Abstract
Assessment of the DNA photo-oxidation and synthetic photocatalytic activity of chromium polypyridyl complexes is dominated by consideration of their long-lived metal-centered excited states. Here we report the participation of the excited states of [Cr(TMP)2dppz]3+ (1) (TMP = 3,4,7,8-tetramethyl-1,10-phenanthroline; dppz = dipyrido[3,2-a:2′,3′-c]phenazine) in DNA photoreactions. The interactions of enantiomers of 1 with natural DNA or with oligodeoxynucleotides with varying AT content (0–100%) have been studied by steady state UV/visible absorption and luminescence spectroscopic methods, and the emission of 1 is found to be quenched in all systems. The time-resolved infrared (TRIR) and visible absorption spectra (TA) of 1 following excitation in the region between 350 to 400 nm reveal the presence of relatively long-lived dppz-centered states which eventually yield the emissive metal-centered state. The dppz-localized states are fully quenched when bound by GC base pairs and partially so in the presence of an AT base-pair system to generate purine radical cations. The sensitized formation of the adenine radical cation species (A•+T) is identified by assigning the TRIR spectra with help of DFT calculations. In natural DNA and oligodeoxynucleotides containing a mixture of AT and GC of base pairs, the observed time-resolved spectra are consistent with eventual photo-oxidation occurring predominantly at guanine through hole migration between base pairs. The combined targeting of purines leads to enhanced photo-oxidation of guanine. These results show that DNA photo-oxidation by the intercalated 1, which locates the dppz in contact with the target purines, is dominated by the LC centered excited state. This work has implications for future phototherapeutics and photocatalysis.
Highlights
The role of transition metal complexes in causing photooxidation in DNA is well established, and they are increasingly being considered as an alternative to porphyrins for lightactivated therapeutic applications.[1−6] Many of these complexes are expected to generate singlet oxygen which can attack cellular biomolecules, including nucleic acids.[1−6] another possible mechanism, which has become apparent over the past few years, is the direct oxidation of guanine and DNA damage by photoinduced oneelectron abstraction by the excited state of a proximal metal complex.[7−11] In order to facilitate such a reaction with DNA one can incorporate ligands that will cause the complex to bind strongly to DNA with well-defined geometry
While the 2MC state is expected to participate in photo-oxidation observed in the case of diffusional quenching, when 1 is intercalated the preorganization of the dppz ligand adjacent to Watson Crick base pairs facilitates photo-oxidation to be dominated by the LC state, circumventing the 2MC state
In mixed DNA systems binding at an AT site likely leads to hole migration to form the guanine radical cation
Summary
The role of transition metal complexes in causing photooxidation in DNA is well established, and they are increasingly being considered as an alternative to porphyrins for lightactivated therapeutic applications.[1−6] Many (perhaps most) of these complexes are expected to generate singlet oxygen which can attack cellular biomolecules, including nucleic acids.[1−6] another possible mechanism, which has become apparent over the past few years, is the direct oxidation of guanine and DNA damage by photoinduced oneelectron abstraction by the excited state of a proximal metal complex.[7−11] In order to facilitate such a reaction with DNA one can incorporate ligands that will cause the complex to bind strongly to DNA with well-defined geometry This can be achieved using complexes containing a ligand which can intercalate between the base pairs of DNA. Such LC states are expected to be of significantly higher energy than the long-lived LC ππ* triplet state observed for ruthenium complexes containing the extended dppn
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