Jonathan Ghesquière

What Does the Future Hold for Photo-Oxidizing RuII Complexes with Polyazaaromatic Ligands in Medicinal Chemistry?

Since the discovery of cisplatin, the search for diagnostic or therapeutic agents based on other metals, has expanded intensively owing to the numerous possibilities offered by coordination chemistry. This mini-review focuses on recent advances in the search for Ru(II) polyazaaromatic complexes of potential interest as molecular tools applied to cellular diagnostics or as specific cellular photo-reagents for future biomedical applications. The interaction of Ru(II) polyazaaromatic complexes with living cells is reported, as well as the photo-reaction mechanisms of photo-oxidizing Ru(II) complexes with nucleic acids. The novel strategies currently developed to improve their reactivity and specificity towards DNA, more particularly in the gene-silencing framework, are also discussed.

Photocrosslinking between Peptide–Peptide or Peptide–Oligonucleotide by RuII–TAP Complexes

Ru(II)-TAP complexes have been shown to be very attractive compounds in the frame of developments of new anticancer drugs targeting the genetic material. This increasing interest originates from observations of covalent bond formations, triggered by photo-induced electron transfer (PET) between Ru(II)-TAP complexes and guanine bases of DNA. This photoreaction has recently been extended to the tryptophan (Trp) amino acid for future applications involving peptides. Thus, a double photo-addition of Trp residues of peptides on Ru(II) complexes is demonstrated by mass spectrometry with some structural issues. Such bi-adduct formations offer the possibility of photocrosslinking two Trp-containing biomolecules, which is investigated in this study. Thus, photocrosslinking between two complementary oligonucleotides (ODNs) derivatized by Trp-containing tripeptides is demonstrated by polyacrylamide gel electrophoresis (PAGE) in the presence of Ru(II)-TAP complexes. Both PAGE and MS indicate that such photocrosslinkings arise from two reaction pathways: either via the double addition of Trp residues on the Ru complex or from dimerization of Trp radicals. The competition between these two pathways depends on the experimental conditions. Heterobridgings between guanine bases and tryptophan residues mediated by Ru(II)-TAP complexes is also examined, opening the way to ODN-peptide photocrosslinkings.