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 1 h at 400 W) due to lower decomposition of BODIPYs upon prolonged heating. The spectroscopic, structural (including the X-ray of a di-styryl-2,6-diiodo-BODOPY) 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 59–125 nm for the mono-styryl- and 126–220 nm 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 = 2–15 µM at 1.5 J/cm2), 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 > 100 µM at 1.5 J/cm2). Among this series of compounds BODIPY 2a shows the most promise for application as photosensitizer in PDT.

Synthesis of 3,8‐Dichloro‐6‐ethyl‐1,2,5,7‐tetramethyl–BODIPY from an Asymmetric Dipyrroketone and Reactivity Studies at the 3,5,8‐Positions

“…However, it is known that the α-methyl groups of BODIPYs can react with aldehydes under Knoevenagel condensation conditions, [17] providing an additional reactive site for functionalization of BODIPY 1a . Furthermore, we anticipated that this methyl group could be regioselectively oxidized under mild conditions, providing functionality for further derivatization and/or conjugation of the BODIPY.…”

“…The monostyryl-BODIPY displays further redshifted absorbance and emission spectra (see below, Table 1 and Figure 7) and potential applications as a fluorescent sensor and photosensitizer. [17] …”

“…[2] For example, the α-methyl groups on BODIPY platform a undergo Knoevenagel condensations with various aldehydes, to produce the corresponding styryl-BODIPYs that display significant redshifted absorption and emission spectra. [17] On the other hand, BODIPY platform b bearing 3,5-chloro groups undergoes milder Pd 0 -catalyzed cross-coupling reactions and nucleophilic substitution reactions at these positions, producing a variety of functionalized BODIPYs for various applications. [18] Functionalizations at the 8-position of BODIPYs are reported for platform c , [15, 19] which undergoes nucleophilic addition/elimination and Liebeskind–Srogl cross-coupling reactions, and also for platform d bearing an 8-chloro group.…”

Exploring the Relationship between BODIPY Structure and Spectroscopic Properties to Design Fluorophores for Bioimaging

“…[5,7] Boron dipyrromethene (BODIPY)d yes are ideal to explore the relationship between structure and spectroscopic properties given their popular use in cellular imaging. BODIPY dyes combine desirable chemical, physical and spectroscopicp roperties [7][8][9][10][11] including chemicals tability,a bsorption maxima (l max ) aroundo ra bove 500 nm, sharp fluorescence emission and good quantum yields for the resulting fluorescence. [5,6,[12][13][14][15] Sharp excitation ande mission peakse nablep recise detection by confocal fluorescencem icroscopy.…”

A Modular Class of Fluorescent Difluoroboranes: Synthesis, Structure, Optical Properties, Theoretical Calculations and Applications for Biological Imaging

“…Fluorescent molecules have been of particulari nterest recently, and they have found applications in numerous fields, such as materials sciences, [1] laser dyes, [2] fluorescent switches, [3] chemosensors, [4] photodynamic therapy [5] and biological imaging. [6] Organoboron compoundsc onstitute ap opular class of fluorescent molecules, and the well-established boron-dipyrromethene (BODIPY)s eries is aw idely employed sub-class because of their excellento pticalp roperties, including their high quantum yields and their strong stabilityt op hysiological conditions.…”