Unsymmetrically Substituted Benzonaphthoporphyrazines: A New Class of Cationic Photosensitizers for the Photodynamic Therapy of Cancer*

Unsymmetrical zinc(II) complexes of benzonaphthoporphyrazines 5a-12a bearing between one and eight pyridyloxy substituents are synthesized by statistical tetramerization of 6-(1,1-dimethylethyl)-2,3-naphthalenedicarbonitrile (1) with 4-(3-pyridyloxy)- or 4,5-bis-(3-pyridyloxy)-1,2-benzenedicarbonitrile (2, 3). Methylation of 5a-12a leads to the catianic pyridyloxybenzonaphthoporphyrazines 5b-12b having between one to eight positive charges. The Q-band transition in the visible spectra exhibits a bathochromic shift from 680 to 760 nm dependent upon the number of annelated naphthalene rings. The singlet oxygen quantum yields of the benzonaphthoporphyrazines determined by the dye-sensitized photooxidation of 1,3-diphenylisobenzofurane is surprisingly high (in the range of zinc phthalocyanine). The photooxidative stabilities of the photosensitizers described quantitatively by first-order kinetics decrease with the number of annelated naphtho groups. A linear correlation between the logarithm of the decomposition rate constant and the position of the highest occupied molecular orbital (HOMO)-level of the photosensitizers is found. Destabilization of the HOMO leads to a decrease of the photostability. Due to their adjustable long wavelength absorption, their intramolecular polarity axis and their different hydrophilic/hydrophobic character, these novel compounds may be suitable photosensitizers for the photodynamic therapy of cancer.