Synthesis, spectroscopic properties and cytotoxicity of boron- dipyrromethene fluorescent dyes

Abstract

In this study, we report the synthesis of three quinolone bearing imidazole derivatives 2, 3 and 4 and two quinolone bearing BODIPY dyes 5 and 7. In the synthesis of 2, 3 and 4, the first step was the preparation of the starting compound 2-chloro-3-formyl quinoline (1); the Vilsmeier-Haack cyclisation protocol was used. Compound 1 was used with the appropriate diamine, together with POCl3 to produce 2, 3 and 4. These compounds were characterized by IR, 1H-NMR and 13C-NMR. In the synthesis of 5, compound 1 was used whilst 6 was used for the synthesis of 7. This was via. a one-pot synthesis using conventional reflux apparatus and Schlenk technique. These compounds were characterized by IR, 1H-NMR and 13C-NMR. Four other BODIPY dyes were also synthesized but their purification by column chromatography were unsuccessful. However a HPLC method was developed using 2 as a model; the best eluting solvent was 65 % methanol. After synthesis, 2, 3, 4, 5 and 7 were used for spectroscopic studies by UV-visible and fluorescence spectroscopy. In the UV-visible studies, 2, 3 and 4 were dissolved, separately, in five solvent viz. ethanol, methanol, dichloromethane, chloroform and acetonitrile. The UV profile of each compound was obtained and the maximum absorbance was then used for fluorescence studies. In the fluorescence studies, all the compounds displayed a fluorescence nature when excited with the various wavelengths. The fluorescence properties, namely Stoke shift, quantum yield, life time, molar absorptivity and brightness, were investigated to establish the properties of each compound in all five solvent systems. The Stoke shift was evident in all compounds and the quantum yields were below one which indicates no other electron transfer mechanisms occurring. The results displayed a favorable response and this further lead to analysis of the synthesized compounds for it potential application as a chemosensor. Eight metal ions were used to investigate this property. All eight metal ions, when reacted with the synthesized compounds, as ligands, showed chemosensor properties, viz. photon induced electron transfer, inter-molecular charge transfer and fluorescence resonance electron transfer, as a quenching and enhancement of emission and excitation peaks were observed. The compounds were further investigated for its potential for its use as a photovoltaic cells. The energies of the compounds were obtained from the analyses of the reflectance and transmission spectra. It was found that the synthesized compounds displayed properties which were positive for its use as a photovoltaic cell. Biological analyses using molecular docking analyses and MTT assays were conducted to determine the use of these as an anti-cancer drug. Compounds 2 and 3 formed hydrogen bonds with GLU 25 and LEU 27, respectively with MDM2-p53 proteins. Following the molecular docking studies, the MTT assay was performed on all five synthesized compounds. The BODIPYs with the quinoline moieties demonstrated a reduction in the rate of A549 cell proliferation when compared to the imidazole and benzimidazoles; this was observed for compounds 5 and 7. Further, a comparison between imidazoles clearly shows that compounds 3 and 4 also decreased cell proliferation. In contrast compound 2 exhibited an increased rate of cell proliferation. The optical density of the control cell, is much higher that the plates for concentration 31.25 µg/ mL to 500 µg/ mL. However 2 cannot be discarded; this compound clearly shows that it possesses anti-hyperglycaemic properties and further studies are recommended.