Naslov
Characterization of sterically congested biphenyl quinone methides and zwitterions by laser flash photolysis, and investigation of their antiproliferative activity

Autori
Basarić, Nikola ; Bobinac, Damir ; Cindro, Nikola ; Mlinarić-Majerski, Kata ; Uzelac, Lidija ; Kralj, Marijeta ; Wan, Peter

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
XXV International Conference on Photochemistry (ICP 2011) : abstracts / - Peking, 2011, 166-116

Skup
International Conference on Photochemistry (25 ; 2011)

Mjesto i datum
Peking, Kina, 07.08.2011. - 12.08.2011

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
ESIPT reactions; Quinone methides; zwitterions; antiproliferative effect

Sažetak
Quinone methides (QM) are common intermediates in the chemistry and photochemistry of phenols.(1) Scientific interest in QM chemistry was sparked two decades ago due to a discovery of their potential biological activity. Now it is well accepted that QMs alkylate DNA and act as DNA cross-linking agents.(2) Moreover, antiproliferative activity of some antibiotics is based on metabolic formation of QMs and alkylation of DNA. In cooperation with Wan's group, who are interested in acid-base photochemistry and characterization of QMs formed in excited state proton transfer reactions, (3) we prepared a special class of sterically congested phenols that give QMs in photochemical dehydration reactions.(4) Incorporation of a bulky adamantyl group to the methylene position of these QMs prolonged their lifetimes and increased selectivity in the reaction with nucleophiles. In continuation of the research on congested QMs we have become interested in biphenyl QM derivatives and their potential applicability as antiproliferative agents. We found out that irradiation of 2-hydroxyadamantyl derivatives of 2-phenylphenols give rise to two photochemical S1 pathways: excited state intramolecular proton transfer (ESIPT) and photodehydration, both delivering QMs.(5) QMs formed by photodehydration were characterized by LFP, whereas QMs formed in the ESIPT reactions were short-lived and could not be detected in the nanosecond time-scale. Herein we present photochemistry of sterically congested 3-phenylphenols and 4-phenylphenols giving rise to biphenly QMs 1 and 2, and zwitterions 3-6. The phenols were photolyzed in aqueous solvent in the presence of different nucleophiles to characterize the nucleophilic addition products to QMs. Singlet excited states of phenols were characterized by steady-state and time-resolved fluorescence, and LFP was performed to characterize QMs. In vitro antiproliferative studies were conducted on three cancer cell lines in the presence of the phenols, with and without the irradiation, to investigate if photochemical generation of QMs leads to antiproliferative effect.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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