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Photodynamic Therapy (PDT) is a method to selectively kill cancer cells through the absorption of visible light by a photosensitizer. Currently used PDT agents are oxygen-dependent, however, there is a need to develop new drugs that are oxygen-independent. Metal complexes represent a new promising class of PDT agents that can work well in the presence and absence of oxygen.
The complex Pt(dppz)Cl2 (dppz = dipyrido[3,2-a:2´,3´-c]phenazine) was synthesized and characterized, and its DNA binding and photocleavage properties are compared to those of cisplatin, Pt(NH3)2Cl2 and Pt(bpy)Cl2 (bpy = 2,2´-bipyridine). It was shown that Pt(dppz)Cl2 intercalates between the DNA bases, while Pt(NH3)Cl2 and Pt(bpy)Cl2 bind covalently to the duplex. Upon irradiation (λirr > 395 nm) Pt(dppz)Cl2 is able to photocleave plasmid DNA both in air and in the absence of oxygen, resulting in the nicked form. In contrast, cisplatin and Pt(bpy)Cl2 are photochemically inactive towards DNA under these irradiation conditions.
[Rh2(m-O2CCH3)2(R1,R2-dppz)2]2+ (R1 = R2 = NO2, Cl, H, CH3, OCH3, 15-crown-5, 18-crown-6 or R1 = H, R2 = Cl, CH3, OCH3) complexes were also investigated for their photoreactivity toward DNA. The complexes do not intercalate into the DNA duplex, but they cleave DNA upon irradiation with λ > 500 nm. A linear relationship between 1/[DNA]nicked and the free energy |ΔGo| for charge recombination was established. It was also shown that free axial positions are required for dirhodium complexes to be photoactive.
Many ruthenium complexes exhibit DNA light switch behavior, where they are non-emissive in water and become luminescent upon intercalation into the DNA duplex. The emission intensity of [Ru(bpy)2(tpphz)]2+ (tpphz = tetrapyrido[3,2-a:2´,3´-c:3´´, 2´´-h:2´´, 3´´-j] phenazine) and [Ru(bpy)2(taptp)]2+ (taptp = 4,5,9,18-tetraazaphenanthreno[9,10-b] triphenylene) increases by factors 50- and 4-fold upon the addition of DNA, respectively. The emission from intercalated [Ru(bpy)2( tpphz)]2+ is quenched statically in the presence of Co2+ and Zn2+ ions, and the emission can be fully restored by the addition of EDTA. The emission of [Ru(bpy)2(tpphz)]2+ can be reversibly turned ON and OFF over the several cycles. The emission of DNA-intercalated [Ru(bpy)2(taptp)]2+ is not quenched by transition metal ions.
Document number: osu1124238450.
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