Phenothiazine photosensitizers: part 2. 3,7-Bis(arylamino)phenothiazines

The synthesis and characterisation of a series of phenothiazines for possible use in photochemotherapy is reported. Oxidative amination of 10H-phenothiazine using anilines and iodine in tetrahydrofuran led to a series of 3,7-bis(arylamino)phenothiazin5-ium salts. 4-Substituted primary anilines gave rise to a secondary amino functionality at positions 3- and 7- of the phenothiazine chromophores. The relative ease of deprotonation of these compounds to the corresponding quinoneimines correlated well with the electronic properties of the 4-substituent in the original aniline. In vitro singlet oxygen yields for these derivatives were much lower than for the standard photosensitizer, methylene blue. The use of N-methylaniline did not lead to increased photosensitizing efficacy. However, the phenothiazines resulting from the use of benzylamines in place of anilines were more akin to new methylene blue N. All of the derivatives exhibited much greater lipophilicities than methylene blue.