Synthesis of water‐soluble BODIPY dyes and investigation of their DNA interaction properties and cytotoxicity/phototoxicity

Abstract

In this study, water‐soluble BODIPY dyes (BDPY‐4, BDPY‐5) bearing dimethylamino and diethylamino groups were synthesized for the first time. The DNA interaction and nuclease effect of two water‐soluble BODIPY dyes were examined using absorption, competitive binding experiments, and agarose gel electrophoresis. Then, cytotoxicity and phototoxicity of the compounds were determined against A549 cells by MTT cell viability assay. The ultraviolet–visible (UV–vis) spectra of BDPY‐4 and BDPY‐5 displayed hypochromism and absorption maxima shifted to the red region. In addition, Kb values of the compounds were calculated as 2.23 × 104 and 4.84 × 104 M−1, respectively. An high‐performance liquid chromatography (HPLC) instrument without a column was used to conduct competitive binding experiments for the first time. The approach prevented the decrease in the response due to dilution and enabled the analysis to be carried out in a short time. Upon increasing concentrations of the compounds, the emission intensity of EB‐DNA significantly decreased. These obtained results suggested that the compounds bound to CT‐DNA with intercalative mode. At the same time, the Stern–Volmer constants were determined as 1.80 × 106 and 1.79 × 106 M−1 for BDPY‐4 and BDPY‐5, respectively, which is coherent with intercalative binding mode. The compounds did not display noticeable photonuclease actions with light irradiation. BDPY‐4 and BDPY‐5 showed moderate phototoxic properties on light irradiation.

Photocaged DNA-Binding Photosensitizer Enables Photocontrol of Nuclear Entry for Dual-Targeted Photodynamic Therapy

“…The binding constants ( K D ) for BB-1 and BB-2 to CT-DNA were ∼6 and 10 μM, respectively, comparable to Br-DAPI ( K D ∼19 μM). We hypothesize the stronger binding to DNA with BB compounds compared to free Br-DAPI is due to the planar conjugated structure of WinterGreen’s BODIPY core, capable of intercalating with DNA base pairs as previously observed with BODIPY dyes modified with cationic groups. − To test for WinterGreen’s interaction with CT-DNA, we monitored the primary region of WinterGreen photocage’s absorption spectrum (400–700 nm) in BB-1 (20 μM) upon titration of CT-DNA (Figure S3). A decrease as well as a redshift in its absorption spectrum was observed, which is expected for DNA-binding BODIPY compounds .…”