Silver(I)-mediated base pairing in DNA involving the artificial nucleobase 7,8-dihydro-8-oxo-1,N6-ethenoadenine

Isabell Schönrath; Vladimir B Tsvetkov; Miquel Barceló-Oliver; Marian Hebenbrock; Timofei S Zatsepin; Andrey V Aralov; Jens Müller

doi:10.1016/j.jinorgbio.2021.111369

Silver(I)-mediated base pairing in DNA involving the artificial nucleobase 7,8-dihydro-8-oxo-1,N⁶-ethenoadenine

J Inorg Biochem. 2021 Jun:219:111369. doi: 10.1016/j.jinorgbio.2021.111369. Epub 2021 Jan 27.

Authors

Isabell Schönrath¹, Vladimir B Tsvetkov², Miquel Barceló-Oliver³, Marian Hebenbrock¹, Timofei S Zatsepin⁴, Andrey V Aralov⁵, Jens Müller⁶

Affiliations

¹ Westfälische Wilhelms-Universität Münster, Institut für Anorganische und Analytische Chemie, Corrensstraße 28/30, 48149 Münster, Germany.
² World-Class Research Center "Digital biodesign and personalized healthcare", Sechenov First Moscow State Medical University, 8/2 Trubetskaya Str., 119146 Moscow, Russia; Research and Clinical Center for Physical Chemical Medicine, Malaya Pirogovskaya Str. 1a, 119435 Moscow, Russia.
³ Universitat de les Illes Balears, Departament de Química, carretera Valldemossa km 7.5, Ed. Mateu Orfila i Rotger, 07122 Palma de Mallorca, Spain.
⁴ Skolkovo Institute of Science and Technology, Bolshoy Boulevard 30, bld. 1, 121205 Moscow, Russia; Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory Str. 1-3, 119992 Moscow, Russia.
⁵ Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya Str. 16/10, 117997 Moscow, Russia. Electronic address: baruh238@mail.ru.
⁶ Westfälische Wilhelms-Universität Münster, Institut für Anorganische und Analytische Chemie, Corrensstraße 28/30, 48149 Münster, Germany. Electronic address: mueller.j@uni-muenster.de.

PMID: 33878529
DOI: 10.1016/j.jinorgbio.2021.111369

Abstract

The artificial nucleobase 7,8-dihydro-8-oxo-1,N⁶-ethenoadenine (X) was investigated with respect to its ability to engage in Ag(I)-mediated base pairing in DNA. Spectroscopic data indicate the formation of dinuclear X-Ag(I)₂-X homo base pairs and mononuclear X-Ag(I)-C base pairs (C, cytosine). Density functional theory calculations and molecular dynamics simulations indicate that the nucleobase changes from its lactam tautomeric form prior to the formation of the Ag(I)-mediated base pair to the lactim form after the incorporation of the Ag(I) ions. Fluorescence spectroscopy indicates that the two Ag(I) ions of the homo base pair are incorporated sequentially. Isothermal titration calorimetry confirms that the affinity of one of the Ag(I) ions is about tenfold higher than that of the other Ag(I) ion. The computational analysis by means of density functional theory confirms a much larger reaction energy for the incorporation of the first Ag(I) ion. The thermal stabilization upon the formation of the dinuclear Ag(I)-mediated homo base pair exceeds the one previously observed for the closely related nucleobase 1,N⁶-ethenoadenine by far, despite very similar structures. This additional stabilization may stem from the presence of water molecules engaged in hydrogen bonding with the additional oxygen atom of the artificial nucleobase X. The highly stabilizing Ag(I)-mediated base pair is a valuable addition to established dinuclear metal-mediated base pairs.

Keywords: 7,8-dihydro-8-oxo-1,N(6)-ethenoadenine; DNA; Isothermal titration calorimetry; Metal-mediated base pair; Nucleic acid; Silver.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenine / analogs & derivatives*
Adenine / chemistry
Base Pairing*
Calorimetry / methods
Circular Dichroism / methods
Cytosine / chemistry
DNA / chemistry*
Hydrogen Bonding
Ions / chemistry
Molecular Structure
Nucleic Acids / chemistry
Oligonucleotides / chemistry
Oxygen / chemistry
Silver / chemistry*
Spectrometry, Fluorescence / methods
Transition Temperature

Substances

Ions
Nucleic Acids
Oligonucleotides
1,N(6)-ethenoadenine
Silver
Cytosine
DNA
Adenine
Oxygen