Investigation By NMR Spectroscopy of the Structural Characteristics of Modified Oligo-Nucleotides with Pendant Porphyrins

Abstract

Exerting control over the position and distance of the porphyrins along a specifically designed oligonucleotidic scaffold was our main goal over the past years. Indeed, in naturally occurring light-harvesting complexes, biopolymer scaffolds hold pigments at intermolecular distances that optimize photon capture, electronic coupling, and energy transfer. We thus focused on the synthesis of four uridine-porphyrin conjugates (a monomer, dimer, tetramer and octamer) dedicated to adopt a pre-organized conformation with face-to-face porphyrins, and capable to self-organize in a stable sandwich type complexe with bidentate base such as DABCO. Using a similar strategy as the one used in antisense research, an artificial nucleotidic backbone was built from modified deoxy-uridine units linked with a more rigid linker than the phosphodiester moieties found in natural oligonucleotides. Antisense research uses modified oligonucleotides, less flexible than natural strands, to pre-organize the system toward the obtaining of stable double helices between synthesized and natural oligonucleotides. A modified oligonucleotidic backbone was here used to target a parallel conformation of the porphyrins appended to each deoxy-uridine moiety. To provide a rigid environment for the porphyrins, the uridine units were coupled in 3’-5’ stepwise fashion using ether-ester type of spacer of suitable length, and porphyrins were anchored to the uridine by means of robust carbon-carbon bonds. To investigate the conformation of our four uridine-porphyrin conjugates, they were subjected to a comprehensive conformational analysis by using NMR spectroscopy. The collected NOE NMR data highlighted characteristic and strong interactions indicating that the glycosidic angle between the ribose and uracil base is anti. In order to further invastigate the conformation of this family of molecules, NMR experiments were carried out at variable temperature. At low temperature, the signals of the porphyrinic protons decoalesce showing two sets of b-pyrrolic protons. Similar observations are made for the signals corresponding to the sugar moieties and especially the H1’ protons, indicating molecular motions within our porphyrin-uridin arrays. These results testify in favor of the existence of a dynamic process between C3’-endo and C2’-endo conformations. We thus document the fact that the choice of rigid spacers is not the only way to pre-organize bis-porphyrins, and that some well-chosen nucleosidic linkers offer an interesting option for the synthesis of such devices. Furthermore, the chirality and enantio-purity of the nucleosidic linkers paves the way toward the selective complexation of enantio-pure bidentate guests and the resolution of racemates. Acknowledgements This work was supported by the CNRS and the French Ministry of Research.