Octanol-water partition coefficients of highly hydrophobic photodynamic therapy drugs: A computational study

Photodynamic therapy is a novel treatment for solid tumors based on the selective induction of cell death by the generation of cytotoxic reactive oxygen species within neoplastic tissues. Oxygen photosensitization is promoted as a consequence of the activation (using light) of a photosensitizer, which must reach the desired tissue by cellular transport. Hydrophobicity (expressed as the logarithm of octanol/water partition coefficient, logP), becomes a key factor in these processes. Unfortunately, there is no computational method to unambiguously predict the logP value for high hydrophobic photosensitizers. In this study, a total of 12 computational methods have been tested for predicting the logP value of tetrapyrrolic derivatives. Furthermore, in the attempt to correlate logP with experimental HPLC measurements (log(k')), validation of the results leads to the proposal of a sigmoidal regression for the two parameters (log(k') and logP).