Stable Hg(II)-mediated base pairs with a phenanthroline-derived nucleobase surrogate in antiparallel-stranded DNA

Biswarup Jash,Jens Müller

doi:10.1007/s00775-020-01788-x

Biswarup Jash, Jens Müller

Open Access

https://doi.org/10.1007/s00775-020-01788-x

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Abstract

Metal-mediated base pairs involving artificial nucleobases have emerged as a promising means for the site-specific functionalization of nucleic acids with metal ions. In this context, a GNA-appended (GNA: glycol nucleic acid) nucleoside analogue containing the artificial nucleobase 1H-imidazo[4,5-f][1,10]phenanthroline (P) has already been applied successfully in a variety of homo- and heteroleptic metal-mediated base pairs, mainly involving Ag(I) ions. Herein, we report a thorough investigation of the Hg(II)-binding properties of P when incorporated into antiparallel-stranded DNA duplexes. The artificial nucleobase P is able to form Hg(II)-mediated homoleptic base pairs of the type P–Hg(II)–P with a [2 + 2] coordination environment. In addition, the heteroleptic P–Hg(II)–T pair was investigated. The addition of a stoichiometric amount of Hg(II) to a duplex comprising either a P:P pair or a P:T pair stabilizes the DNA duplex by 4.3 °C and 14.5 °C, respectively. The P–Hg(II)–T base pair, hence, represents the most stabilizing non-organometallic Hg(II)-mediated base pair reported to date. The formation of the Hg(II)-mediated base pairs was investigated by means of temperature-dependent UV spectroscopy and CD spectroscopy.Graphic abstract

Highlights

Natural DNA is composed of four nucleobases and an anionic sugar-phosphate backbone
We have previously reported the use of the artificial nucleoside analogue P in various contexts of metal-mediated base pairing [47,48,49,50], both in antiparallel- and parallel-stranded DNA duplexes (Fig. 1b)
The metal-binding ability of P inside antiparallel-stranded DNA duplexes was investigated in the context of both homo- and hetero-base pairs by introducing P as a central nucleoside surrogate into two short oligonucleotide sequences (Table 1)

Summary

Introduction

Natural DNA is composed of four nucleobases and an anionic sugar-phosphate backbone. The concept of applying nucleobases as ligands to locate metal ions inside a DNA duplex is nowadays referred to as metal-mediated base pairing In such artificial base pairs, the natural hydrogen bonds between the complementary bases are formally replaced by metal–ligand coordinate bonds [9], leading to the desired site-specific functionalization. Research on metal-mediated base pairing has not been restricted to natural nucleobases It has rather been expanded by the introduction of artificial ligand-based nucleosides to bring in diversity in the form of site-specific functionalization [12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27], allowing the generation of different metalinduced DNA nanoarchitectures. Several promising applications have already been established in this (a)

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