Design, Synthesis, and Characterization of 1-(Anthracen-9-ylmethyl)-1,5,9-triazacyclododecane (Ant-[12]aneN3) and Its DNA Photocleavage Activity

Abstract

Here, a DNA cleavage reagent (1-(anthracen-9-ylmethyl)-1,5,9-triazacyclododecane = Ant-[12]aneN3) was designed and synthesized, and its DNA photocleavage activity under UV irradiation at λ = 365 nm was evaluated. Ant-[12]aneN3 is a molecule containing anthracene as the photosensitizer and [12]aneN3 ( = 1,5,9-triazacyclododecane) as the DNA-interacting component. The cyclic polyamine [12]aneN3 could coordinate with zinc ions (Zn^II) and affect DNA cleavage activity. Therefore, when Ant-[12]aneN3 reacted with Zn(NO₃)‧6H₂O, the product was not a Zn^II complex but an N-protonated form of Ant-[12]aneN3. In DNA cleavage experiments with the pUC19 plasmid, Ant-[12]aneN3 also showed DNA photocleavage activity in a Zn^II-independent manner. That is, [12]aneN3 enhances the DNA photocleavage activity of anthracene in a Zn^II-independent manner, unlike bpa (bis(2-picolyl)amine), which was previously reported to enhance DNA cleavage activity by chelating Zn^II. Under physiological conditions, the nitrogen atoms of [12]aneN3 appear protonated without the addition of Zn^II salts and showed an affinity for the negatively charged DNA. The results of this study may facilitate the design of effective DNA cleavage reagents.