BODIPY–Bacteriochlorin Energy Transfer Arrays: Toward Near-IR Emitters with Broadly Tunable, Multiple Absorption Bands

Abstract

A series of energy transfer arrays, comprising of a near-IR absorbing and emitting bacteriochlorin, and BODIPY derivatives with different absorption bands in the visible region (503 – 668 nm) have been synthesized. Absorption band of BODIPY was tuned by installation of 0, 1, or 2 styryl substituents [2-(2,4,6-trimethoxyphenyl)ethenyl], which leads to derivatives with absorption maxima at 503 nm, 587 nm, and 668 nm, respectively Efficient energy transfer (>0.90) is observed for each dyad, which is manifested by nearly exclusive emission from bacteriochlorin moiety upon BODIPY excitation. Fluorescence quantum yield of each dyad in non-polar solvent (toluene) is comparable with that observed for corresponding bacteriochlorin monomer, and is significantly reduced in solvent of high dielectric constants (DMF), most likely by photoinduced electron transfer. Given the availability of diverse BODIPY derivatives, with absorption in 500–700 nm, BODIPY-bacteriochlorin arrays should allow for construction of near-IR emitting agents with multiple and broadly tunable absorption bands. Solvent-dielectric constants dependence of Φf in dyads gives an opportunity to construct environmentally-sensitive fluorophores and probes.

Activatable Near-Infrared Fluorescence Imaging Using PEGylated Bacteriochlorin-Based Chlorin and BODIPY-Dyads as Probes for Detecting Cancer

“…19 The energy transfer dyads, chlorin-bacteriochlorin and BODIPY-bacteriochlorin, were developed to create NIR fluorophores with a common energy acceptor. 21,22,24 When these fluorophores were conjugated to targeting moieties, they became activatable imaging probes based on a FRET mechanism, a phenomenon that has been previously reported. 19,20 We initially examined these compounds using hGSA as a targeting moiety and then used mAb for targeting.…”

“…Fluorescence quantum yields (Φ f ) of the bacteriochlorin components of dyads, where bacteriochlorin is directly excited (at λ exc = 515 nm and 530 nm, for NMP6 and NMP7, respectively), corresponds well with that reported previously for analogous bacteriochlorin monomers in toluene. 24 In DMF however, the Φ f of bacteriochlorin components in dyads is slightly reduced (1.25 fold for NMP6 and 1.2-fold for NMP7), compared to that observed in toluene. This reduction of Φ f is attributed to the competitive photoinduced electron transfer, which is facilitated in solvents of high dielectric constants.…”

“…[33][34][35] Although in vitro assays of mAbbased probes using chlorin-bacteriochlorin energy transfer dyads (NMP6 and NMP7) appeared hydrophilic, the fluorescence images in peritoneal cancer murine models were unsatisfactory probably because conjugation reaction with NMP6 and NMP7 altered the pharmacokinetics of antibody, resulted in insufficient delivery and activation of fluorescence signal. By exchanging the energy donor from chlorin to BODIPY, which possesses higher polarity and superior extinction coefficient in green light, 24 the BODIPY-bacteriochlorin energy transfer dyads (NMP11 and NMP12) were more efficient and therefore able to readily image the cancers with high sensitivity and specificity. (Figure 6 and Figure 7).…”

“…The synthesis methods of chlorin-bacteriochlorin energy-transfer dyads, NMP6 and NMP7, and BODIPY bacteriochlorin energy-transfer dyads, NMP11 and NMP12, have been published. 22,24 hGSA was incubated with each NMP-NHS ester at a ratio of 1:5 in 0.1 M Na2HPO4 (pH8.6) at room temperature for 1 h, followed by purification with a size exclusion column (PD-10; GE Healthcare, Piscataway, NJ). The NMP labeling mAb was also produced by reacting mAb with each NMP at a ratio of 1:10, respectively, in the same manner as hGSA-NMP conjugates.…”

Amphiphilic Near-IR-Emitting 3,5-Bis(2-Pyrrolylethenyl)BODIPY Derivatives: Synthesis, Characterization, and Comparison with Other (Hetero)Arylethenyl-Substituted BODIPYs

“…24,25 We also examined BODIPY with (2,4,6-trialcoxyaryl)ethenyl substituents (2, Chart 1), which absorbs at 668 nm and functions as an excellent energy donor for bacteriochlorins. 26 However, this absorption and emission maxima are sub-optimal for in vivo application, therefore we envisioned, that 2-pyrrolylethenyl substituents should provide a desirable batochromic shift, and nitrogen on pyrrole moiety should provide a convenient synthetic handle to attach hydrophilic group.…”