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 ...

To evaluate the possibility of introducing azole nucleosides as building blocks for metal-mediated base pairs in artificial oligonucleotides, imidazole nucleoside, 1,2,4-triazole nucleoside and tetrazole nucleoside have been synthesized and characterized. The X-ray crystal structures of p-toluoyl-protected 1,2,4-triazole and tetrazole nucleosides are reported. Contrary to the situation primarily found for deoxyribonucleosides, the sugar moieties adopt C3'-endo conformations. The acidity of the beta nucleosides increases with increasing number of nitrogen ring atoms, giving pKa values of 6.01 +/- 0.05, 1.32+/-0.05 and <-3, respectively. This decrease in basicity results in a decreasing ability to form 2:1 complexes with linearly coordinating metal ions such as Ag+ and Hg2+. In all cases, the Ag+ complexes are of higher stability than the corresponding Hg2+ complexes. Whereas imidazole nucleoside forms highly stable 2:1 complexes with both metal ions (estimated log beta2 values of >10), only Ag+ is able to reach this coordination pattern in the case of triazole nucleoside (log beta2 = 4.3 +/- 0.1). Tetrazole nucleoside does not form 2:1 complexes at all under the experimental conditions used. These data suggest that imidazole nucleoside, and to a lesser extent 1,2,4-triazole nucleoside, are likely candidates for successful incorporation as ligands in oligonucleotides based on metal-mediated base pairs. DFT calculations further corroborate this idea, providing model complexes for such base pairs with glycosidic bond distances (10.8-11.0 Angstroms) resembling those in idealized B-DNA (10.85 Angstroms).

A conformational switch can be induced upon the addition of transition-metal ions to oligonucleotides that contain a row of successive artificial nucleobases flanked by complementary sequences of natural nucleobases, provided that the artificial bases cannot undergo self-pairing via hydrogen bonding but only via the formation of metal-ion-mediated base pairs. Such oligonucleotides adopt a hairpin structure in the absence of transition-metal ions, yet they show a preference for the formation of a regular double helix if the appropriate metal ions are present. We report here our experimental data on the structure of the oligonucleotide d(A7X3T7) (A=adenine, T=thymine, X=1,2,4-triazole) in the absence and presence of silver(I). This study comprising temperature-dependent UV spectroscopy, CD spectroscopy, MALDI-TOF measurements, fluorescence spectroscopy, and dynamic light scattering opens up a new approach to the generation of a large variety of metal-ion sensors with the possibility of fine-tuning their sensing capabilities, depending on the artificial nucleoside that is used.

Metal-mediated base pairs can be used to insert metal ions into nucleic acids at precisely defined positions. As structural data on the resulting metal-modified DNA are scarce, appropriate model complexes need to be synthesized and structurally characterized. Accordingly, the molecular structures of nine transition metal complexes of N-methyl-2,2'-dipicolylamine (dipic) are reported. In combination with an azole-containing artificial nucleoside, this tridentate ligand had recently been used to generate metal-mediated base pairs (Chem. Commun. 2011, 47, 11041-11043). The Pd II and Pt II complexes reported

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