Bioconjugatable, PEGylated hydroporphyrins for photochemistry and photomedicine. Narrow-band, near-infrared-emitting bacteriochlorins

Abstract

Synthetic bacteriochlorins absorb in the near-infrared (NIR) region and are versatile analogues of natural bacteriochlorophylls. The utilization of these chromophores in energy sciences and photomedicine requires the ability to tailor their physicochemical properties, including the incorporation of units to impart water solubility. Herein, we report the synthesis, from two common bacteriochlorin building blocks, of five wavelength-tunable, bioconjugatable and water-soluble bacteriochlorins along with two non-bioconjugatable benchmarks. Each bacteriochlorin bears short polyethylene glycol (PEG) units as the water-solubilizing motif. The PEG groups are located at the 3,5-positions of aryl groups at the pyrrolic β-positions to suppress aggregation in aqueous media. A handle containing a single carboxylic acid is incorporated to allow bioconjugation. The seven water-soluble bacteriochlorins in water display Q_y absorption into the NIR range (672–819 nm), sharp emission (21–36 nm full-width-at-half-maximum) and modest fluorescence quantum yield (0.017–0.13). Each bacteriochlorin is neutral (non-ionic) yet soluble in organic (e.g., CH₂Cl₂, DMF) and aqueous solutions. Water solubility was assessed using absorption spectroscopy by changing the concentration ∼1000-fold (190–690 μM to 0.19–0.69 μM) with a reciprocal change in pathlength (0.01–10 cm). All bacteriochlorins showed excellent solubility in water, except for a bacteriochlorin–imide that gave slight aggregation at higher concentrations. One bacteriochlorin was conjugated to a mouse polyclonal IgG antibody for use in flow cytometry with compensation beads for proof-of-principle. The antibody conjugate of B2-NHS displayed a sharp signal upon ultraviolet laser excitation (355 nm) with NIR emission measured with a 730/45 nm bandpass filter. Overall, the study gives access to a set of water-soluble bacteriochlorins with desirable photophysical properties for use in multiple fields.