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

• Published in: Organic & biomolecular chemistry Vol. 18; no. 39; pp. 7876 - 7883
• Main Authors: Mhlongo, Neliswa Z, Ebenhan, Thomas, Driver, Cathryn H. S, Maguire, Glenn. E. M, Kruger, Hendrick G, Govender, Thavendran, Naicker, Tricia
• Format: Journal Article
• Language: English
• Published: 14.10.2020
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/d0ob01415j

In this study, a significantly improved method for the synthesis of modular meso -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 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 33 383-80 434 M −1 cm −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. An improved method using microwave irradiation for the synthesis of modular meso -BODIPY derivatives was generated in up to 65% yield. It was then coupled to three different peptides while meso -BODIPY-c(RGDyK) peptide was assessed for its fluorescence imaging applicability.