Covalently Mercurated 6-Phenylcarbazole Residues Promote Hybridization of Triplex-Forming Oligonucleotides.

Homothymidine DNA oligonucleotides bearing a 3'-terminal 6-phenyl-9H-carbazole C-nucleoside, mercurated at position 1, 8 or both, were synthesized and tested for their potential to form triple helices with homoadenine ⋅ homothymine duplexes. The monomercurated triplex-forming oligonucleotides favored hybridization with fully matched double helices and in some cases considerable increase of the melting temperature could be attributed to Hoogsteen-type Hg(II)-mediated interaction with the homoadenine strand. The dimercurated one, on the other hand, favored hybridization with double helices placing a homo mispair opposite to the carbazole residue, suggesting that simultaneous coordination of each of the two Hg(II) ions to a different strand is only possible in the absence of competition from Watson-Crick base pairing.

1,8-Dimercuri-6-Phenyl-1H-Carbazole as a Monofacial Dinuclear Organometallic Nucleobase.

A C-nucleoside with 6-phenyl-1H-carbazole as the base moiety has been synthesized and incorporated in the middle of an oligonucleotide. Mercuration of this modified residue at positions 1 and 8 gave the first example of an oligonucleotide featuring a monofacial dinuclear organometallic nucleobase. The dimercurated oligonucleotide formed stable duplexes with unmodified oligonucleotides placing either cytosine, guanine, or thymine opposite to the organometallic nucleobase.

2,6-Dimercuriphenol as a Bifacial Dinuclear Organometallic Nucleobase.

A C-nucleoside having 2,6-dimercuriphenol as the base moiety has been synthesized and incorporated into an oligonucleotide. NMR and UV melting experiments revealed the ability of this bifacial organometallic nucleobase surrogate to form stable dinuclear Hg -mediated base triples with adenine, cytosine, and thymine (or uracil) in solution as well as within a triple-helical oligonucleotide. A single Hg -mediated base triple between 2,6-dimercuriphenol and two thymines increased both Hoogsteen and Watson-Crick melting temperatures of a 15-mer pyrimidine⋅purine*pyrimidine triple helix by more than 10 °C relative to an unmodified triple helix of the same length.

Triplex Formation by Oligonucleotides Containing Organomercurated Base Moieties.

Homothymine oligonucleotides with a single 5-mercuricytosine or 5-mercuriuracil residue at their termini have been synthesized and their capacity to form triplexes has been examined with an extensive array of double-helical targets. UV and circular dichroism (CD) melting experiments revealed the formation and thermal denaturation of pyrimidine⋅purine*pyrimidine-type triple helices with all oligonucleotide combinations studied. Nearly all triplexes were destabilized upon mercuration of the 3'-terminal residue of the triplex-forming oligonucleotide, in all likelihood due to competing intramolecular Hg -mediated base pairing.