Supramolecular Approach to Enantioselective DNA Recognition Using Enantiomerically Resolved Cationic 4-Amino-1,8-naphthalimide-Based Tr枚ger鈥檚 Bases
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- 作者：Swagata Banerjee ; Sandra A. Bright ; Jayden A. Smith ; Jeremy Burgeat ; Miguel Martinez-Calvo ; D. Clive Williams ; John M. Kelly ; Thorfinnur Gunnlaugsson
- 刊名：Journal of Organic Chemistry
- 出版年：2014
- 出版时间：October 3, 2014
- 年：2014
- 卷：79
- 期：19
- 页码：9272-9283
- 全文大小：612K
- ISSN：1520-6904
文摘
The synthesis and photophysical studies of two cationic Tr枚ger鈥檚 base (TB)-derived bis-naphthalimides 1 and 2 and the TB derivative 6, characterized by X-ray crystallography, are presented. The enantiomers of 1 and 2 are separated by cation-exchange chromatography on Sephadex C25 using sodium (鈭?-dibenzoyl-l-tartarate as the chiral mobile phase. The binding of enantiomers with salmon testes (st)-DNA and synthetic polynucleotides are studied by a variety of spectroscopic methods including UV/vis absorbance, circular dichroism, linear dichroism, and ethidium bromide displacement assays, which demonstrated binding of these compounds to the DNA grooves with very high affinity (K 鈭?106 M鈥?) and preferential binding of (鈭?-enantiomer. In all cases, binding to DNA resulted in a significant stabilization of the double-helical structure of DNA against thermal denaturation. Compound (卤)-2 and its enantiomers possessed significantly higher binding affinity for double-stranded DNA compared to 1, possibly due to the presence of the methyl group, which allows favorable hydrophobic and van der Waals interactions with DNA. The TB derivatives exhibited marked preference for AT rich sequences, where the binding affinities follow the order (鈭?-enantiomer > (卤) > (+)-enantiomer. The compounds exhibited significant photocleavage of plasmid DNA upon visible light irradiation and are rapidly internalized into malignant cell lines.