On the Usefulness of Graph-theoretic Descriptors in Predicting Theoretical Parameters. Phototoxicity of Polycyclic Aromatic Hydrocarbons (PAHs)

摘要

Two main aspects on the use of theoretical approaches in predicting biological endpoints are addressed. The first concerns the appropriateness of theoretical methods and the misbelief that more sophisticated approaches produce better results. We demonstrate that the simple graph theoretic HMO approach produces results as good as »high level« ab initlo calculations using only 10~(-4) to 10~(-4) of the time. Secondly, we investigate the feasibility of using a priori »mecha-nistic insights« in order to select the variables to be included in a QSAR model. As the majority of biological response measures are not specific for one particular mechanism, the use of this approach may well produce unrealistic results. The black box approach with its many descriptors and a posteriori interpretation of the results is much more appropriate in such cases where the biological response is the result of several mechanisms involving distribution and metabolism. All these aspects are analysed on the basis of the toxicity of PAHs after photo-activation by UV radiation.