Release of free nucleobases from oligomers by copper(II)-peroxide adduct

The release of nucleobases from oligonucleotides (12-mer, d(5'-CGCTTTAAAGCG )(2), 8-mer, d(5'-AAACGTTT)(2), 7-mer, d(TCGCGCG)(2), and 6-mer, d(CGCGCG)( 2)) by copper(II) complex and hydrogen peroxide systems was investigated in terms of HPLC. The [Cu(bdpg)Cl]Cl complex gave a large quantity of free nu cleobases in the reaction mixture, but the activities of other compounds, s uch as [Cu(tpa)Cl]ClO4, were much lower than that of the (bdpg)-complex; wh ere (bdpg) and (tpa) represent a N,N-bis(2-pyridylmethyl) derivative of bet a -alanineamide and 2-aminomethylpyridine, respectively. The above results and the electrospray mass spectral data on the solutions strongly suggest t hat the remarkable activity of the (bdpg)-compound is due to the high elect rophilic nature of the copper(II)-hydroperoxide adduct, whose formation is greatly promoted through hydrogen bonding with the amide-oxygen atom coordi nated to the copper(II) atom, and this electrophilic copper(II)-peroxide ad duct attacks the sugar ring of nucleoside, to give the corresponding hydrox ylated species, and from which free nucleobases are released. (C) 2000 Else vier Science B.V. All rights reserved.