Metal-mediated base pairs represent a powerful tool for the site-specific functionlization of nucleic acids with metal ions. The development of applications of the metal-modified nucleic acids will depend on the availability of structural information on these double helices. We present here the NMR solution structure of a self-complementary DNA oligonucleotide with three consecutive imidazole nucleotides in its centre. In the absence of transition-metal ions, a hairpin structure is adopted with the artifical nucleotides forming the loop. In the presence of Ag(I) ions, a duplex comprising three imidazoleAg+-imidazole base pairs is formed. Direct proof for the formation of metal-mediated base pairs was obtained from (1) AbstractMetal-mediated base pairs represent a powerful tool for the site-specific functionalization of nucleic acids with metal ions. The development of applications of the metal-modified nucleic acids will depend on the availability of structural information on these double helices. We present here the NMR solution structure of a self-complementary DNA oligonucleotide with three consecutive imidazole nucleotides in its centre: In the absence of transition metal ions, a hairpin structure is adopted with the artificial nucleotides forming the loop. In the presence of silver(I) ions, a duplex comprising three imidazole-Ag + -imidazole base pairs is formed.Direct proof for the formation of metal-mediated base pairs was obtained from 1 J( 15 N, 107/109 Ag) couplings upon incorporation of 15 N-labelled imidazole. The duplex adopts a B-type conformation with only minor deviations in the region of the artificial base pairs. This structure represents the first example of a metal-modified nucleic acid with a continuous stretch of metal-mediated base pairs.3 Nucleic acids such as DNA are becoming increasingly popular as versatile building blocks in nanobiotechnology as a result of their superb, predictable self-assembling properties and the high rigidity of their double helices on the nanoscale. 1 Their applicability can be extended even further by the introduction of functional groups such as metal ions. One recently established method for the site-specific functionalization of nucleic acids with metal ions is based on the use of metal-mediated base pairs. 2-5 Such base pairs comprise natural or artificial nucleobases and rely on coordinative bonds to a central metal ion instead of (or in addition to) hydrogen bonds. Depending on the choice of nucleosides, metal ions, and oligonucleotide sequence, a plethora of metal-modified double helices can be generated. Even if focussing only on the use of artificial nucleosides, examples exist for DNA duplexes containing one or two metal-mediated base pairs interspersed between natural ones, 6-8 DNA double helices with continuous stretches of metalated base pairs, 9-11 and DNA duplexes with different metalmediated base pairs at pre-defined positions. 12 When including also metal-mediated base pairs from natural nucleosides, 13-15 even more combinations can ...

Excess electron transfer through one set of DNA duplexes comprising either one or two metal-mediated thymine-Hg -thymine base pairs was studied. Towards this end, the metal-mediated base pair(s) were introduced between an artificial nucleoside bearing a N,N,N',N'-tetramethyl-1,5-diaminonaphthalene derivative (dN, acting as a photoinducible electron donor) and 5-bromo-2'-deoxyuridine (dB, acting as an electron acceptor). Upon one-electron reduction, dB loses a bromide ion. The amount of unreacted dB remaining after irradiation-determined by LC/ICP-MS-was used to evaluate the charge-transfer efficiency across the metal-mediated base pair(s). Reference measurements with canonical adenine:thymine base pairs prove the applicability of this approach for the detection of charge transfer in DNA. The data indicate that, for the set of DNA duplexes under investigation, excess electron transfer across a thymine-Hg -thymine base pair proceeds with low efficiency, comparable to the transfer across a thymine:thymine mispair. Two contiguous thymine-Hg -thymine base pairs effectively shut down excess electron transfer.

SummaryThe imidazole–Ag(I)–imidazole base pair is one of the best-investigated artificial metal-mediated base pairs. We show here that its stability can be further improved by formally replacing the imidazole moiety by a 2-methylimidazole or 4-methylimidazole moiety. A comparison of the thermal stability of several double helices shows that the addition of one equivalent of Ag(I) leads to a 50% larger increase in the melting temperature when a DNA duplex with methylated imidazole nucleosides is applied. This significant effect can likely be attributed to a better steric shielding of the metal ion within the metal-mediated base pair.

Metal-mediated base pairs are transition metal complexes formed from complementary nucleosides within nucleic acid double helices. Instead of relying on hydrogen bonds, they are stabilized by coordinative bonds. The nucleosides acting as ligands do not necessarily have to be artificial. In fact, several examples are known of naturally occurring nucleobases (e.g., thymine, cytosine) capable of forming stable metal-mediated base pairs that are highly selective towards certain metal ions. This chapter provides a comprehensive overview of metal-mediated base pairs formed from natural nucleosides or from closely related artificial nucleosides that are pyrimidine or purine derivatives. It addresses the different strategies that lead to the development of these base pairs. The article focuses on structural models for metal-mediated base pairs, their experimental characterization within a nucleic acid, and on their possible applications.

The incorporation of an artificial 5-methyl-2,2'-bipyridine nucleoside at the 5' terminus of an otherwise self-complementary oligonucleotide sequence opens up the opportunity of metal-mediated aggregation of DNA double helices triggered by the addition of the respective metal ions. Interestingly, two-dimensional aggregates (DNA monolayers) are formed in the presence of nickel(ii), whereas copper(ii) leads to the formation of three-dimensional disc-shaped structures. With iron(ii), a coexistence of both types of aggregates had been observed previously. Models are proposed in which these observations are explained based on geometrical considerations. The artificial nucleoside itself represents a rare example for a C(1)-symmetric chiral derivative of 2,2'-bipyridine, enabling the formation of four isomeric octahedral complexes.