Synthesis and properties of a Cu(ii) complexing pyrazole ligandoside in DNA

Abstract

The development of metal base pairs is of immense importance for the construction of DNA nanostructures. Here we report the synthesis of a biaryl pyrazole-phenol nucleoside that forms in DNA a stable self-pair upon complexation of a Cu(II) ion. A sequence with five consecutive pyrazole nucleotides allows the complexation of five Cu(II) ions in a row.We are currently experiencing the increased use of DNA strands for the defined construction of two and three dimensional nanoobjects. 1-3 Nowadays DNA nanoconstructions allow not only the assembly of nanoobjects with complex shapes, but also of nanosystems that feature new unusual functions. [4][5][6] Examples include the decoration of DNA structures with catalytically competent or sensoring proteins, 7-9 and the construction of cage-like DNA nanoobjects for the encapsulation of cargo that is released by a defined outside stimulus. 10 Currently it is of interest to create DNA nanostructures that exhibit novel electronic and magnetic properties. This would allow the controlled assembly of nanomagnets or electronically switchable devices. Taking advantage of the interesting electronic and magnetic properties of the metal ions with unpaired electrons, research has focused on the design of metal complexing ligandosides capable of complexing such metal ions in the DNA duplex. 11 Alternatively, the incorporation of metal ions into DNA might allow the design of new catalytically competent nanosystems at the boundary between homogenous and heterogenous catalysis. 12 Fig. 1 shows the ligandosides 1-3, which were so far designed for the stable incorporation of Cu(II) ions into the duplex. [13][14][15] Here we report the preparation of a new Cu(II) complexing ligandoside 4, and its easy incorporation into the DNA duplex by using standard phosphoramidite chemistry. With this new biaryl-type ligandoside the system is able to accomodate five Cu(II) ions on top of each other within the duplex.The straightforward synthesis is depicted in Scheme 1A. The starting point is 2-amino-5-bromo-anisole (5) which was, after nitrosation, converted to the pyrazole 6 by generation of the diazonium salt. Deprotection of the methoxy group to the phenol derivative 7 followed by silyl protection provided the key intermediate 8 in 58% overall yield. Cuprate based coupling of 8 with the toluoylprotected a-2 0 -deoxyribosylchloride 9 16 led to the b-configured nucleoside 10 in 53% yield. 17 Saponification of the sugar ester groups in methanol to give 11 was followed by 5 0 -DMT protection (compound 12) and generation of the desired phosphoramidite 13 using standard procedures. To unambiguously determine the geometry of the ligandoside, compound 11 was deprotected, crystallized and the crystal structure of the resulting compound 14 was solved.In order to learn more about the complexing behaviour we next synthesized the ligandoside 17 in which the phenolic hydroxyl group is permanently blocked (Scheme 1B). To this end the TIPS and toluoyl-protected intermediate 10 was selectively TIPS-deprotected (compou...

DNA based multi-copper ions assembly using combined pyrazole and salen ligandosides

“…We synthesized the pyrazole ligandosides Pz and Pm according to our published procedure. 46 Table 1 summarizes the modified DNA single strands prepared for this work.…”

“…1b . 46 This ligandoside construction lacks the bridge but still retains the same metal coordination geometry.…”

“…1b. 46 This ligandoside construction lacks the bridge but still retains the same metal coordination geometry. Here we present stability and selectivity studies with the Pz ligandoside.…”

Palladium-Catalyzed Chelation-Assisted Regioselective Oxidative Dehydrogenative Homocoupling/Ortho-Hydroxylation in N-Phenylpyrazoles

“…We have an ongoing program for formulating general routes to pyrazole derivatives of biological significance . During the course of this work, we noticed that recently several compounds bearing a 1-(2-hydroxyphenyl)­pyrazole subunit were reported to be useful as antifungal agents I , as antitrichophytic adhesive patch, in the treatment of dermatophytosis and N-type Ca-channel blockers II , as β-secretase inhibitors III , and as Cu­(II)-complexing ligandoside in DNA IV (Figure ). Established routes to their synthesis required starting reactants bearing the hydroxyl group which were either used directly or in the protected form.…”

Artificial DNA Base Pairing Mediated by Diverse Metal Ions

“…Other [N,O]-type artificial nucleosides include a pyrazolylphenol-bearing one (Pz), which has a pyrazole and a phenol as metal coordination sites (Figure 7e). 63,78 A Cu(II)-mediated base pair, PzCu II Pz, was formed under basic conditions because the metal complexation of the Pz ligand requires the deprotonation of the phenolic groups. Incorporation of consecutive PzCu II Pz base pairs allowed discrete assembly of up to ten Cu 2+ ions inside the DNA duplexes.…”