Spectroscopic, computational modeling and cytotoxicity of a series of meso-phenyl and meso-thienyl-BODIPYs

Abstract

A series of twenty-two BODIPY compounds were synthesized, containing various meso-phenyl and meso-thienyl groups, and their spectroscopic and structural properties were investigated using both experimental and computational methods. Further functionalization of the BODIPY framework via iodination at the 2,6-pyrrolic positions was explored in order to determine the effect of these heavy atoms on the photophysical and cytotoxicity of the meso-aryl-BODIPYs. BODIPYs bearing meso-thienyl substituents showed the largest red-shifted absorptions and emissions and reduced fluorescence quantum yields. The phototoxicity of the BODIPYs in human carcinoma HEp2 cells depends on both the presence of iodines and the nature of the meso-aryl groups. Six of the eleven 2,6-diiodo-BODIPYs investigated showed at least a sevenfold enhancement in phototoxicity (IC50 = 3.5–28 μM at 1.5 J/cm2) compared with the non-iodinated BODIPYs, while the others showed no cytotoxicity, while their singlet oxygen quantum yields ranged from 0.02 to 0.76. Among the series investigated, BODIPYs 2a and 4a bearing electron-donating meso-dimethoxyphenyl substituents showed the highest phototoxicity and dark/phototoxicity ratio, and are therefore the most promising for application in PDT.

Synthesis and Transformations of 5‐Chloro‐2,2′‐Dipyrrins and Their Boron Complexes, 8‐Chloro‐BODIPYs

“…However, the quantum yields for the meso -alkenyl, alkynyl, pyrrolyl, and thienyl-BODIPYs 20 – 25 were appreciably lower, particularly for 20 , the fluorescence of which was essentially quenched, due to the greater freedom of rotation for these smaller groups increasing the energy lost to non-radiative decay. [43] Boron substitution had no significant effect on the absorption and emission wavelengths, but did influence the fluorescence quantum yield. Although boron substitution with two methoxy groups significantly increased the quantum yield of BODIPY 15 ( Φ f =1.0) relative to 13 ( Φ f = 0.57), substitution with two ethyl groups reduced the quantum yield of BODIPY 12 ( Φ f =0.32) relative to 11 ( Φ f =0.83).…”

Synthesis and Reactivity of 4,4-Dialkoxy-BODIPYs: An Experimental and Computational Study

“…The product was purified by silica gel flash column chromatography using mixtures of petroleum ether and dichloromethane for elution. 34,43 General Procedure for O-BODIPYs using Method A. In an oven-dried flask, BODIPY (20.0 mg, 0.062 mmol) and NaOMe (21.0 mg, 0.389 mmol) were dissolved in anhydrous methanol (2 mL).…”

Synthesis, spectroscopic, and in vitro investigations of 2,6-diiodo-BODIPYs with PDT and bioimaging applications

“…Studies have shown that incorporation of iodines at the 2,6-positions of BODIPYs leads to enhanced intersystem crossing, whereas addition at the 3,5-positions promotes fluorescence [30]. In addition, phototoxicity depends on the substituents on the 2,6-diiodo-BODIPYs, and is favored by electron-donating 8-aryl groups [23–26]. …”

“…We have recently reported the synthesis and cytotoxicity properties of near-IR mono-and di-indolylstyryl-BODIPYs [38], and a series of 2,6-diiodo-BODIPYs [26]. Among these, the mono- indolylstyryl-BODIPYs showed high uptake by HEp2 cells with no detectable cytotoxicity in the absence or presense of light, while the 8-(3,5-dimethyoxyphenyl)-2,6-diiodo-1,3,5,7-tetramethyl-BODIPY ( 1 ) showed high phototoxicity (IC 50 = 4 µM at 1.5 J/cm 2 ) but remained non-toxic in the dark (IC 50 > 400 µM).…”