Hans-Christian Kliem

Synthesis of new boron-rich building blocks for boron neutron capture therapy or energy-filtering transmission electron microscopy.

The synthesis of a new ortho‐carborane derivative, tetracarboranylketone 4, is reported here. Ketone 4 was prepared from a tetraalkynylated ketone by the addition of decaborane. The keto group was then easily modified to yield the glycosides 17α and 18β, which contain glucose or galactose, respectively, and the nucleotide 13 b. In addition to ketone 4, which is acyclic, cyclic ketone 8 was also synthesised. X‐ray diffraction analysis of compound 4 indicated the presence of two toluene guest molecules per molecule of the host compound. Furthermore, compound 4 displays a rather low cytotoxicity. These novel products can be used as building blocks to create a new class of biomolecules containing high‐density carborane clusters. Such molecules may constitute powerful tools for applications like Boron Neutron Capture Therapy or Energy‐Filtering Transmission Electron Microscopy.

Synthesis of fluorescently labeled alkylated DNA adduct standards and separation by capillary electrophoresis

DNA adducts are regarded as individual internal dosimeters for the exposure to chemical carcinogens. To date, the most sensitive method for DNA adduct analysis is the radioactive 32P‐postlabeling method, which allows the detection of one adduct in 1010 unmodified nucleotides in μg amounts of DNA. However, this technique suffers from disadvantages such as working with radioactive phosphorus and time‐consuming chromatographic separation procedures. In addition, the simultaneous detection of adducts from different classes of carcinogens in a DNA sample is difficult. In order to overcome these drawbacks, we are developing a new detection method, comprising fluorescence labeling of DNA adducts, capillary electrophoretic (CE) separation, and on‐line detection by monitoring laser‐induced fluorescence (LIF). So far, we have evaluated the separation power and the detection limit of CE with fluorescently labeled standard compounds such as unmodified nucleotides or alkylated thymidines. For this purpose, we developed a universal method for labeling 5′‐OH‐mononucleosid‐3′‐dicyanoethyl‐phosphates with fluorescent dyes based on the phosphoramidite technology for DNA synthesis. The separation of N3‐methylated, N3‐, O2‐ and O4‐butylated thymidines from the unmodified nucleotide within a few minutes recommends CE‐LIF as a powerful method for DNA adduct analysis.