Photo-oxidizing RuII complexes and light: Targeting biomolecules via photoadditions

Abstract

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Highly DNA‐Photoreactive Ruthenium 1,4,5,8‐Tetraazaphenanthrene Complex Conjugated to the TAT Peptide: Efficient Vectorization inside HeLa Cells without Phototoxicity – The Importance of Cellular Distribution

“…Indeed, Ru-TAP complexes are very efficient for inducing a PET with the guanine bases of DNA, as shown in several previous studies. [4,28,29] The present results show that the TAT peptide transports the Ru complex mainly into vesicles and into the cytoplasm; therefore, the Ru-TAP complex cannot reach its DNA or RNA targets. In contrast, the Ru-phen complex also transported into the vesicles by the TAT peptide can behave as an excellent singlet-oxygen photosensitizer, which is not the case for the Ru-TAP complex.…”

“…is photoreactive [4] towards the G bases of DNA and gives rise to a PET, as explained in the Introduction. In contrast, [Ru(phen) 3 ] 2+ is not photoreactive towards the G bases.…”

“…[7] In contrast, the use of highly π-deficient ligands such as 1,4,5,8-tetraazaphenanthrene (TAP) or 1,4,5,8,9,12-hexaazatriphenylene (HAT) enhances the photo-oxidizing power of the resulting complex, so that a photoinduced electron transfer (PET) from a guanine (G) base of DNA towards the excited complex leads to luminescence quenching. [4] Interestingly, the recombination of the two radical species generated by this PET process produces an irreversible covalent adduct between the guanine (G) moiety and the Ru II complex (Figure 1, a). [8] Owing to the interest in the study of Ru II complexes in the presence of biomolecules, these metallic compounds were also examined in the presence of living cells to investigate their cellular penetration, intracellular distributions, and interactions with the different cellular components.…”

“…[1][2][3] This increased interest is also due to the photoinduced reactivity of these complexes with the guanine bases of DNA. [4,5] A simple change of ligand coordinated to the metal center allows the properties of the resulting complex to be tailored and, thereby, enables its interaction and photoreactivity with DNA to be tuned. When the extensively studied dipyrido[3,2-a;2′,3′-c]-1 the conjugate was examined by flow cytometry, inductively coupled plasma mass spectrometry (ICP-MS), and confocal imaging microscopy.…”

“…Indeed, as explained above, the Ru-TAP compounds are able to photoinduce irreversible covalent binding of the TAP ligand to the G bases of DNA under visible-light irradiation (Figure 1, a). [4] However, as the naked Ru-TAP complexes cannot cross the cellular membranes, we tethered them to the TAT peptide [sequence (S)GRKKRRQRRR], which corresponds to the 48-57 sequence of the trans-activating transcriptional protein (TAT) of HIV-1.…”