Synthesis and DNA cleavage activity of triazacrown-anthraquinone conjugatesElectronic supplementary information (ESI) available: Spectra for all new compounds, agarose gel electrophoretogram and kinetic data. See DOI: 10.1039/c0nj00347f

• Main Authors: Xu, Weihong, Yang, Xiaoli, Yang, Lian, Jia, Zhao-Li, Wei, Li, Liu, Fang, Lu, Guo-Yuan
• Format: Journal Article
• Language: English
• Published: 01.11.2010
• ISSN: 1144-0546; 1369-9261
• DOI: 10.1039/c0nj00347f

1,4,7-Triazacyclononane (TACN), with DNA cleaving ability, was appended to anthraquinone via different spacers to construct the new compounds 1,8-[2,2′-(1,4,7-triazacyclonon)diethoxy] anthracene-9,10-dione hydrochloride ( 1 ) and 1,8-[2,2′-(1,4,7-triazacyclonon)dihexyloxy] anthracene-9,10-dione hydrochloride ( 2 ) as new agents for metal-free DNA cleavage. Fluorescence and CD spectroscopic studies suggest an intercalating DNA binding mode, and the apparent DNA binding constants of 1 and 2 are 3.93 × 10 7 and 6.07 × 10 7 M −1 , respectively. Compound 2 , bearing the longer spacer, exhibits the higher DNA binding ability. The apparent initial first-order rate constant ( k obs ) of DNA cleavage promoted by 1 and 2 (0.05 mM) in physiological media are 0.077 ± 0.0028 and 0.123 ± 0.0027 h −1 , respectively. The 51-fold and 82-fold rate accelerations over parent TACN (the k obs is 0.0015 ± 0.00003 h −1 (0.05 mM) under the same conditions) are due to the anthraquinone moiety of compounds 1 and 2 intercalating into the DNA base pairs via stacking interactions. ESI-MS analysis of the dinucleotide cleavage promoted by 1 and 2 , and radical scavenger inhibition studies suggest that the cleavage process is a hydrolytic mechanism. Two triazacrown-anthraquinone conjugates were synthesized as new metal-free DNA cleaving reagents, and their cleavage efficiency, interactions with DNA were studied by spectroscopic techniques and agarose gel electrophoresis.