Synthesis of water-soluble BODIPYs: BODIPY-PEG^†

Applications of BODIPY fluorophores have enabled the expansion of research in modern biomedicine. The characteristics required for their use as fluorescent probes include excitation and emission wavelengths in the near-infrared range (600–800 nm), low biotoxicity, high quantum yields, and water solubility. This last requirement is fundamental for biomedical research, such as in photodynamic therapy, cell labeling, and chemosensors. This work focuses on the design and synthesis of fluorescent molecules that are soluble in aqueous media.

In 1970, Davis and Abuchowsky conducted research on polyethylene glycol molecules and introduced the concept of PEGylation. Polyethylene glycol molecules have been found to provide excellent solubility.

Our approach involves functionalizing compounds 1a, 1b, and 1c with a polyethylene glycol unit to yield a family of water-soluble compounds (Figure 1).

First, a polyethylene glycol unit was synthesized using the methodology described by Krueger et al. two glycol units were incorporated into malonic acid via esterification with an alcohol containing two glycol units (Eq. 1). The malonic glycol ester 3 was successfully obtained, as confirmed by 1H and 13C NMR experiments (Figure 1A).

Regarding the incorporation of the malonic glycol ester into 8-methylthioBODIPY, the methodology described by the Peña-Cabrera group for the addition of active methylenes at the meso position of the BODIPY core was adopted.

This research successfully achieved the synthesis of a new family of water-soluble BODIPY dyes through functionalization with a polyethylene glycol derivative.

Reference

1. Knop, K.; Hoogenboom, R.; Fisher, D.; Schubert, U. S.; Chem. Int. 2010, 49, 6288.