Research topic of Till Kuehn:
An ab initio Approach regarding an Explanation of the Exceptional Status of the 2,3,7,8-Positions in Dibenzodioxins
In cooperation with Dr. Roland Weber.
During the hydroxylation of aromatic systems by P450 oxygen has to be transferred from the enzyme towards the aromatic system (via epoxidation). In principle, an electrophilic aromatic substitution is held responsible for this step. Consequently, a high electron density in the aromatic system should facilitate this reaction. This is demonstrated by the fact that the metabolization rate is (on the average) decreased by an increase in the fluorination degree. This also could be used to explain why the less polar TCDD (2,3,7,8; 1,4,6,9; 1,3,6,8; 1,2,6,7) show a slower degradation than the more polar congeners (1,2,8,9; 1,3,7,9; 1,2,6,9) because their electron density is distributed more homogeneously over the whole molecular framework. Thus, they are less prone to a localized electrophilic attack. But a successful explanation for the exceptional position of the 2,3,7,8-substituted congeners is still missing. The reason for the specific hydroxylation of the unsubstituted dibenzodioxin in the lateral position also has to be found. It was concluded that by looking at the electron densities of the aromatic systems of interest one should get reasonable insight into this aspect. Thus, the aromatic systems were investigated by means of quantum mechanical ab initio calculations to give a first estimate of the electron density distributions as well as orbital effects in these systems.