Project

nucleic acids; fluorescence; aromatic stacking; self-organization; aromatic hydrocarbons; molecular beacon; supramolecular chemistry; charge transfer

Lead
Lay summary
Lead:DNA serves as a framework for the construction of well-defined structures on the nanometer scale. The formation and the properties of ordered aggregates of aromatic chromophores in a DNA duplex are investigated.Background:Arrays of various types of aromatic compounds can be generated by inserting segments of suitable derivatives into a DNA framework or by using the double helix as a scaffold for placement of appended chromophores. In addition to opening the way to novel types of materials with potentially useful spectroscopic, electronic or physical properties, oligonucleotide-chromophore conjugates may also lead to improved types of diagnostic tools. The rational formation of aromatic chromophore arrays is an intriguing challenge since ordered collectives of chromophores possess largely different properties than the individual molecules. Due to its repetitive and well-defined structural features DNA is a practical tool for the generation of nanometer-sized structures. Thus, the approach of using nucleic acids as a guiding frame for the formation of highly ordered chromophore assemblies has emerged over the past few years as a new research direction.Goals:Building upon the results obtained in the past with pyrene and related polyaromatic compounds, we are using DNA-chromophore conjugates for the assembly of multi-stranded architectures. The synthesis and evaluation of novel types of non-nucleosidic chromophores will be pursued. While we continue the investigation of additional types of pyrene derivatives we will extend our efforts to the synthesis of quinoxaline and porphyrin derivatives. The newly synthesized compounds will be evaluated for their stacking behaviour as well as their spectroscopic properties. Crucial aspects are the ability to assist hybrid formation, the fluorescence properties, and the compatibility with oligonucleotide synthesis. Additionally, we will extend our investigations of artificial helical systems formed by oligomers of pyrene and other building blocks. The amplification of chirality observed in a system composed of chiral and achiral oligopyrenes suggests that the oligomers undergo supramolecular polymerization. A further goal is the investigation of electron transfer through non-nucleosidic, aromatic building blocks.Significance:The use of DNA as an intelligent scaffold that allows the precise placement of functional molecules may open a way to novel types of materials with potentially useful spectroscopic, electronic or physical properties. In addition, oligonucleotide-chromophore conjugates may lead to improved types of diagnostic tools for the early detection of infective or genetic diseases.

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Last update: 21.02.2013

Active participation

Self-organised

Communication	Title	Media	Place	Year

Number	Title	Start	Funding scheme

The construction and investigation of nucleic acid-guided, supramolecular structures is proposed. Building upon the results obtained in the past with pyrene and related polyaromatic compounds, we will use DNA-chromophore conjugates for the assembly of multi-stranded architectures. The synthesis and evaluation of novel types of non-nucleosidic chromophores will be pursued. At the same time, the spectroscopic and structural characterization of extended chromophore arrays is becoming a major aspect of our reserach.In a first part, we will explore new classes of aromatic building blocks. While we continue the investigation of additional types of pyrene derivatives we will extend our efforts to the synthesis of quinoxaline and porphyrin derivatives. The newly synthesized compounds will be evaluated for their stacking behaviour1,2 as well as their spectroscopic properties. Crucial aspects are the ability to assist hybrid formation, the fluorescence properties, and the compatibility with oligonucleotide synthesis. The proposed quinoxaline derivatives will provide an easy access to an extended library of compounds. Preliminary analysis of the spectroscopic properties of a first member of the series showed promising properties (high extinction coefficient and good quantum yield). The synthesis of the porphyrin derivatives as well as their incorporation into oligonucleotides is considerably more challenging. Considering the unique electronic properties of the porphyrins, the preparation of covalently linked stacks of defined length and composition is a worthy endeavour, however.3,4Secondly, we will extend our investigations of artificial helical systems formed by oligomers of pyrene and other building blocks. The amplification of chirality observed in a system composed of an achiral oligopyrene and traces of a (chiral) pyrene oligomer containing a single deoxynucleotide suggests that, under certain conditions, the oligomers form supramolecular polymers. The properties of these macromolecular assemblies will be further investigated with the different spectroscopic methods available. Along the same lines, we will explore the rational formation of molecular nanowires with bi-segmental oligomers composed of DNA and artificial building blocks (pyrene or PDI). Potential insight into the nature of these polymeric structures may be obtained through a collaborative effort with the group of T. Wandlowski of our department.Thirdly, the possibility of chemical ligation and template-assisted chain elongation of oligopyrenotides will be investigated. The formation of multi-stranded hybrids by oligopyrene strands via interstrand stacking interactions opens the opportunity of testing the formation of phosphodiester bonds from activated phosphate esters on (oligopyrene) template strands. Although not as efficient as enzymatic phosphodiester bond formation by enzymatic means and with natural substrates, such type of a templated oligomerization might provide a way to primitive, self-reproducing systems, especially if more than one type of building block were used.In a further part we will prepare modified hybrids that will allow the investigation of the efficiency of electron transfer through pi-stacks of non-nucleosidic, aromatic building blocks. For this purpose, oligomers containing pyrene (electron acceptor) and a quencher (electron donor) which are separated by a polyaromatic building block (e.g. phenanthrene) will be prepared. The determination of the relative fluorescence quantum yields will give information on the photo-induced electron transfer process.In addition to the above mentioned activities we will continue our efforts with the development of excimer based molecular beacons. In collaboration with the Department of Clinical Research (Prof. R. Jaggi), we will test differently designed beacon stems for their suitability for PCR and other applications.