Microwave-assisted synthesis of meso-carboxyalkyl-BODIPYs and an application to fluorescence imaging

In this study, a significantly improved method for the synthesis of a modular meso-BODIPY (boron dipyrromethene) derivative possessing a free carboxylic acid group (which was subsequently coupled to peptides), is disclosed. This method provides a vastly efficient synthetic route with a > threefold higher overall yield than other reports. The resultant meso-BODIPY acid allowed for further easy incorporation into peptides. The meso-BODIPY peptides showed absorption maxima from 495-498 nm and emission maxima from 504-506 nm, molar absorptivity coefficients from 33383-80434 M-1cm-1 and fluorescent quantum yields from 0.508-0.849. The meso-BODIPY-c(RGDyK) peptide was evaluated for plasma stability and (proved to be durable even up to 4 h) was then assessed for its fluorescence imaging applicability in vivo and ex-vivo. The optical imaging in vivo was limited due to autofluorescence, however, the ex-vivo tissue analysis displayed BODIPY-c(RGDyK) internalization and cancer detection thereby making it a novel tumor-integrin associated fluorescent probe while displaying the lack of interference the dye has on the properties of this ligand to bind the receptor.