Norharmane, a naturally occurring photosensitizer: photooxidation of 2´-desoxyadenosine-5´-monophosphate

M. MICAELA GONZÁLEZ; FEDERICO A. O. RASSE-SURIANI; MATÍAS ALÉS-GANDOLFO; MARIANO FARACE; SANTIAGO ROLDAN; ROSA ERRA-BALSELLS; FRANCO M. CABRERIZO

Mendoza

Congreso; 21st I-APS (Inter-American Photochemical Society) Conference on Photochemistry; 2011

UV-A radiation (320-400 nm) induces damages to the DNA molecule and its components through photosensitized reactions. Norharmane is an alkaloid widespread in biological systems showing photosensitizing properties. Upon UV-A radiation, norharmane is able to induce chromosome damage in mammalian cells,[1] and/or to photoinduce DNA relaxation. Although these, the mechanisms involved in those processes are, to date, nevertheless still poorly understood. In the present work, we have studied the capability of norharmane to induce 2´-desoxyadenosine-5´-monophosphate (dAMP) photooxidation, in aqueous solution, upon UV-A excitation. The effect of pH was evaluated and the participation of reactive oxygen species (ROS), such as hydroxyl radical, superoxide anion and singlet oxygen was investigated. A strong dependence of the dAMP photosensitization on the pH was observed. The extent of the reaction was shown to be higher in the experiments performed at pH 4.7 than those performed at pH 10.2. Kinetic studies using ROS scavengers revealed that the chemical reactions between ROS and dAMP are not the main pathways responsible for dAMP photooxidation. Further analysis suggest that the predominant mechanism takes place, most probably, via electron transfer reactions (i.e., type I mechanism) from the single excited state (S1) of the protonated form of norharmane. In addition, the chemical nature of the photoproducts formed upon photosensitization was characterized by mass spectrometry (ESI-MS and UV-MALDI-TOF-MS). Reference: [1] K. Shimoi, H. Kawabata, I. Tomita, Mutat. Res., 1992, 268, 287. [2] M. M. Gonzalez, M. Pellon-Maison, M. A. Ales-Gandolfo, M. R. Gonzalez-Baró, R. Erra-Balsells, F. M. Cabrerizo, Org. Biomol. Chem., 2010, 8, 2543.