engleski

Photochemical formation of BODIPY-quinone methides: spectroscopic study and biological applications

Quinone methides (QMs) are reactive intermediates in the chemistry and photochemistry of phenols that have attracted scientific interest owing to their reactivity with DNA and proteins.[1] Moreover, some classes of anticancer antibiotics such as Mitomycin exhibit their antiproliferative activity due to metabolic formation of QMs that cross-link DNA. Consequently, simple QM precursors which generate QMs in photochemical reactions represent a potential class of compounds that could be developed as photoactivable drugs to treat cancer.[2] We have studied photochemical reactions of different classes of phenol molecules that undergo dehydration or deamination and deliver QMs, and investigated antiproliferative activity which QMs induce upon photogeneration.[2] Recently we have found an example of anthrol molecules that can be excited at 405 nm and deliver QMs, which exhibit selective cytotoxic effect on cancer stem cells.[3] However, for the real application in biology or medicine it is pivotal to develop new molecules that can be excited at wavelengths higher than 650 nm. Therefore, we have incorporated QM precursors to BODIPY chromophores.[4] Interestingly, investigation of photochemical reactivity of several classes of BODIPY-QM precursors indicated that they did not react in the singlet S1 state. However, we discovered that deamination and formation of QMs was achieved upon excitation to higher excited singlet states. Thus, photochemical reactivity of BODIPY compounds was investigated by preparative irradiations at shorter wavelengths and QMs were detected by laser flash photolysis. The experimental results were corroborated by computations which fully disclosed the reasons for the observed anti-Kasha photochemical reactivity. The applicability of BODIPY-QMs was investigated by MTT tests on several human cancer cell lines with and without the irradiation. Furthermore, we investigated the possibility to photochemically stain proteins with BODIPY fluorophores.

Anti-Kasha photochemistry ; BODIPY ; quinone methides ; fluorescent labeling

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