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

In this study, a significantly improved method for the synthesis of modularmeso-BODIPY (boron dipyrromethene) derivatives 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 resultantmeso-BODIPY acid allowed for further easy incorporation into peptides. Themeso-BODIPY peptides showed absorption maxima from 495-498 nm and emission maxima from 504-506 nm, molar absorptivity coefficients from 33 383-80 434 M(-1)cm(-1)and fluorescent quantum yields from 0.508-0.849. Themeso-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 applicabilityin vivoandex vivo. The optical imagingin vivowas limited due to autofluorescence, however, theex vivotissue 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.