Direct observation of guanine photo-oxidation from new potential anticancer drugs via ultrafast electron transfer

Abstract

In this study, we report an insight into the mechanism of interaction of three methyl-pyridinium derivatives with DNA and RNA, which intrigues us since the complexation is accompanied by a quite uncommon fluorescence quenching. A molecular mechanistic understanding was gained through the investigation of the photobehavior of these compounds in the presence of single nucleotides (ATP, CTP, GTP, and TTP) via advanced ultrafast spectroscopies. Our broadband fluorescence up-conversion results clearly highlighted the occurrence of a specific interaction with GTP, identified to be, through the femtosecond transient absorption experiments, an ultrafast electron transfer from guanine to methyl-pyridinium. Guanine photo-oxidation was directly observed in this work and interpreted to be at the root of photoinduced DNA and particularly RNA damage, and thus responsible for the toxicity exhibited by these new potential anticancer drugs toward tumor cells.