the S 0 → S 1 absorption shifts bathochromically to allow the excitation of 3 at a λ Ex where 1 cannot absorb and, hence, the activation of fluorescence with infinite contrast.…”

Recent chemo‐/biosensor and bioimaging studies based on indole‐decorated BODIPYs

“…Apart from their sensing properties and applications, indole–BODIPY conjugates have been also used and studied in different disciplines for diverse purposes including assessing fluorescence properties, designing novel supramolecular scaffolds and structures, investigating optical characteristics, and engineering novel solar cells . However, here we aim to emphasize the capability and practicability of indole–BODIPY conjugates for sensing chemical and/or biological entities and for bioimaging studies, therefore the above‐mentioned applications in other fields were regarded as being out of the scope of the present article.…”

3‐Formyl‐BODIPY Phenylhydrazone as a Chromo‐Fluorogenic Probe for Selective Detection of NO2 (g)

“…Condensation of benzaldehyde with 3‐ethyl‐2,4‐dimethylpyrrole, followed by oxidation with 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ), deprotonation with triethylamine (TEA) and treatment with boron trifluoride led to meso ‐phenyl BODIPY 1 according to literature reports . Subsequently, one methyl group at the 3‐position was selectively oxidized with DDQ in THF/H 2 O to give the corresponding aldehyde 2 . Finally, the treatment of 2 with 4‐hydrazinobenzoic acid in refluxing ethanol gave the phenylhidrazone derivative P1 in almost quantitative yield.…”

“…[15] Subsequently,o ne methylg roup at the 3-position was selectively oxidized with DDQ in THF/H 2 Ot og ive the corresponding aldehyde 2. [16] Finally,the treatment of 2 with 4-hydrazinobenzoic acid in refluxinge thanol gave the phenylhidrazone derivative P1 in almost quantitative yield. P1 was fully characterized by 1 HNMR, 13 CNMR and MS (see the Supporting Information for details).…”