Synthesis and characterization of a metal-salen base pair for the assembly of programmed metal arrays inside the DNA double helix

Base pairing in natural oligonucleotides relies on hydrogen bonding
and pi-stacking. Applying coordinative interactions between
ligand-like nucleobases and metal cations is a new way of
assembling artificial oligonucleotide duplexes. The incorporation
of numerous metal-base pairs into oligonucleotides may lead to
interesting compounds for nano-technological applications. In this
thesis, the synthesis of the salen-metal base pair is described,
which comprises preparation of a suitable protected salicylic
aldehyde precursor and an organo-cuprate mediated C-glycosidation
as the key step. An x-ray structure of the monomeric copper-salen
base pair shows a very good geometrical match with natural
Watson-Crick base pairs. Up to 10 consecutive salicylic
aldehyde-nucleobases could be incorporated into DNA
oligonucleotides by means of phosphoramidite chemistry. The
synthesized double strands with one ligand show typical B-DNA
CD-spectra and distinct melting characteristics. Addition of excess
ethylenediamine and 1 eq of Mn2+ or Cu2+ increase the melting temp.
by 28 °C and 42 °C, respectively. The complexation of these and
other metals was examined by UV-, CD- and EPR-spectroscopy and high
res. ESI mass spectrometry. It was possible to stack 10 manganese
atoms inside the double helix and to prepare sequence specifically
arrays of up to 5 copper ions plus 5 mercury ions inside one
duplex.