Photoinduced Inhibition of DNA Amplification by PCR with a Photocisplatin Analog

Abstract

complexes display interesting photophysical and photochemical properties and play an important role in energy and electron transfer processes (Balzani, 2003; Balzani et al., 2008; Balzani et al., 1996, Juris et al., 1988). These complexes have been shown to photocleave DNA via singlet oxygen (1O2) generation (Chouai et al., 2005; Friedman et al., 1990; Grover and Thorp, 1991; Jain et al., 2008; Neyhart et al., 1993). The Metal to Ligand Charge Transfer (3 MLCT) state of these complexes undergoes energy transfer to molecular oxygen (3 O2) to generate 1 O2, which reacts with DNA, cleaving the backbone (Chouai et al., 2005; Friedman et al., 1990; Grover and Thorp, 1991; Jain et al., 2008; Neyhart et al., 1993). Tumors often have low levels of oxygen; therefore, it is necessary to develop PDT agents that operate in the absence of oxygen. Ru(II) polypyridyl complexes with sterically bulky ligands are known as photocisplatin analogs and have been reported to covalently bind with DNA upon irradiation with visible light in the absence of oxygen (Dickerson et al., 2014; Dmytro et al., 2017; Glazer, 2013; Howerton et al., 2012; Kohler et al., 2017; Wachter et al., 2012; Wyland et al., 2017; Albani et al., 2015; Knoll et al., 2014). The bulky ligands lower the energy of the ligand field (3LF) state relative to the 3 MLCT state, thus resulting in photoejection of the ligand (Allen et al., 1984; Caspar and Meyer, 1983; Ford, 1970; Ford, 1982; Garner et al., 2011; Malouf and Ford, 1974). The sterically-strained Ru(II) complexes, [Ru(biq)2(phen)] 2+ and [Ru(biq)(phen)2] 2+, (biq = 2,2’-biquinoline, phen = 1,10-phenanthroline), undergo photoinduced ligand exchange and bind with DNA under hypoxic conditions after excitation by red light (λirr > 600 nm or 650 nm) (Albani et al. 2015). We have recently rePhotoinduced Inhibition of DNA Amplification by PCR with a Photocisplatin Analog