Nucleic acid chemistry: New building blocks and postsynthetic methodologies

With respect to various biological and non-biological applications of DNA and RNA, the synthesis of new nucleic acid building blocks is an ongoing endeavour. In our group, we synthetically introduce new functionalities by two different alternatives: (i) DNA base modifications and (ii) artificial DNA base substitutes. Postsynthetic modification of nucleic acids is a well-established methodology and mainly performed by copper-catalyzed cycloadditions between acetylenes and azides. The reliance on copper catalysis is problematic since even traces of copper ion impurities from the postsynthetic or in-vivo modification represent a major drawback due to cytotoxicity. Hence, our current research in nucleic acid chemistry focuses on the development of bioorthogonal and copper-free click-type alternatives for nucleic acid modification. This includes strain-promoted and other 1,3-dipolar cycloadditions,  Diels-Alder reactions with inverse electron demand, and the light-induced cycloaddition between tetrazoles and activated alkenes.


Chemical photocatalysis: Sustainability by light and organic dyes

Photocatalysts are compounds that couple the physical process of light absorption with a chemical reaction by means of time, space and energetics, in order to catalyse it. With respect to the “green” character of sunlight as sustainable while unlimited natural light source and the availability of LEDs as energy-saving, cheap and reliable artificial light sources, the research field of photoredox catalysis has tremendously grown over the past decade. Transition metal complexes, mainly [Ru(bpy)3]2+, were most often used as photocatalysts, whereas the potential of organic compounds and dyes has not yet been fully exploited. The way towards more sustainability meaning a really complete organo-type photoredox catalysis has mainly been established for eosin Y as an important alternative for [Ru(bpy)3]2+. We focus our research on the use of substituted pyrenes, substituted perylene bisimides and naphthalene diimides as organic catalysts for a variety of reactions.

Fluorescent DNA and RNA: Photostability and cellular imaging of nucleic acids

Molecular imaging represents the most powerful technique to visualize not only subcellular structures but to follow the action of nucleic acids inside cells in real time. A great variety of fluorescent probes and nanoparticles is available for biological imaging, especially for fluorescent tagging of proteins. In contrast, tailor-made fluorescent labeling of nucleic acids for molecular imaging has remained challenging. This stands in contrast to the central importance of DNA and RNA in cellular functions. Hence, visualizing of nucleic acids represents an important goal for chemical biology. Fluorescent probes can be introduced synthetically by providing the corresponding DNA building blocks. If such building blocks were synthetically not obtainable or fluorescent probes are not compatible with the broadly applied phosphoramidite chemistry, postsynthetic methodologies allowed the modification of oligonucleotides. Moreover, polymerase-assisted biochemical syntheses of labeled oligonucleotides were achieved, first tested in primer extension experiments (PEX) and subsequently applied for amplification of DNA by PCR. This allowed us developing wavelength-shifting fluorescent probes (“DNA/RNA Traffic Lights”) as a powerful tool for molecular imaging. Moreover, the styryl dyes of the cyanine indole quinoline type and corresponding derivatives represents an important photostable alternatives.



DNA architectonics: Biomolecular architectures with optical and electronic functionalities

Nucleic acids have been emerging as a supramolecular structural scaffold for the helical organization of chromophores in the creation of functional nanomaterials mainly because of the its unique structural features and the synthetic accessibility. A large number of chromophores have been successfully incorporated into DNA as C-nucleosides, as base surrogates or as modified sugars using the solid phase phosphoramidite chemistry. Moreover, multiple incorporations yield the helical organization of the chromophores inside or outside the DNA double helix depending upon the conjugation of the chromophores. Significant photophysical interactions are observed in the chromophore stacks resulting in unique optical properties that are significantly different from the monomer properties. DNA serves also as a template for the supramolecular organization of organic chromophores in a non-covalent fashion. Moreover, one-dimensional electron transfer along DNA double strands is a promising feature for molecular electronics, which has attracted considerable interest not only in our group. For instance, carefully designed hydroxyquinoline base pairs promote photoinduced electron transfer and allows to construct a DNA-based system that allows to support long-range electron hopping by providing synthetic stepping stones for the electron. These results supports the potential of DNA-based architectures for applications in material chemistry, light harvesting systems and nanoelectronics.