2,6‐Dimercuriphenol as a Bifacial Dinuclear Organometallic Nucleobase

Abstract

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 HgII‐mediated base triples with adenine, cytosine, and thymine (or uracil) in solution as well as within a triple‐helical oligonucleotide. A single HgII‐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. This novel binding mode could be exploited in targeting certain pathogenic nucleic acids as well as in DNA nanotechnology.

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

“…[5] Inspired by these results,wereport herein the synthesis and hybridization studies of an oligonucleotide incorporating a1 ,8-dimercury-6-phenyl-1H-carbazole residue as the first example of ac ovalently metallated oligonucleotide with the potentialf or dinuclear metal-mediated base pairing. Unlike the previously reported 2,6-dimercuriphenol, [6] 1,8-dimercury-6-phenyl-1H-carbazole is monofacial, with the two Hg II ions bondedonthe same side of the carbazole base. With unsubstituted 1H-carbazole, mercuration should take place exclusively ortho and para to the NH group (a strongly activating ortho/ para director) and two of the ortho carbons are bonded two each other,l eaving only two ortho and two para carbons available for mercuration.…”

“…Heck coupling between compound 3 and {(2 R ,3 S )‐3‐[( tert ‐butyldimethylsilyl)oxy]‐2,3‐dihydrofuran‐2‐yl}methanol afforded the ketone intermediate 4 exclusively as the β anomer. Assignment of the absolute configuration at the anomeric carbon was based on comparison of the NMR spectra with those of similar compounds reported previously . The tert ‐butyldimethylsilyl protection of the secondary hydroxy group of the sugar moiety was also quantitatively removed during the Heck coupling.…”

“…[7] Heck coupling between compound 3 and {(2R,3S)-3-[(tert-butyldimethylsilyl)oxy]-2,3-dihydrofuran-2-yl}methanol afforded the ketone intermediate 4 exclusively as the b anomer.A ssignment of the absolutec onfiguration at the anomeric carbon was based on comparison of the NMR spectra with those of similar compounds reported previously. [6,8] The tert-butyldimethylsilyl protection of the secondary hydroxy group of the sugar moiety wasa lso quantitatively removed during the Heck coupling. Reduction of compound 4 gave the 6-bromo-1H-carbazole C-nucleoside 5 and subsequentS uzuki-Miyaura coupling with phenylboronic acid the 6-phenyl-1H-carbazole C-nucleoside 1.F inally,t he 5'-hydroxy group of compound 1 was protected as ad imethoxytrityl ether and the 3'-hydroxy group of the resulting intermediate 6 phosphitylatedt oa fford the phosphoramiditeb uilding block 2.…”

Metal‐Modified Nucleic Acids: Metal‐Mediated Base Pairs, Triples, and Tetrads

“…[43] In as imilar approach, the dinuclear organometallic nucleobase 2,6-dimercuriphenol Hg F Hg was introduced recently. [44] It is capable of forming highly stabilizing metalmediated base triples with av ariety of natural nucleobases, including adenine,c ytosine and most prominently thymine. Figure 5a depicts the proposed structure of the T-Hg F Hg -T base triple.I nterestingly,b oth dissociation steps (triplex !…”

“…Metal-stabilized triplex formation has been proposed to be relevant for the specific targeting of nucleic acid duplexes. [44,45] In analogy to metal-mediated base pairs formed from canonical nucleobases,o ne Ag I -stabilized base triple involving guanine and cytosine has been reported. Conceptually,the C-Ag I -G:C triple (Figure 5b)i sc omposed of aC -Ag I -G Hoogsteen base pair and aG:C Watson-Crick base pair.…”