Synthesis, dark toxicity and induction of in vitro DNA photodamage by a tetra(4-nido-carboranylphenyl)porphyrin.

The total synthesis of tetra(4-carboranylphenyl)porphyrins 4 and 6 and their zinc(II) complexes 5 and 7 are described. These compounds were characterized by analytical and spectroscopic methods and, in the case of 5, by X-ray crystallography. The water-soluble nido-carboranylporphyrins 6 and 7 were found to have low dark toxicity towards V79 hamster lung fibroblast cells, using a clonogenic assay (50% colony survival, CS(50)>300 microM). Upon light activation nido-carboranylporphyrin 6 effectively induced DNA damage in vitro. Two different methods were used to assess the extent of DNA damage: the super-coiled to nicked DNA and the alkaline Comet assay using human leukemia K562 cells. Significant PDT-induced DNA damage was observed for porphyrin 6 using both assays, compared to light-only and porphyrin-only experiments. It is concluded that this type of nido-carboranylporphyrin is a promising sensitizer for both the boron neutron capture therapy and the photodynamic therapy of tumors.

Preparation, characterization, and luminescence properties of gallium-metal face-to-face diporphyrins (M = H(2), GaL, Ru(CO)(OH), Co).

The preparation and characterization of a new series of mixed metal cofacial anthracene-bridged diporphyrins (DPA) containing a GaL fragment (L = OMe, OH) and another metallic center (M = GaL, Ru(CO)(OH), Co, and H(2) (i.e. free base)) are reported. The luminescence properties at 298 and 77 K, in degassed EtOH solution, are also reported, and are characterized by a weak pipi fluorescence (2 < tau(F) < 7 ns) arising from the low energy Q-bands (S(1)-->S(0)). In the mixed diporphyrin systems, a strong pipi fluorescence is detected from the free base, while the transition metalloporphyrins of Co(II) and Ru(II) do not emit. The homobimetallic di[Ga(OMe)] species exhibits an unprecedented double (pi)(pi) fluorescence arising from the two lowest energy absorption Q-bands. On the basis of a comparison with photophysical data on GaL monoporphyrins, the weak fluorescence and absence of phosphorescence for most cases indicate efficient intramolecular quenching. To define structural features, the X-ray structures of (DPA)[Ga(OMe)](2) (2), (DPA)[Ga-(OH)-Ru(CO)] (5a), and (DPA)[Ga(OMe)-Ru(MeOH)(CO)] (5b) have been obtained. The structures of 5a and 5b demonstrate an interesting aspect of the structural chemistry of these ligands related to the internal methoxide and methanolic ligands in 5b (resulting in a large interplanar separation and center-to-center distance) and the internal metal-bridging hydroxyl ligand in 5a (resulting in a small interplanar separation and center-to-center distance). These data support previously reported discussions on the ability of the DPA and the DPB analogue (diporphyrinylbiphenylenyl) ligands to open and close their "bite" around the binding pocket between the porphyrin macrocycles.