Oligonucleotides Featuring a Covalently Mercurated 6‐Phenylcarbazole Residue as High‐Affinity Hybridization Probes for Thiopyrimidine‐Containing Sequences. Issue 69 (19th October 2022)

• Record Type: Journal Article
• Authors: Kotammagari, Tharun K.; Tähtinen, Petri; Lönnberg, Tuomas
• Is Part Of: Chemistry. Volume 28:Issue 69(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-10-19
• Subjects: base pairs -- hybridization -- mercury -- oligonucleotides -- thionucleosides; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202202530
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: Short oligonucleotides incorporating either 1‐mercuri‐6‐phenylcarbazole, 8‐mercuri‐6‐phenylcarbazole, or 1, 8‐dimercuri‐6‐phenylcarbazole C‐nucleoside in the middle of the chain have been synthesized and studied for their potential as hybridization probes for sequences containing thiopyrimidine nucleobases. All of these oligonucleotides formed very stable duplexes with complementary sequences pairing the organometallic moiety with either 2‐ or 4‐thiothymine. The isomeric monomercurated oligonucleotides were also able to discriminate between 2‐ and 4‐thiothymine based on the different melting temperatures of the respective duplexes. DFT‐optimized structures of the most stable mononuclear Hg II ‐mediated base pairs featured a coordinated covalent bond between Hg II and either S2 or S4 and a hydrogen bond between the carbazole nitrogen and N3. The dinuclear Hg II ‐mediated base pairs, in turn, were geometrically very similar to the one previously reported to form between 1, 8‐dimercuri‐6‐phenylcarbazole and thymine and had one Hg II ion coordinated to a thio and the other one to an oxo substituent. Abstract : Getting back to (nucleo)base : Oligonucleotides incorporating a central 1‐ or 8‐mercuri‐6‐phenyl‐1 H ‐carbazole residue show great promise as high‐affinity hybridization probes, discriminating between all canonical nucleobases as well as 2‐ and 4‐thiothymines by melting temperature margins of at least 5 °C. Duplexes facilitating Hg II −S coordination were particularly stable, with melting temperatures nearly 30 °C higher than those of respective unmodified duplexes.