Metal-mediated base pairing in DNA involving the artificial nucleobase imidazole-4-carboxylate

Abstract The use of imidazole-4-carboxylate ( X ) as an artificial nucleobase in metal-mediated base pairing is reported. Towards this end, the corresponding deoxyribonucleoside was synthesized and structurally characterized as its sodium salt (sodium 1,2-dideoxy-1-(4-carboxyimidazol-1-yl)- d -ribofuranose). The deoxyribonucleoside was incorporated into different DNA duplexes (parallel-stranded and antiparallel-stranded), and their Cu(II)- and Ag(I)-binding behavior was investigated. It was shown that both X –Cu(II)– X and X –Ag(I)– X base pairs can be formed, with the former being more stabilizing than the latter. The formation of an X –Cu(II)– X base pair is accompanied by an increase in the duplex melting temperature of approximately 20 °C for antiparallel-stranded duplexes and of 12 °C for the parallel-stranded duplex under investigation. Imidazole-4-carboxylate represents the first imidazole-based nucleoside for Cu(II)-mediated base pairing. Moreover, it is the smallest nucleoside known to form stable Cu(II)-mediated base pairs. Structures of the X –Cu(II)– X and X –Ag(I)– X base pairs are proposed, too, based on molecular structures obtained using the model nucleobase 1-benzyl-1 H -imidazole-4-carboxylate.