engleski

Synthesis of photochemically reactive BODIPY compounds with potential application for cancer treatment

One approach to the treatment of cancer is based on the use of light. Specifically, the so-called photodynamic therapy relies on the use of photosensitizers that absorb light and transfer the absorbed energy to oxygen to generate singlet oxygen and other reactive species responsible for cytotoxic effects. However, cancer cells are often hypoxic, making this approach ineffective. As a solution to this problem, we designed a series of molecules that are non-toxic but, after exposure to light in a photochemical reaction, produce cytotoxic species, quinone-methides (QM). QMs are important intermediates in the chemistry of phenols, known for their biological activity due to reactivity with biologically relevant molecules such as DNA and proteins. This work describes the derivatization of a fluorescent BODIPY dye into a QM precursor. The application of fluorescent dyes in biological systems has been extensively researched, with particular attention given to fluorescent markers for fluorescence spectroscopy and microscopy. Furthermore, BODIPY compounds are particularly interesting due to their exceptional photophysical properties that can be easily modified by synthetic modifications. In this study, the synthesis of a new QM precursor with a significantly shifted absorption towards the red part of the electromagnetic spectrum is described as a consequence of extended conjugation of the BODIPY chromophore with an ethynylphenol group. The photophysical properties of the synthesized dye were investigated using UV-Vis and steady-state and time-resolved fluorescence spectroscopy. The photochemical reactivity of the dye was examined by illumination in methanol, and HPLC analysis detected methanol adducts, confirming the expected QMs as intermediates in the reactions. The obtained results are particularly interesting because the investigated dye exhibits unusual anti-Kasha photochemical reactivity. Specifically, reactions occur only upon excitation to higher excited singlet states, while excitation to S1 leads only to fluorescence deactivation. Consequently, the newly synthesized molecules have the potential for development into photoactivatable fluorescent markers for various biologically important molecules such as proteins and DNA.

BODIPY; fluorescence; quinone-methides; photochemistry; photophysics

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