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

Abstract

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. A highly stabilizing (ΔTm=7.3 °C) HgII‐mediated base pair was formed with thymine. According to DFT calculations performed at the PBE0DH level of theory, this base pair is most likely dinuclear, with the two HgII ions coordinated to O2 and O4 of the thymine base.

Organomercury Nucleic Acids: Past, Present and Future

“…NMR spectrometric or X-ray crystallographic data on such base pairs is not available but high-level DFT calculations have predicted remarkably similar structures for two dinuclear Hg IImediated base pairs with thymine, one coordinative (Figure 3A) [90,91] and one organometallic (Figure 3B). [10] In both of these base pairs, the two Hg II ions coordinate to O2 and O4 of the thymine base. With the coordinative 1,N 6 -ethenoadenine-Hg II 2 -thymine base pair, more recent calculations suggest additional coordination to thymine N3 when this base pair is embedded within the base stack of a double helix.…”

“…Facile and selective mercuration at C2 of a 3‐fluoro‐6‐methylaniline C‐nucleoside (Figure 1H) provides an illustrative example of the power of this approach [8] . Nucleobase analogues with multiple electron‐rich carbon atoms, such as phenol [9] or 6‐phenyl‐1 H ‐carbazole [10] (Figure 1I and J), can be mercurated more than once although at progressively slower rates.…”

“…Multinuclear organomercury nucleobases can be categorised as mono‐ or bifacial depending on the positioning of the Hg II ions relative to each other. In monofacial bases, such as 1,8‐dimercuri‐6‐phenyl‐1 H ‐carbazole, [10] the Hg II bridges converge to bind to a single nucleobase, typically on its Watson–Crick face. NMR spectrometric or X‐ray crystallographic data on such base pairs is not available but high‐level DFT calculations have predicted remarkably similar structures for two dinuclear Hg II ‐mediated base pairs with thymine, one coordinative (Figure 3A) [90,91] and one organometallic (Figure 3B) [10] .…”

“…In monofacial bases, such as 1,8‐dimercuri‐6‐phenyl‐1 H ‐carbazole, [10] the Hg II bridges converge to bind to a single nucleobase, typically on its Watson–Crick face. NMR spectrometric or X‐ray crystallographic data on such base pairs is not available but high‐level DFT calculations have predicted remarkably similar structures for two dinuclear Hg II ‐mediated base pairs with thymine, one coordinative (Figure 3A) [90,91] and one organometallic (Figure 3B) [10] . In both of these base pairs, the two Hg II ions coordinate to O2 and O4 of the thymine base.…”

“…With the coordinative 1, N 6 ‐ethenoadenine‐Hg II 2 ‐thymine base pair, more recent calculations suggest additional coordination to thymine N3 when this base pair is embedded within the base stack of a double helix [91] . While very high stabilities have been reported for a number of multinuclear Ag I ‐mediated base pairs, [92–98] corresponding results on these dinuclear Hg II ‐mediated base pairs (organometallic or otherwise) were less impressive, [10,90] perhaps owing to electrostatic repulsion between the Hg II ions.…”