Syntheses of nucleic acid mimics designed for metal-induced strand formation on DNA

Abstract

This paper describes design and syntheses of a new class of chelator-type nucleic acid mimics. Four nucleic acid mimics 7 , 11 , 15 , 17 possess a nucleobase and two ethylenediamine moieties for intermolecular metal coordination. We expected that chelator-type nucleic acid mimics formed a strand in the presence of metal ion and then interacted with a single-stranded DNA. Efficient synthetic routes leading to the four nucleic acid analogues have been achieved via the key intermediate compound 5 which was derived from 3,5-dimethylphenol in five steps. Compound 7 was treated with zinc nitrate and Zn complex 8 was isolated as crystals. 1H NMR study of Zn complex 8 in D 2O showed the single-strand formation. Job plots showed that mixture of (dT) 70 with Zn complex 8 at 5°C reached a minimum absorbance at a mole ratio of 2:1, and the hypochromic effect showed the π–π stacking interaction between the nucleobases. Thermal denaturation study at 2:1 mole ratio of complexes between (dT) 70 and Zn complex 8 showed melting point at 27°C.