N,N,O and N,O,N Meridional cis Coordination of Two Guanines to Copper(II) by d(CGCGCG)2.

Many research groups study the generation of supramolecular n-dimensional arrays by combining metals with DNA building blocks. Most of the time, the natural nucleobases are modified to obtain higher-affinity metal binding sites. Using unmodified nucleobases avoids a potentially difficult synthesis; however, they have the possible disadvantage of a less defined and/or weaker coordination mode of the metal. Structural studies on the behavior of copper(II) as a linking metal and guanine as the natural ligand for metals in unmodified DNA are reported. Previously, the ability of mono- and dinuclear metal complexes to induce Z-DNA has been explored [Medina-Molner, A.; Spingler, B. Chem. Commun. 2012, 48, 1961; Medina-Molner, A.; Rohner, M.; Pandiarajan, D.; Spingler, B. Dalton Trans. 2015, 44, 3664]. Herein, X-ray crystallographic studies of the structures resulting from the combination of copper(II) ions with DNA hexamers of the general sequence d(CG)3 are presented. Three different packing motifs were observed in three crystal structures with resolutions ranging from 2.15 to 1.45 Å. The motifs are dependent upon other cations being present and/or the crystallization conditions. The first examples of intramolecular O6,N7-chelates of a neutral purine nucleobase to copper(II) were obtained as well as the first meridional N,N,O and N,O,N coordination modes of two guanines to copper(II). The fascinating coordination chemistry of copper(II) complexes generated by the Z-DNA oligonucleotides and the differences to simple nucleobases complexes with copper(II) are discussed in detail.

Mono- and dinuclear metal complexes containing the 1,5,9-triazacyclododecane ([12]aneN3) unit and their interaction with DNA.

The ability of mononucleating and dinucleating macrocylic polyamines and their novel nickel, copper and zinc complexes to induce the left-handed form of poly d(GC) was evaluated. The influence of the nuclearity, the presence or absence of metals ions, the linker length in the case of dinucleating ligands and the metal ion was determined. Almost all dinuclear metal complexes efficiently induced Z-DNA, the zinc ones being the least and the copper ones the most efficient ones. Additionally, the X-ray structures of three dinuclear metal complexes and one partially protonated ligand could be determined.

When two metal centres are needed instead of one: exclusive induction of Z-DNA by dinuclear metal complexes.

The B- to Z-DNA transition was very efficiently induced by dinuclear nickel and copper complexes based on the 1,3-bis(1,5,9-triazacyclododecyl) propane ligand but not by the corresponding mononuclear complexes. This dramatically different behaviour is explained by the formation of a macrochelate of the dinuclear complexes to the DNA.

The synthesis of 1,2-bis(1,5,9-triazacyclododecyl)ethane: a showcase for the importance of the linker length within bis(alkylating) reagents.

The synthesis of 1,2-bis(1,5,9-triazacyclododecyl)ethane (1) showcases how different bis(alkylating) reagents change the reaction from an intra- to an intermolecular pathway. The isolation of the intermediate hexahydro-3a,6a-ethano-1H,4H,7H,9bH-9a-aza-3a,6a-diazoniaphenalene-3a,6a-diium (2) explained why initially the synthesis of 1 was not possible. Both isomers of 2 were found in solution. DFT calculations revealed that isomer 2a is 4.6 kcal/mol lower in energy than 2b. Synthesis of 1 was finally achieved by using oxalyl chloride.

Structural analysis of Cu(II) ligation to the 5'-GMP nucleotide by pulse EPR spectroscopy.

Simple copper salts are known to denature poly d(GC). On the other hand, copper complexes of substituted 1,4,7,10,13-pentaazacyclohexadecane-14,16-dione are able to convert the right-handed B form of the same DNA sequence to the corresponding left-handed Z form. A research program was started in order to understand why Cu(II) as an aquated ion melts DNA and induces the conformational change to Z-DNA in the form of an azamacrocyclic complex. In this paper, we present a continuous wave and pulse electron paramagnetic resonance study of the mononucleotide model system Cu(II)-guanosine 5'-monophosphate . Pulse EPR methods like electron-nuclear double resonance and hyperfine sublevel correlation spectroscopy provide unique information about the electronic and geometric structure of this model system through an elaborate mapping of the hyperfine and nuclear quadrupole interactions between the unpaired electron of the Cu(II) ion and the magnetic nuclei of the nucleotide ligand. It was found that the Cu(II) ion is directly bound to N7 of guanosine 5'-monophosphate and indirectly bound via a water of hydration to a phosphate group. This set of experiments opens the way to more detailed structural characterization of specifically bound metal ions in a variety of nucleic acids of biological interest, in particular to understand the role of the metal-(poly)nucleotide interaction.