title: Synthesis, spectroscopic, and in vitro investigations of 2,6-diiodo-BODIPYs with PDT and bioimaging applications.
abstract: A series of five mono-styryl and their corresponding symmetric di-styryl-2,6-diiodo-BODIPYs containing indolyl, pyrrolyl, thienyl or tri(ethylene glycol)phenyl groups were synthesized using Knoevenagel condensations. The yields for the condensation reactions were improved up to 40% using microwave irradiation (90°C for 1h at 400W) due to lower decomposition of BODIPYs upon prolonged heating. The spectroscopic, structural (including the X-ray of a di-styryl-2,6-diiodo-BODIPY) and in vitro properties of the BODIPYs were investigated. The extension of π-conjugation through the 3,5-dimethyls of the known phototoxic 2,6-diiodo-BODIPY 1 produced bathochromic shifts in the absorption and emission spectra, in the order of 63-125nm for the mono-styryl- and 128-220nm for the di-styryl-BODIPYs in DMSO. The largest red-shifts were observed for the indolyl-containing BODIPYs while the largest fluorescence quantum yields were observed for the tri(ethyleneglycol)phenylstyryl-BODIPYs. Among this series, only the mono-styryl-BODIPYs were phototoxic (IC50=2-15μM at 1.5J/cm(2)), and were observed to localize preferentially in the cell ER and mitochondria. On the other hand, the di-styryl-BODIPYs were found to have low or no phototoxicity (IC50>100μM at 1.5J/cm(2)). Among this series of compounds BODIPY 2a shows the most promise for application as photosensitizer in PDT.
authors.affiliation: Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA.
authors.forename: Jaime H
authors.initials: JH
authors.lastname: Gibbs
authors.affiliation: Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA.
authors.forename: Zehua
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
authors.forename: David
authors.initials: D
authors.lastname: Kessel
authors.affiliation: Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA.
authors.forename: Frank R
authors.initials: FR
authors.lastname: Fronczek
authors.affiliation: Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Pakhomova
authors.affiliation: Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA. Electronic address: vicente@lsu.edu.
authors.forename: M Graça H
authors.initials: MG
authors.lastname: Vicente
mesh_terms: D001896:Boron Compounds / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D018360:Crystallography, X-Ray; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008027:Light; D008856:Microscopy, Fluorescence; D008872:Microwaves; D008928:Mitochondria / Q000737:chemistry / Q000378:metabolism; D008968:Molecular Conformation; D009369:Neoplasms / Q000188:drug therapy; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism; D026082:Singlet Oxygen / Q000378:metabolism; D013050:Spectrometry, Fluorescence
chemical_list: C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; D001896:Boron Compounds; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D026082:Singlet Oxygen