Synthesis of nucleosides and dNTPs bearing oligopyridine ligands linked through an octadiyne tether, their incorporation into DNA and complexation with transition metal cations

Abstract

Modified nucleosides (dA^Rs and dC^Rs) bearing bipyridine or terpyridine ligands attached through an octadiyne linker were prepared by single-step aqueous-phase Sonogashira cross-coupling of 7-iodo-7-deaza-2′-deoxyadenosine and 5-iodo-2′-deoxycytidine with the corresponding bipyridine- or terpyridine-octadiynes and were triphosphorylated to the corresponding nucleoside triphosphates (dA^RTPs and dC^RTPs). The modified dN^RTPs were successfully incorporated into the oligonucleotides by primer extension experiment (PEX) using different DNA polymerases and the PEX products were used for post-synthetic complexation with divalent metal cations. The complexation of these DNAs containing flexibly-tethered ligands was compared with the previously reported ones bearing rigid acetylene-linked ligands suggesting the possible formation of both inter- and intra-strand complexes with Ni²⁺ or Fe²⁺.