Geometry Relaxation-Induced Large Stokes Shift in Red-Emitting Borondipyrromethenes (BODIPY) and Applications in Fluorescent Thiol Probes

Abstract

2-Thienyl and 2,6-bisthienyl BODIPY derivatives (BS-SS and BS-DS) were prepared that show intense absorption (ε = 65000 M(-1) cm(-1) at 507 nm) and a large Stokes shift (96 nm) vs the small Stokes shift of typical BODIPY (<15 nm). Control compounds with a thienyl unit at the 8-position or phenyl substituents at the 2,6-positions were prepared (BS-1 and 9). BS-1 shows absorption/emission in the blue-shifted range and a small Stokes shift (12 nm). Compound 9 shows absorption in the red-shifted range, but the Stokes shift (<30 nm) is much smaller than that for BS-SS and BS-DS. DFT calculations propose the large Stokes shifts of BS-SS and BS-DS are due to the remarkable geometry relaxation upon photoexcitation and its substantial effect on the energy levels of molecular orbitals. For the dyes with small Stokes shifts, much smaller geometry relaxations were found. The fluorophores were used for fluorescent thiol probes, with 2,4-dinitrobenzenesulfonyl (DNBS) as the fluorescence switch. Both fluorescence OFF-ON and unprecedented ON-OFF transduction were observed, which are attributed to the different photoinduced intramolecular electron-transfer (PET) profile. All the photophysics were rationalized by DFT calculations based on the concept of "electronic states" instead of the very often used approximation of "molecular orbitals".

Molecular Design of UV–vis Absorption and Emission Properties in Organic Fluorophores: Toward Larger Bathochromic Shifts, Enhanced Molar Extinction Coefficients, and Greater Stokes Shifts

“…Thus the thienyl substitute has very little influence on the optoelectronic properties of 13, resulting in a small Stokes shift of only 11 nm. 32 We then move our attention to the differences among 14− 16, where similar substituents are attached at the 2-and 6-positions (Scheme 4). The thienyl substituents have much larger contributions to the HOMO and LUMO of 14 than the phenyl substituent does in 15 ( Figure 8).…”

“…32 The Stokes shift of 15 can be enhanced by a subtle molecular modification. We notice that the key difference between 14 and 15 concerns the electron-donating properties of the substituents at the 2-and 6-positions; i.e., the phenyl substituents in 15 are less electron-donating compared to the thienyl units in 14.…”

“…However, prior to chemical synthesis, one may not be sure which position to attach a substituent in the dye framework to maximize the spectral shift. An even more puzzling question concerns the Stokes shift: although it has been suggested that the rotation of a molecular structure upon its excitation leads to a large Stokes shift, such as in biphenyl, 29 9-t-butylanthracene, 30 pyrazolo-coumarin derivatives, 30 heptamethine cyanine dyes, 31 and BODIPY dyes, 32 there is a lack of detailed guidelines on how to design new fluorophores with such rotating structures and large Stokes shifts; moreover, introducing substituents to a fluorophore framework often shifts the UV−vis absorption and emission spectra of the dye in the same direction. Consequently, the overall change in the Stokes shift remains small.…”

Real-time analysis of composite magnetic nanoparticle disassembly in vascular cells and biomimetic media

“…In the present investigations, small molecule BODIPY fluorophores combining suitable chemical properties with robust, environment-insensitive fluorescence (30,31) were used as the donor-acceptor pair, and a new synthetic strategy was used for their high-yield attachment to PLA via a poly(DL-lactide) glycinate precursor. Notably, this synthetic route does not require de novo polymer synthesis and may be applied directly to create fluorescent labeled derivatives of preformed aliphatic polyesters, thus making the labeled formulations an accurate model of the prototype unlabeled NPs.…”

“…Notably, this synthetic route does not require de novo polymer synthesis and may be applied directly to create fluorescent labeled derivatives of preformed aliphatic polyesters, thus making the labeled formulations an accurate model of the prototype unlabeled NPs. The relatively ineffective energy transfer due to a limited spectral overlap of the two probes having a small Stokes shift, a persistent and remarkable shortcoming of the BODIPY fluorophores often detrimental to their use as fluorescent probes (30), was overcome in this study by increasing the labeling density of MNPs above the threshold of BODIPY 558/568 complex formation. This complex exhibiting excitation and emission maxima at 565 nm and 612 nm, respectively, and presumably representing a dimer with red-shifted fluorescence (21) contributed to improving the sensitivity of the FRET-based degradation assay through participating in a chain of energy transfer events: BODIPY 558/568 → [BODIPY 558/568 ] 2 → BODIPY 630/650 .…”