Synthesis of 5-(2,2′-Bipyridinyl and 2,2′-Bipyridinediiumyl)-2′-Deoxyuridine Nucleosides: Precursors to Metallo-Dna Conjugates

Abstract

The synthesis of 2,2'-bipyridinyl-2'-deoxyuridine metal-chelator nucleosides (Bipy-dU) with either ethynyl or ethylenyl linkers was now been accomplished. These new nucleosides will permit the construction of a number of corresponding metallo-DNA conjugates where many types of metals can be complexed to the 2,2'-bipyridinyl chelator group and the resulting metallo-dU conjugates incorporated into DNA oligonucleotides. Additionally this paper also reports the synthesis of a di-N-alkylated bipyridinediiumyl-2'-deoxyuridine nucleoside (Bipy(2+)-dU) with an ethylenyl linker. The Bipy(2+)-dU nucleoside was found to decompose under basic conditions precluding its use in standard automated DNA-synthesis by the phosphoramidite method. No such restrictions apply to the two Bipy-dU nucleosides reported here for use as metal chelators.

Synthesis of 5-(Pyridinyl and Pyridiniumyl)-2′-Deoxyuridine Nucleosides: Reversible Electron Traps for Dna

“…Even for the case of hole transport in DNA duplexes at room temperature there are only a small number of direct observations of elementary electron transfer reactions and no direct observations of the dynamics of hole transport. [46] As will be discussed below, bipyridinediiumyl-dU nucleosides are base sensitive, but pyridiniumyl-dU nucleosides are not. To this end we sought to link pyridines to 2 0 -deoxyuridine (pyridinyl-dU) and then to convert these new conjugates into pyridiniumyl-dU nucleosides.…”

Photoinduced short-range electron transfer in DNA with fluorescent DNA bases: lessons from ethidium and thiazole orange as charge donors

“…75 However, methyl viologen cannot be synthetically incorporated into oligonucleotides using the corresponding phosphoramidite as a DNA building block due to its instability during the strong basic conditions that are typically used for DNA workup. 76 However, the ''click'' chemistry allows the postsynthetic modification of oligonucleotides that were presynthesized and modified by an alkyne group. 77 Using the methyl viologensubstituted propyl azide, 78 and the protocol for the Cu(I)catalyzed ''click'' modification 77 we were able to prepare the corresponding modified DNA2a (see ESIw).…”

A Facile and Inexpensive Synthesis of 6-Ethynylbipyridine

“…The syntheses of functionalized 2,2'-bipyridines for the above areas are therefore needed and although numerous methods exist in the literature inexpensive and facile procedures are desirable. One such bipyridine is 6-ethynylbipyridine (1), which has the ability to undergo Sonogashira coupling to a host of other materials and has therefore been used in the synthesis of metallo-DNA conjugates [1], nucleosides bearing metal complexes for antiviral activity [2][3][4] and photoactive materials [5][6][7][8]. The reported synthesis [1] (Scheme 1) relies on a Stille reaction in the first step for the formation of 6-bromo-2,2'-bipyridine (a Suzuki coupling has also been reported in 54% yield [9]), which, in a second step, undergoes further coupling of the resulting bromobipyridine product with the expensive trimethylacetylene (TMSA).…”