4-4-difluoro-4-bora-3a-4a-diaza-s-indacene and bacteriochlorin

Near infrared (NIR) fluorescent probes are attractive tools for biomedical in vivo imaging due to the relatively deeper tissue penetration and lower background autofluorescence. Activatable probes are turned on only after binding to their target, further improving target to background ratios. However, the number of available activatable NIR probes is limited. In this study, we introduce two types of activatable NIR fluorophores derived from bacteriochlorin: chlorin-bacteriochlorin energy-transfer dyads and boron-dipyrromethene (BODIPY)-bacteriochlorin energy-transfer dyads. These fluorophores are characterized by multiple narrow excitation bands with relatively strong emission in the NIR. Targeted bacteriochlorin-based antibody or peptide probes have been previously limited by aggregation after conjugation. Polyethylene glycol (PEG) chains were added to improve the hydrophilicity without altering pharmacokinetics of the targeting moieties. These PEGylated bacteriochlorin-based activatable fluorophores have potential as targeted activatable, multicolor NIR fluorescent probes for in vivo applications.

Topics: Animals; Antibodies, Monoclonal; Boron Compounds; Cell Line, Tumor; Fluorescent Dyes; Heterografts; Humans; Mice; Neoplasms; Optical Imaging; Polyethylene Glycols; Porphyrins

A series of energy transfer arrays, comprising 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, 587, 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 nonpolar 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 between 500-700 nm, BODIPY-bacteriochlorin arrays should allow for construction of near-IR emitting agents with multiple and broadly tunable absorption bands. Solvent-dielectric constant dependence of Φ

Topics: Biological Assay; Boron Compounds; Infrared Rays; Porphyrins